fentanyl transdermal (Rx)

Chronic Severe Pain

Indicated for chronic pain in opioid-tolerant patients, severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate

Discontinue or taper all other extended-release opioids when beginning fentanyl transdermal therapy

25-100 mcg/hr, reapplied q72hr until adequate analgesia is achieved

Also see Administration

Opioid-tolerant definition

• Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day morphine, 25 mcg/day transdermal fentanyl, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO oxymorphone, 60 mg/day PO hydrocodone, or an equianalgesic dose of another opioid

Dosage Modifications

Hepatic impairment

• Mild-to-moderate (Child Pugh A to B): Start with one half of the usual dose; closely monitor for signs of respiratory and central nervous system depression (see Cautions)
• Severe (Child C): Avoid use

Renal impairment

• Mild-to-moderate: Start with one half of the usual dose; closely monitor for signs of respiratory and central nervous system depression (see Cautions)
• Severe: Avoid use

Dosing Considerations

Limitations of use

• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain

Conversion oral/IV opioids to fentanyl transdermal

• Each transdermal system is worn continuously for up to 72 hr (see Administration)
• Tables found in prescribing information cannot be used to convert from fentanyl transdermal to another opioid because conversions will result in an overestimation of the dose of new opioid and may result in fatal overdosage
• Calculate 24-hr morphine dose and find the corresponding recommended initial fentanyl transdermal dose
• Initiate recommended dose and titrate dose no more frequently than 3 days after initial dose and every 6 days thereafter until analgesic efficacy is attained
• For patients that require >100 mcg/hr, several transdermal systems may be used

Discontinuation of fentanyl transdermal

• Significant amounts of fentanyl continue to be absorbed from the skin for ≥24 hr after the patch is removed

• Convert to another opioid

  • Remove transdermal and titrate dose of new analgesic based upon patient’s report of pain until adequate analgesia has been attained
  • Upon system removal, ≥17 hr are required for a 50% decrease in serum fentanyl concentrations
  • Withdrawal symptoms are possible in some patients after conversion or dose adjustment

• Not converting to another opioid

  • Gradually titrate the dose, (eg, 50% dosage reduction q6days), while monitoring carefully for signs and symptoms of withdrawal
  • If patient develops these signs or symptoms, raise dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both
  • Do not abruptly discontinue fentanyl patch It is unknown at what dose level the fentanyl transdermal may be discontinued without producing the signs and symptoms of opioid withdrawal

Access to naloxone for opioid overdose

• Assess need for naloxone upon initiating and renewing treatment

• Consider prescribing naloxone

  • Based on patient’s risk factors for overdose (eg, concomitant use of CNS depressants, a history of opioid use disorder, prior opioid overdose); presence of risk factors should not prevent proper pain management
  • Household members (including children) or other close contacts at risk for accidental ingestion or overdose

• Consult patients and caregivers on the following:

  • Availability of naloxone for emergency treatment of opioid overdose
  • Ways differ on how to obtain naloxone as permitted by individual state dispensing and prescribing requirements or guidelines (eg, by prescription, directly from a pharmacist, as part of a community-based program)

Chronic Pain (Off-label)

Treatment of chronic pain in children who are opioid-tolerant and receiving ≥60 mg/day PO of morphine or equivalent

<2 years: Safety not established

≥2 years: 25-100 mcg/hr, reapplied q72hr until adequate analgesia is achieved

Dosing Considerations

Limitations of use

• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain

Conversion oral/IV opioids to fentanyl transdermal

• Each transdermal system is worn continuously for up to 72 hr (see Administration)
• Tables found in prescribing information cannot be used to convert from fentanyl transdermal to another opioid because conversions will result in an overestimation of the dose of new opioid and may result in fatal overdosage
• Calculate 24-hr morphine dose and find the corresponding recommended initial fentanyl transdermal dose
• Initiate recommended dose and titrate dose no more frequently than 3 days after initial dose and every 6 days thereafter until analgesic efficacy is attained
• For patients that require >100 mcg/hr, several transdermal systems may be used

Discontinuation of fentanyl transdermal

• Significant amounts of fentanyl continue to be absorbed from the skin for ≥24 hr after the patch is removed

• Convert to another opioid

  • Remove transdermal and titrate dose of new analgesic based upon patient’s report of pain until adequate analgesia has been attained
  • Upon system removal, ≥17 hr are required for a 50% decrease in serum fentanyl concentrations
  • Withdrawal symptoms are possible in some patients after conversion or dose adjustment

• Not converting to another opioid

  • Gradually titrate the dose, (eg, 50% dosage reduction q6days), while monitoring carefully for signs and symptoms of withdrawal
  • If patient develops these signs or symptoms, raise dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both
  • Do not abruptly discontinue fentanyl patch It is unknown at what dose level the fentanyl transdermal may be discontinued without producing the signs and symptoms of opioid withdrawal

Contraindicated (9)

• alvimopan

  alvimopan, fentanyl transdermal. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

• isocarboxazid

  isocarboxazid increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

• phenelzine

  phenelzine increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

• rasagiline

  rasagiline increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. .

• safinamide

  fentanyl transdermal, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

• selegiline

  selegiline increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. .

• selegiline transdermal

  selegiline transdermal increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. .

• thalidomide

  fentanyl transdermal and thalidomide both increase sedation. Contraindicated.

• tranylcypromine

  tranylcypromine increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

Serious - Use Alternative (192)

• acrivastine

  acrivastine and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• alfentanil

  fentanyl transdermal and alfentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• alprazolam

  fentanyl transdermal and alprazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• amiodarone

  amiodarone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• amisulpride

  amisulpride and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• amitriptyline

  fentanyl transdermal and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• amobarbital

  fentanyl transdermal, amobarbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  amobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.
  
  fentanyl transdermal and amobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• apalutamide

  apalutamide will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  aprepitant will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• asenapine

  asenapine and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• asenapine transdermal

  asenapine transdermal and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• atazanavir

  atazanavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• atracurium

  fentanyl transdermal, atracurium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• avapritinib

  avapritinib and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• baclofen

  fentanyl transdermal and baclofen both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  benzhydrocodone/acetaminophen and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bicalutamide

  bicalutamide will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• brexpiprazole

  brexpiprazole and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brigatinib

  brigatinib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.

• brimonidine

  brimonidine and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brivaracetam

  brivaracetam and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine

  fentanyl transdermal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  buprenorphine decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine buccal

  buprenorphine buccal decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal, buprenorphine buccal. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and buprenorphine buccal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine subdermal implant

  buprenorphine subdermal implant and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  fentanyl transdermal, buprenorphine transdermal. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  buprenorphine transdermal and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• butabarbital

  fentanyl transdermal, butabarbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and butabarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• butalbital

  fentanyl transdermal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• butorphanol

  fentanyl transdermal, butorphanol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  butorphanol decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal and butorphanol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• carisoprodol

  fentanyl transdermal and carisoprodol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• chloral hydrate

  fentanyl transdermal, chloral hydrate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• chlordiazepoxide

  fentanyl transdermal and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• chlorpheniramine

  fentanyl transdermal and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• chlorpromazine

  fentanyl transdermal, chlorpromazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and chlorpromazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• chlorzoxazone

  fentanyl transdermal and chlorzoxazone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• cimetidine

  cimetidine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• cisatracurium

  fentanyl transdermal, cisatracurium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• citalopram

  fentanyl transdermal, citalopram. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• clarithromycin

  clarithromycin will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• clobazam

  fentanyl transdermal and clobazam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• clomipramine

  fentanyl transdermal and clomipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• clonazepam

  fentanyl transdermal and clonazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• clorazepate

  fentanyl transdermal and clorazepate both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• cobicistat

  cobicistat will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• codeine

  fentanyl transdermal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• conivaptan

  conivaptan will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• crizotinib

  crizotinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• cyclobenzaprine

  fentanyl transdermal and cyclobenzaprine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• cyclosporine

  cyclosporine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• dantrolene

  fentanyl transdermal and dantrolene both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• desflurane

  fentanyl transdermal, desflurane. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and desflurane both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• desipramine

  fentanyl transdermal and desipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• diazepam

  fentanyl transdermal and diazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• diazepam intranasal

  diazepam intranasal, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• doxepin

  fentanyl transdermal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• doxycycline

  doxycycline will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• doxylamine

  fentanyl transdermal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• dronedarone

  dronedarone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• droperidol

  fentanyl transdermal and droperidol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• eluxadoline

  fentanyl transdermal, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

• erythromycin base

  erythromycin base will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• escitalopram

  fentanyl transdermal, escitalopram. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• estazolam

  fentanyl transdermal, estazolam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and estazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• eszopiclone

  fentanyl transdermal, eszopiclone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• ethanol

  fentanyl transdermal, ethanol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• etomidate

  fentanyl transdermal, etomidate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• etravirine

  etravirine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• fentanyl

  fentanyl and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl intranasal

  fentanyl intranasal and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl iontophoretic transdermal system

  fentanyl iontophoretic transdermal system and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fexinidazole

  fexinidazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fluconazole

  fluconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fluoxetine

  fentanyl transdermal, fluoxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• fluphenazine

  fentanyl transdermal, fluphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• flurazepam

  fentanyl transdermal, flurazepam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and flurazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fluvoxamine

  fluvoxamine and fentanyl transdermal both increase serotonin levels. Avoid or Use Alternate Drug.

• fosamprenavir

  fosamprenavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fosaprepitant

  fosaprepitant will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fosphenytoin

  fosphenytoin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• gabapentin

  fentanyl transdermal and gabapentin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• grapefruit

  grapefruit will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• haloperidol

  fentanyl transdermal, haloperidol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  haloperidol will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• hydrocodone

  hydrocodone, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  fentanyl transdermal and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• hydromorphone

  fentanyl transdermal, hydromorphone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and hydromorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• hydroxyzine

  fentanyl transdermal and hydroxyzine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• idelalisib

  idelalisib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• iloperidone

  iloperidone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• imatinib

  imatinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• imipramine

  fentanyl transdermal and imipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• indinavir

  indinavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• isoflurane

  fentanyl transdermal, isoflurane. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and isoflurane both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• isoniazid

  isoniazid will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• itraconazole

  itraconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole. If coadministration with fentanyl is necessary, closely monitor for respiratory depression and sedation and consider fentanyl dose adjustments until stable drug effects are achieved.

• ivosidenib

  ivosidenib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketamine

  fentanyl transdermal, ketamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• lapatinib

  lapatinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• levorphanol

  fentanyl transdermal, levorphanol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• lidocaine

  lidocaine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• linezolid

  fentanyl transdermal, linezolid. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• lonafarnib

  fentanyl transdermal will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• loperamide

  fentanyl transdermal, loperamide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• lopinavir

  lopinavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• lorazepam

  fentanyl transdermal and lorazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• loxapine

  fentanyl transdermal, loxapine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• loxapine inhaled

  fentanyl transdermal, loxapine inhaled. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• lumacaftor/ivacaftor

  lumacaftor/ivacaftor will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.

• maprotiline

  fentanyl transdermal and maprotiline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• meperidine

  fentanyl transdermal, meperidine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• metaxalone

  fentanyl transdermal and metaxalone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methadone

  fentanyl transdermal, methadone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and methadone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methocarbamol

  fentanyl transdermal and methocarbamol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methohexital

  fentanyl transdermal, methohexital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and methohexital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• metoclopramide intranasal

  fentanyl transdermal, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metronidazole

  metronidazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• midazolam

  fentanyl transdermal and midazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• mifepristone

  mifepristone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Monitor patients for respiratory depression and sedation at frequent intervals if coadministration of CYP3A4 inhibitors with fentanyl is necessary, and consider fentanyl dose adjustments until stable drug effects achieved

• mirtazapine

  fentanyl transdermal and mirtazapine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• mobocertinib

  mobocertinib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.

• morphine

  fentanyl transdermal, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and morphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• nalbuphine

  fentanyl transdermal, nalbuphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  nalbuphine decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal and nalbuphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• nefazodone

  nefazodone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• nelfinavir

  nelfinavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• netupitant/palonosetron

  netupitant/palonosetron will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• nicardipine

  nicardipine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• nortriptyline

  fentanyl transdermal and nortriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• oliceridine

  fentanyl transdermal and oliceridine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• olopatadine intranasal

  fentanyl transdermal and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• olutasidenib

  olutasidenib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.

• opium tincture

  fentanyl transdermal, opium tincture. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• orphenadrine

  fentanyl transdermal and orphenadrine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• oxazepam

  fentanyl transdermal and oxazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• oxycodone

  fentanyl transdermal, oxycodone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• oxymorphone

  fentanyl transdermal, oxymorphone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and oxymorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• ozanimod

  ozanimod and fentanyl transdermal both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• pancuronium

  fentanyl transdermal, pancuronium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• paroxetine

  fentanyl transdermal, paroxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• pentazocine

  fentanyl transdermal, pentazocine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  pentazocine decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal and pentazocine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• pentobarbital

  fentanyl transdermal, pentobarbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and pentobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• perphenazine

  fentanyl transdermal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• pheniramine

  fentanyl transdermal and pheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• phenobarbital

  fentanyl transdermal and phenobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• pimozide

  fentanyl transdermal, pimozide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• posaconazole

  posaconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• pregabalin

  fentanyl transdermal and pregabalin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• prochlorperazine

  fentanyl transdermal, prochlorperazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and prochlorperazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• promethazine

  fentanyl transdermal and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• propofol

  fentanyl transdermal, propofol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and propofol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• protriptyline

  fentanyl transdermal and protriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• quazepam

  fentanyl transdermal, quazepam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and quazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• quetiapine

  fentanyl transdermal and quetiapine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• quinidine

  quinidine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• ramelteon

  fentanyl transdermal, ramelteon. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• remifentanil

  fentanyl transdermal, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• ritonavir

  ritonavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• rocuronium

  fentanyl transdermal, rocuronium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• saquinavir

  saquinavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• scopolamine

  fentanyl transdermal and scopolamine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• secobarbital

  fentanyl transdermal, secobarbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• selinexor

  selinexor, fentanyl transdermal. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• sertraline

  sertraline will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.
  
  fentanyl transdermal, sertraline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• sevoflurane

  fentanyl transdermal, sevoflurane. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and sevoflurane both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• sotorasib

  sotorasib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

• succinylcholine

  fentanyl transdermal, succinylcholine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• sufentanil

  fentanyl transdermal, sufentanil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• sufentanil SL

  fentanyl transdermal, sufentanil SL. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  sufentanil SL, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• suvorexant

  fentanyl transdermal, suvorexant. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• tapentadol

  fentanyl transdermal, tapentadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and tapentadol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• tasimelteon

  fentanyl transdermal, tasimelteon. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• temazepam

  fentanyl transdermal, temazepam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and temazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• tetrabenazine

  fentanyl transdermal and tetrabenazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• tetracycline

  tetracycline will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• thioridazine

  fentanyl transdermal, thioridazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and thioridazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• thiothixene

  fentanyl transdermal, thiothixene. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• ticagrelor

  ticagrelor will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• tipranavir

  tipranavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• tizanidine

  fentanyl transdermal and tizanidine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• tramadol

  fentanyl transdermal, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and tramadol both increase sedation. Avoid or Use Alternate Drug.

• triazolam

  fentanyl transdermal, triazolam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and triazolam both increase sedation. Avoid or Use Alternate Drug.

• trifluoperazine

  fentanyl transdermal, trifluoperazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• tucatinib

  tucatinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• valerian

  valerian and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug.

• vecuronium

  fentanyl transdermal, vecuronium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• verapamil

  verapamil will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• voriconazole

  voriconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• vortioxetine

  fentanyl transdermal, vortioxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• voxelotor

  voxelotor will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• zaleplon

  fentanyl transdermal, zaleplon. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• zileuton

  zileuton will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• zolpidem

  fentanyl transdermal, zolpidem. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

Monitor Closely (167)

• acetaminophen/phenyltoloxamine

  fentanyl transdermal and acetaminophen/phenyltoloxamine both increase sedation. Use Caution/Monitor.

• amiloride

  fentanyl transdermal decreases effects of amiloride by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• amoxapine

  fentanyl transdermal and amoxapine both increase sedation. Use Caution/Monitor.

• aripiprazole

  fentanyl transdermal and aripiprazole both increase sedation. Use Caution/Monitor.

• asenapine transdermal

  fentanyl transdermal and asenapine transdermal both increase sedation. Use Caution/Monitor.

• atogepant

  fentanyl transdermal will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atropine

  fentanyl transdermal, atropine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• avapritinib

  fentanyl transdermal will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• belzutifan

  belzutifan will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• bendroflumethiazide

  fentanyl transdermal decreases effects of bendroflumethiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• bosentan

  bosentan will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• brexanolone

  brexanolone, fentanyl transdermal. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brompheniramine

  fentanyl transdermal, brompheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and brompheniramine both increase sedation. Use Caution/Monitor.

• bumetanide

  fentanyl transdermal decreases effects of bumetanide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• buprenorphine, long-acting injection

  fentanyl transdermal increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.

• carbamazepine

  carbamazepine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• carbinoxamine

  fentanyl transdermal, carbinoxamine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and carbinoxamine both increase sedation. Use Caution/Monitor.

• cariprazine

  fentanyl transdermal and cariprazine both increase sedation. Use Caution/Monitor.

• cenobamate

  cenobamate will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
  
  cenobamate, fentanyl transdermal. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  ceritinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• cetirizine

  fentanyl transdermal and cetirizine both increase sedation. Use Caution/Monitor.

• chloramphenicol

  chloramphenicol will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• chlorothiazide

  fentanyl transdermal decreases effects of chlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• chlorpheniramine

  fentanyl transdermal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• chlorthalidone

  fentanyl transdermal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• clemastine

  fentanyl transdermal, clemastine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and clemastine both increase sedation. Use Caution/Monitor.

• clonidine

  fentanyl transdermal and clonidine both increase sedation. Use Caution/Monitor.

• clozapine

  fentanyl transdermal and clozapine both increase sedation. Use Caution/Monitor.

• cyproheptadine

  fentanyl transdermal, cyproheptadine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and cyproheptadine both increase sedation. Use Caution/Monitor.

• dabrafenib

  dabrafenib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• daridorexant

  fentanyl transdermal and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darunavir

  darunavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• deutetrabenazine

  fentanyl transdermal and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexamethasone

  dexamethasone will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• dexbrompheniramine

  fentanyl transdermal and dexbrompheniramine both increase sedation. Use Caution/Monitor.

• dexchlorpheniramine

  fentanyl transdermal, dexchlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and dexchlorpheniramine both increase sedation. Use Caution/Monitor.

• dichlorphenamide

  dichlorphenamide and fentanyl transdermal both decrease serum potassium. Use Caution/Monitor.

• difelikefalin

  difelikefalin and fentanyl transdermal both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  fentanyl transdermal and difenoxin hcl both increase sedation. Use Caution/Monitor.

• diltiazem

  diltiazem will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• dimenhydrinate

  fentanyl transdermal, dimenhydrinate. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and dimenhydrinate both increase sedation. Use Caution/Monitor.

• diphenhydramine

  fentanyl transdermal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and diphenhydramine both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  fentanyl transdermal and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• doxylamine

  fentanyl transdermal and doxylamine both increase sedation. Use Caution/Monitor.

• duvelisib

  duvelisib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

• efavirenz

  efavirenz will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.
  
  fentanyl transdermal and efavirenz both increase sedation. Use Caution/Monitor.

• elagolix

  elagolix decreases levels of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• elranatamab

  elranatamab will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• eluxadoline

  eluxadoline increases levels of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.

• encorafenib

  encorafenib, fentanyl transdermal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• entacapone

  fentanyl transdermal and entacapone both increase sedation. Use Caution/Monitor.

• enzalutamide

  enzalutamide will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• epcoritamab

  epcoritamab, fentanyl transdermal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

• esketamine intranasal

  esketamine intranasal, fentanyl transdermal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• eszopiclone

  fentanyl transdermal and eszopiclone both increase sedation. Use Caution/Monitor.

• ethacrynic acid

  fentanyl transdermal decreases effects of ethacrynic acid by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• ethanol

  fentanyl transdermal and ethanol both increase sedation. Use Caution/Monitor.

• ethosuximide

  fentanyl transdermal and ethosuximide both increase sedation. Use Caution/Monitor.

• ethotoin

  fentanyl transdermal and ethotoin both increase sedation. Use Caution/Monitor.

• fedratinib

  fedratinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felbamate

  fentanyl transdermal and felbamate both increase sedation. Use Caution/Monitor.

• fenfluramine

  fentanyl transdermal and fenfluramine both increase sedation. Use Caution/Monitor.

• fexofenadine

  fentanyl transdermal and fexofenadine both increase sedation. Use Caution/Monitor.

• finerenone

  fentanyl transdermal will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

• flibanserin

  fentanyl transdermal and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluphenazine

  fentanyl transdermal and fluphenazine both increase sedation. Use Caution/Monitor.

• furosemide

  fentanyl transdermal decreases effects of furosemide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• gabapentin

  gabapentin, fentanyl transdermal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  gabapentin enacarbil, fentanyl transdermal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• ganaxolone

  fentanyl transdermal and ganaxolone both increase sedation. Use Caution/Monitor.

• glofitamab

  glofitamab, fentanyl transdermal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

• guanfacine

  fentanyl transdermal and guanfacine both increase sedation. Use Caution/Monitor.

• guselkumab

  guselkumab, fentanyl transdermal. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• haloperidol

  fentanyl transdermal and haloperidol both increase sedation. Use Caution/Monitor.

• hydrochlorothiazide

  fentanyl transdermal decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• hydroxyzine

  fentanyl transdermal, hydroxyzine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• iloperidone

  fentanyl transdermal and iloperidone both increase sedation. Use Caution/Monitor.

• indapamide

  fentanyl transdermal decreases effects of indapamide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• isavuconazonium sulfate

  fentanyl transdermal will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  isavuconazonium sulfate will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• istradefylline

  istradefylline will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• ketamine

  fentanyl transdermal and ketamine both increase sedation. Use Caution/Monitor.

• ketoconazole

  ketoconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• ketotifen, drug-eluting contact lens

  fentanyl transdermal and ketotifen, drug-eluting contact lens both increase sedation. Use Caution/Monitor.

• lamotrigine

  fentanyl transdermal and lamotrigine both increase sedation. Use Caution/Monitor.

• larotrectinib

  larotrectinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• lasmiditan

  lasmiditan, fentanyl transdermal. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• lemborexant

  fentanyl transdermal will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
  
  lemborexant, fentanyl transdermal. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• lenacapavir

  lenacapavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Carefully monitor the therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with coadministration.

• levetiracetam

  fentanyl transdermal and levetiracetam both increase sedation. Use Caution/Monitor.

• levocetirizine

  fentanyl transdermal and levocetirizine both increase sedation. Use Caution/Monitor.

• levoketoconazole

  levoketoconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• levorphanol

  fentanyl transdermal and levorphanol both increase sedation. Use Caution/Monitor.

• loratadine

  fentanyl transdermal and loratadine both increase sedation. Use Caution/Monitor.

• lorlatinib

  lorlatinib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• loxapine

  fentanyl transdermal and loxapine both increase sedation. Use Caution/Monitor.

• lumateperone

  fentanyl transdermal and lumateperone both increase sedation. Use Caution/Monitor.

• lurasidone

  fentanyl transdermal and lurasidone both increase sedation. Use Caution/Monitor.

• meclizine

  fentanyl transdermal and meclizine both increase sedation. Use Caution/Monitor.

• meperidine

  fentanyl transdermal and meperidine both increase sedation. Use Caution/Monitor.

• meprobamate

  fentanyl transdermal and meprobamate both increase sedation. Use Caution/Monitor.

• methsuximide

  fentanyl transdermal and methsuximide both increase sedation. Use Caution/Monitor.

• methyclothiazide

  fentanyl transdermal decreases effects of methyclothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• metolazone

  fentanyl transdermal decreases effects of metolazone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• midazolam intranasal

  midazolam intranasal, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• mitotane

  mitotane will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• molindone

  fentanyl transdermal and molindone both increase sedation. Use Caution/Monitor.

• nafcillin

  nafcillin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• nevirapine

  nevirapine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• nitrous oxide

  fentanyl transdermal and nitrous oxide both increase sedation. Use Caution/Monitor.

• olanzapine

  fentanyl transdermal and olanzapine both increase sedation. Use Caution/Monitor.

• oliceridine

  oliceridine, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• opicapone

  fentanyl transdermal and opicapone both increase sedation. Use Caution/Monitor.

• opium tincture

  fentanyl transdermal and opium tincture both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  oxcarbazepine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• paliperidone

  fentanyl transdermal and paliperidone both increase sedation. Use Caution/Monitor.

• pentobarbital

  pentobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• perampanel

  fentanyl transdermal and perampanel both increase sedation. Use Caution/Monitor.

• perphenazine

  fentanyl transdermal and perphenazine both increase sedation. Use Caution/Monitor.

• phenobarbital

  phenobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• phenytoin

  phenytoin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• pimozide

  fentanyl transdermal and pimozide both increase sedation. Use Caution/Monitor.

• pomalidomide

  fentanyl transdermal and pomalidomide both increase sedation. Use Caution/Monitor.

• pregabalin

  pregabalin, fentanyl transdermal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• primidone

  primidone will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.
  
  fentanyl transdermal and primidone both increase sedation. Use Caution/Monitor.

• promethazine

  fentanyl transdermal, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• pyrilamine

  fentanyl transdermal and pyrilamine both increase sedation. Use Caution/Monitor.

• ramelteon

  fentanyl transdermal and ramelteon both increase sedation. Use Caution/Monitor.

• remifentanil

  fentanyl transdermal and remifentanil both increase sedation. Use Caution/Monitor.

• remimazolam

  remimazolam, fentanyl transdermal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• reserpine

  fentanyl transdermal and reserpine both increase sedation. Use Caution/Monitor.

• ribociclib

  ribociclib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

• rifabutin

  rifabutin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• rifampin

  rifampin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• rifapentine

  rifapentine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• risperidone

  fentanyl transdermal and risperidone both increase sedation. Use Caution/Monitor.

• ropeginterferon alfa 2b

  ropeginterferon alfa 2b will increase the level or effect of fentanyl transdermal by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.

• rucaparib

  rucaparib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• schisandra

  schisandra will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• secobarbital

  secobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects; May also enhance CNS depressant effect of fentanyl

• sodium oxybate

  fentanyl transdermal and sodium oxybate both increase sedation. Use Caution/Monitor.

• spironolactone

  fentanyl transdermal decreases effects of spironolactone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• St John's Wort

  St John's Wort will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• stiripentol

  stiripentol, fentanyl transdermal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  fentanyl transdermal and stiripentol both increase sedation. Use Caution/Monitor.

• sufentanil

  fentanyl transdermal and sufentanil both increase sedation. Use Caution/Monitor.

• sufentanil SL

  fentanyl transdermal and sufentanil SL both increase sedation. Use Caution/Monitor.

• suvorexant

  fentanyl transdermal and suvorexant both increase sedation. Use Caution/Monitor.

• talquetamab

  talquetamab will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• tasimelteon

  fentanyl transdermal and tasimelteon both increase sedation. Use Caution/Monitor.

• tazemetostat

  tazemetostat will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  tecovirimat will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• thiothixene

  fentanyl transdermal and thiothixene both increase sedation. Use Caution/Monitor.

• tiagabine

  fentanyl transdermal and tiagabine both increase sedation. Use Caution/Monitor.

• tolcapone

  fentanyl transdermal and tolcapone both increase sedation. Use Caution/Monitor.

• topiramate

  fentanyl transdermal and topiramate both increase sedation. Use Caution/Monitor.

• torsemide

  fentanyl transdermal decreases effects of torsemide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• trazodone

  fentanyl transdermal and trazodone both increase sedation. Use Caution/Monitor.

• triamterene

  fentanyl transdermal decreases effects of triamterene by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• trifluoperazine

  fentanyl transdermal and trifluoperazine both increase sedation. Use Caution/Monitor.

• triprolidine

  fentanyl transdermal, triprolidine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and triprolidine both increase sedation. Use Caution/Monitor.

• valproic acid

  fentanyl transdermal and valproic acid both increase sedation. Use Caution/Monitor.

• vigabatrin

  fentanyl transdermal and vigabatrin both increase sedation. Use Caution/Monitor.

• zaleplon

  fentanyl transdermal and zaleplon both increase sedation. Use Caution/Monitor.

• ziconotide

  fentanyl transdermal and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  fentanyl transdermal and ziprasidone both increase sedation. Use Caution/Monitor.

• zolpidem

  fentanyl transdermal and zolpidem both increase sedation. Use Caution/Monitor.

• zonisamide

  fentanyl transdermal and zonisamide both increase sedation. Use Caution/Monitor.

Minor (3)

• acetazolamide

  acetazolamide will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• anastrozole

  anastrozole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclophosphamide

  cyclophosphamide will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acetaminophen/phenyltoloxamine

  Monitor Closely (1)fentanyl transdermal and acetaminophen/phenyltoloxamine both increase sedation. Use Caution/Monitor.

• acetazolamide

  Minor (1)acetazolamide will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• acrivastine

  Serious - Use Alternative (1)acrivastine and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• alfentanil

  Serious - Use Alternative (1)fentanyl transdermal and alfentanil both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• alprazolam

  Serious - Use Alternative (1)fentanyl transdermal and alprazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• alvimopan

  Contraindicated (1)alvimopan, fentanyl transdermal. receptor binding competition. Contraindicated. Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea. No significant interaction is expected with concurrent use of opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or fewer consecutive days prior to alvimopan.

• amiloride

  Monitor Closely (1)fentanyl transdermal decreases effects of amiloride by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• amiodarone

  Serious - Use Alternative (1)amiodarone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• amisulpride

  Serious - Use Alternative (1)amisulpride and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• amitriptyline

  Serious - Use Alternative (1)fentanyl transdermal and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• amobarbital

  Serious - Use Alternative (3)amobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.
  
  fentanyl transdermal, amobarbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and amobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• amoxapine

  Monitor Closely (1)fentanyl transdermal and amoxapine both increase sedation. Use Caution/Monitor.

• anastrozole

  Minor (1)anastrozole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

• aprepitant

  Serious - Use Alternative (1)aprepitant will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• aripiprazole

  Monitor Closely (1)fentanyl transdermal and aripiprazole both increase sedation. Use Caution/Monitor.

• asenapine

  Serious - Use Alternative (1)asenapine and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• asenapine transdermal

  Monitor Closely (1)fentanyl transdermal and asenapine transdermal both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine transdermal and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• atazanavir

  Serious - Use Alternative (1)atazanavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• atogepant

  Monitor Closely (1)fentanyl transdermal will increase the level or effect of atogepant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atracurium

  Serious - Use Alternative (1)fentanyl transdermal, atracurium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• atropine

  Monitor Closely (1)fentanyl transdermal, atropine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• avapritinib

  Monitor Closely (1)fentanyl transdermal will increase the level or effect of avapritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)avapritinib and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• baclofen

  Serious - Use Alternative (1)fentanyl transdermal and baclofen both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• belzutifan

  Monitor Closely (1)belzutifan will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

• bendroflumethiazide

  Monitor Closely (1)fentanyl transdermal decreases effects of bendroflumethiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (2)benzhydrocodone/acetaminophen, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  benzhydrocodone/acetaminophen and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bicalutamide

  Serious - Use Alternative (1)bicalutamide will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• bosentan

  Monitor Closely (1)bosentan will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• brexanolone

  Monitor Closely (1)brexanolone, fentanyl transdermal. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Serious - Use Alternative (1)brexpiprazole and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brigatinib

  Serious - Use Alternative (1)brigatinib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Brigatinib induces CYP3A4 in vitro. Coadministration with CYP3A4 substrates, particularly those with a narrow therapeutic index, can result in decreased concentrations and loss of efficacy. If unable to avoid coadministration, monitor CYP3A4 substrate levels and adjust dose as needed.

• brimonidine

  Serious - Use Alternative (1)brimonidine and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brivaracetam

  Serious - Use Alternative (1)brivaracetam and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brompheniramine

  Monitor Closely (2)fentanyl transdermal, brompheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and brompheniramine both increase sedation. Use Caution/Monitor.

• bumetanide

  Monitor Closely (1)fentanyl transdermal decreases effects of bumetanide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• buprenorphine

  Serious - Use Alternative (3)fentanyl transdermal, buprenorphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  buprenorphine decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal and buprenorphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine buccal

  Serious - Use Alternative (3)buprenorphine buccal decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal, buprenorphine buccal. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and buprenorphine buccal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine subdermal implant

  Serious - Use Alternative (1)buprenorphine subdermal implant and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  Serious - Use Alternative (2)fentanyl transdermal, buprenorphine transdermal. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  buprenorphine transdermal and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (1)fentanyl transdermal increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.Serious - Use Alternative (1)buprenorphine, long-acting injection and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• butabarbital

  Serious - Use Alternative (2)fentanyl transdermal, butabarbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and butabarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• butalbital

  Serious - Use Alternative (2)fentanyl transdermal, butalbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and butalbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• butorphanol

  Serious - Use Alternative (3)fentanyl transdermal, butorphanol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  butorphanol decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal and butorphanol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• carbamazepine

  Monitor Closely (1)carbamazepine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• carbinoxamine

  Monitor Closely (2)fentanyl transdermal, carbinoxamine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and carbinoxamine both increase sedation. Use Caution/Monitor.

• cariprazine

  Monitor Closely (1)fentanyl transdermal and cariprazine both increase sedation. Use Caution/Monitor.

• carisoprodol

  Serious - Use Alternative (1)fentanyl transdermal and carisoprodol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• cenobamate

  Monitor Closely (2)cenobamate, fentanyl transdermal. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• ceritinib

  Monitor Closely (1)ceritinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• cetirizine

  Monitor Closely (1)fentanyl transdermal and cetirizine both increase sedation. Use Caution/Monitor.

• chloral hydrate

  Serious - Use Alternative (1)fentanyl transdermal, chloral hydrate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• chloramphenicol

  Monitor Closely (1)chloramphenicol will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• chlordiazepoxide

  Serious - Use Alternative (1)fentanyl transdermal and chlordiazepoxide both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• chlorothiazide

  Monitor Closely (1)fentanyl transdermal decreases effects of chlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• chlorpheniramine

  Monitor Closely (1)fentanyl transdermal, chlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.Serious - Use Alternative (1)fentanyl transdermal and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• chlorpromazine

  Serious - Use Alternative (2)fentanyl transdermal, chlorpromazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and chlorpromazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• chlorthalidone

  Monitor Closely (1)fentanyl transdermal decreases effects of chlorthalidone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• chlorzoxazone

  Serious - Use Alternative (1)fentanyl transdermal and chlorzoxazone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• cimetidine

  Serious - Use Alternative (1)cimetidine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• cisatracurium

  Serious - Use Alternative (1)fentanyl transdermal, cisatracurium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• citalopram

  Serious - Use Alternative (1)fentanyl transdermal, citalopram. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• clarithromycin

  Serious - Use Alternative (1)clarithromycin will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• clemastine

  Monitor Closely (2)fentanyl transdermal, clemastine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and clemastine both increase sedation. Use Caution/Monitor.

• clobazam

  Serious - Use Alternative (1)fentanyl transdermal and clobazam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• clomipramine

  Serious - Use Alternative (1)fentanyl transdermal and clomipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• clonazepam

  Serious - Use Alternative (1)fentanyl transdermal and clonazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• clonidine

  Monitor Closely (1)fentanyl transdermal and clonidine both increase sedation. Use Caution/Monitor.

• clorazepate

  Serious - Use Alternative (1)fentanyl transdermal and clorazepate both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• clozapine

  Monitor Closely (1)fentanyl transdermal and clozapine both increase sedation. Use Caution/Monitor.

• cobicistat

  Serious - Use Alternative (1)cobicistat will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• codeine

  Serious - Use Alternative (2)fentanyl transdermal, codeine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• conivaptan

  Serious - Use Alternative (1)conivaptan will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• crizotinib

  Serious - Use Alternative (1)crizotinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• cyclobenzaprine

  Serious - Use Alternative (1)fentanyl transdermal and cyclobenzaprine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• cyclophosphamide

  Minor (1)cyclophosphamide will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• cyclosporine

  Serious - Use Alternative (1)cyclosporine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• cyproheptadine

  Monitor Closely (2)fentanyl transdermal and cyproheptadine both increase sedation. Use Caution/Monitor.
  
  fentanyl transdermal, cyproheptadine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• dantrolene

  Serious - Use Alternative (1)fentanyl transdermal and dantrolene both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• daridorexant

  Monitor Closely (1)fentanyl transdermal and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darunavir

  Monitor Closely (1)darunavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• desflurane

  Serious - Use Alternative (2)fentanyl transdermal, desflurane. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and desflurane both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• desipramine

  Serious - Use Alternative (1)fentanyl transdermal and desipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• deutetrabenazine

  Monitor Closely (1)fentanyl transdermal and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexamethasone

  Monitor Closely (1)dexamethasone will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• dexbrompheniramine

  Monitor Closely (1)fentanyl transdermal and dexbrompheniramine both increase sedation. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (2)fentanyl transdermal, dexchlorpheniramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and dexchlorpheniramine both increase sedation. Use Caution/Monitor.

• diazepam

  Serious - Use Alternative (1)fentanyl transdermal and diazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• diazepam intranasal

  Serious - Use Alternative (1)diazepam intranasal, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• dichlorphenamide

  Monitor Closely (1)dichlorphenamide and fentanyl transdermal both decrease serum potassium. Use Caution/Monitor.

• difelikefalin

  Monitor Closely (1)difelikefalin and fentanyl transdermal both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (1)fentanyl transdermal and difenoxin hcl both increase sedation. Use Caution/Monitor.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• dimenhydrinate

  Monitor Closely (2)fentanyl transdermal, dimenhydrinate. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and dimenhydrinate both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (2)fentanyl transdermal, diphenhydramine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and diphenhydramine both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (1)fentanyl transdermal and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

• doxepin

  Serious - Use Alternative (1)fentanyl transdermal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• doxycycline

  Serious - Use Alternative (1)doxycycline will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• doxylamine

  Monitor Closely (1)fentanyl transdermal and doxylamine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, doxylamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• dronedarone

  Serious - Use Alternative (1)dronedarone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• droperidol

  Serious - Use Alternative (1)fentanyl transdermal and droperidol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• duvelisib

  Monitor Closely (1)duvelisib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

• efavirenz

  Monitor Closely (2)efavirenz will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.
  
  fentanyl transdermal and efavirenz both increase sedation. Use Caution/Monitor.

• elagolix

  Monitor Closely (1)elagolix decreases levels of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

• elranatamab

  Monitor Closely (1)elranatamab will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Elranatamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of elranatamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• eluxadoline

  Monitor Closely (1)eluxadoline increases levels of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Caution when CYP3A substrates that have a narrow therapeutic index are coadministered with eluxadoline.Serious - Use Alternative (1)fentanyl transdermal, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

• encorafenib

  Monitor Closely (1)encorafenib, fentanyl transdermal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

• entacapone

  Monitor Closely (1)fentanyl transdermal and entacapone both increase sedation. Use Caution/Monitor.

• enzalutamide

  Monitor Closely (1)enzalutamide will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• epcoritamab

  Monitor Closely (1)epcoritamab, fentanyl transdermal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Epcoritamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

• erythromycin base

  Serious - Use Alternative (1)erythromycin base will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)erythromycin ethylsuccinate will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• erythromycin lactobionate

  Serious - Use Alternative (1)erythromycin lactobionate will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• erythromycin stearate

  Serious - Use Alternative (1)erythromycin stearate will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• escitalopram

  Serious - Use Alternative (1)fentanyl transdermal, escitalopram. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, fentanyl transdermal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• estazolam

  Serious - Use Alternative (2)fentanyl transdermal, estazolam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and estazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• eszopiclone

  Monitor Closely (1)fentanyl transdermal and eszopiclone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, eszopiclone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• ethacrynic acid

  Monitor Closely (1)fentanyl transdermal decreases effects of ethacrynic acid by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• ethanol

  Monitor Closely (1)fentanyl transdermal and ethanol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, ethanol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• ethosuximide

  Monitor Closely (1)fentanyl transdermal and ethosuximide both increase sedation. Use Caution/Monitor.

• ethotoin

  Monitor Closely (1)fentanyl transdermal and ethotoin both increase sedation. Use Caution/Monitor.

• etomidate

  Serious - Use Alternative (1)fentanyl transdermal, etomidate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• etravirine

  Serious - Use Alternative (1)etravirine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• fedratinib

  Monitor Closely (1)fedratinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

• felbamate

  Monitor Closely (1)fentanyl transdermal and felbamate both increase sedation. Use Caution/Monitor.

• fenfluramine

  Monitor Closely (1)fentanyl transdermal and fenfluramine both increase sedation. Use Caution/Monitor.

• fentanyl

  Serious - Use Alternative (1)fentanyl and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl intranasal

  Serious - Use Alternative (1)fentanyl intranasal and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl iontophoretic transdermal system

  Serious - Use Alternative (1)fentanyl iontophoretic transdermal system and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

• fexofenadine

  Monitor Closely (1)fentanyl transdermal and fexofenadine both increase sedation. Use Caution/Monitor.

• finerenone

  Monitor Closely (1)fentanyl transdermal will increase the level or effect of finerenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor serum potassium during initiation and dosage adjustment of either finererone or weak CYP3A4 inhibitors. Adjust finererone dosage as needed.

• flibanserin

  Monitor Closely (1)fentanyl transdermal and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluconazole

  Serious - Use Alternative (1)fluconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fluoxetine

  Serious - Use Alternative (1)fentanyl transdermal, fluoxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• fluphenazine

  Monitor Closely (1)fentanyl transdermal and fluphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, fluphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• flurazepam

  Serious - Use Alternative (2)fentanyl transdermal, flurazepam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and flurazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fluvoxamine

  Serious - Use Alternative (1)fluvoxamine and fentanyl transdermal both increase serotonin levels. Avoid or Use Alternate Drug.

• fosamprenavir

  Serious - Use Alternative (1)fosamprenavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fosaprepitant

  Serious - Use Alternative (1)fosaprepitant will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• fosphenytoin

  Serious - Use Alternative (1)fosphenytoin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• furosemide

  Monitor Closely (1)fentanyl transdermal decreases effects of furosemide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• gabapentin

  Monitor Closely (1)gabapentin, fentanyl transdermal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.Serious - Use Alternative (1)fentanyl transdermal and gabapentin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• gabapentin enacarbil

  Monitor Closely (1)gabapentin enacarbil, fentanyl transdermal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• ganaxolone

  Monitor Closely (1)fentanyl transdermal and ganaxolone both increase sedation. Use Caution/Monitor.

• glofitamab

  Monitor Closely (1)glofitamab, fentanyl transdermal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Glofitamab causes release of cytokines that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. For certain CYP substrates, minimal changes in their concentration may lead to serious adverse reactions. If needed, modify therapy as recommended in the substrate's prescribing information. .

• grapefruit

  Serious - Use Alternative (1)grapefruit will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• guanfacine

  Monitor Closely (1)fentanyl transdermal and guanfacine both increase sedation. Use Caution/Monitor.

• guselkumab

  Monitor Closely (1)guselkumab, fentanyl transdermal. Other (see comment). Use Caution/Monitor. Comment: Formation of CYP450 enzymes can be altered by increased levels of certain cytokines during chronic inflammation; thus, normalizing the formation of CYP450 enzymes. Upon initiation or discontinuation of guselkumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect.

• haloperidol

  Monitor Closely (1)fentanyl transdermal and haloperidol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)fentanyl transdermal, haloperidol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  haloperidol will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• hydrochlorothiazide

  Monitor Closely (1)fentanyl transdermal decreases effects of hydrochlorothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• hydrocodone

  Serious - Use Alternative (2)hydrocodone, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  fentanyl transdermal and hydrocodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• hydromorphone

  Serious - Use Alternative (2)fentanyl transdermal, hydromorphone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and hydromorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• hydroxyzine

  Monitor Closely (1)fentanyl transdermal, hydroxyzine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.Serious - Use Alternative (1)fentanyl transdermal and hydroxyzine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• iloperidone

  Monitor Closely (1)fentanyl transdermal and iloperidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)iloperidone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• imatinib

  Serious - Use Alternative (1)imatinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• imipramine

  Serious - Use Alternative (1)fentanyl transdermal and imipramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• indapamide

  Monitor Closely (1)fentanyl transdermal decreases effects of indapamide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• indinavir

  Serious - Use Alternative (1)indinavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• isavuconazonium sulfate

  Monitor Closely (2)fentanyl transdermal will increase the level or effect of isavuconazonium sulfate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  isavuconazonium sulfate will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• isocarboxazid

  Contraindicated (1)isocarboxazid increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

• isoflurane

  Serious - Use Alternative (2)fentanyl transdermal, isoflurane. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and isoflurane both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• isoniazid

  Serious - Use Alternative (1)isoniazid will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

• itraconazole

  Serious - Use Alternative (1)itraconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Not recommended during and 2 weeks after itraconazole. If coadministration with fentanyl is necessary, closely monitor for respiratory depression and sedation and consider fentanyl dose adjustments until stable drug effects are achieved.

• ivosidenib

  Serious - Use Alternative (1)ivosidenib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

• ketamine

  Monitor Closely (1)fentanyl transdermal and ketamine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, ketamine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• ketoconazole

  Monitor Closely (1)ketoconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• ketotifen, drug-eluting contact lens

  Monitor Closely (1)fentanyl transdermal and ketotifen, drug-eluting contact lens both increase sedation. Use Caution/Monitor.

• lamotrigine

  Monitor Closely (1)fentanyl transdermal and lamotrigine both increase sedation. Use Caution/Monitor.

• lapatinib

  Serious - Use Alternative (1)lapatinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• larotrectinib

  Monitor Closely (1)larotrectinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved

• lasmiditan

  Monitor Closely (1)lasmiditan, fentanyl transdermal. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

• lemborexant

  Monitor Closely (2)fentanyl transdermal will increase the level or effect of lemborexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Lower nightly dose of lemborexant recommended if coadministered with weak CYP3A4 inhibitors. See drug monograph for specific dosage modification.
  
  lemborexant, fentanyl transdermal. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• lenacapavir

  Monitor Closely (1)lenacapavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Carefully monitor the therapeutic effects and adverse reactions associated with CYP3A-metabolized narcotic analgesics (including potentially fatal respiratory depression) is recommended with coadministration.

• levetiracetam

  Monitor Closely (1)fentanyl transdermal and levetiracetam both increase sedation. Use Caution/Monitor.

• levocetirizine

  Monitor Closely (1)fentanyl transdermal and levocetirizine both increase sedation. Use Caution/Monitor.

• levoketoconazole

  Monitor Closely (1)levoketoconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Monitor for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• levorphanol

  Monitor Closely (1)fentanyl transdermal and levorphanol both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, levorphanol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• lidocaine

  Serious - Use Alternative (1)lidocaine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• linezolid

  Serious - Use Alternative (1)fentanyl transdermal, linezolid. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• lonafarnib

  Serious - Use Alternative (1)fentanyl transdermal will increase the level or effect of lonafarnib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of lonafarnib (a sensitive CYP3A substrate) with weak CYP3A inhibitors is unavoidable, reduce to, or continue lonafarnib at starting dose. Closely monitor for arrhythmias and events (eg, syncope, heart palpitations) since lonafarnib effect on QT interval is unknown.

• loperamide

  Serious - Use Alternative (1)fentanyl transdermal, loperamide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• lopinavir

  Serious - Use Alternative (1)lopinavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• loratadine

  Monitor Closely (1)fentanyl transdermal and loratadine both increase sedation. Use Caution/Monitor.

• lorazepam

  Serious - Use Alternative (1)fentanyl transdermal and lorazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• lorlatinib

  Monitor Closely (1)lorlatinib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• loxapine

  Monitor Closely (1)fentanyl transdermal and loxapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, loxapine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• loxapine inhaled

  Serious - Use Alternative (1)fentanyl transdermal, loxapine inhaled. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• lumacaftor/ivacaftor

  Serious - Use Alternative (1)lumacaftor/ivacaftor will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Lumacaftor is a strong inducer of CYP3A. Avoid coadministration with sensitive CYP3A substrates or CYP3A substrates with a narrow therapeutic index.

• lumateperone

  Monitor Closely (1)fentanyl transdermal and lumateperone both increase sedation. Use Caution/Monitor.

• lurasidone

  Monitor Closely (1)fentanyl transdermal and lurasidone both increase sedation. Use Caution/Monitor.

• maprotiline

  Serious - Use Alternative (1)fentanyl transdermal and maprotiline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• meclizine

  Monitor Closely (1)fentanyl transdermal and meclizine both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (1)fentanyl transdermal and meperidine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, meperidine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• meprobamate

  Monitor Closely (1)fentanyl transdermal and meprobamate both increase sedation. Use Caution/Monitor.

• metaxalone

  Serious - Use Alternative (1)fentanyl transdermal and metaxalone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methadone

  Serious - Use Alternative (2)fentanyl transdermal, methadone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and methadone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methocarbamol

  Serious - Use Alternative (1)fentanyl transdermal and methocarbamol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methohexital

  Serious - Use Alternative (2)fentanyl transdermal, methohexital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and methohexital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methsuximide

  Monitor Closely (1)fentanyl transdermal and methsuximide both increase sedation. Use Caution/Monitor.

• methyclothiazide

  Monitor Closely (1)fentanyl transdermal decreases effects of methyclothiazide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• metoclopramide intranasal

  Serious - Use Alternative (1)fentanyl transdermal, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metolazone

  Monitor Closely (1)fentanyl transdermal decreases effects of metolazone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• metronidazole

  Serious - Use Alternative (1)metronidazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• midazolam

  Serious - Use Alternative (1)fentanyl transdermal and midazolam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• midazolam intranasal

  Monitor Closely (1)midazolam intranasal, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• mifepristone

  Serious - Use Alternative (1)mifepristone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Monitor patients for respiratory depression and sedation at frequent intervals if coadministration of CYP3A4 inhibitors with fentanyl is necessary, and consider fentanyl dose adjustments until stable drug effects achieved

• mirtazapine

  Serious - Use Alternative (1)fentanyl transdermal and mirtazapine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• mitotane

  Monitor Closely (1)mitotane will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• mobocertinib

  Serious - Use Alternative (1)mobocertinib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, increase CYP3A4 substrate dosage in accordance with its prescribing information.

• molindone

  Monitor Closely (1)fentanyl transdermal and molindone both increase sedation. Use Caution/Monitor.

• morphine

  Serious - Use Alternative (2)fentanyl transdermal, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and morphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• nafcillin

  Monitor Closely (1)nafcillin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• nalbuphine

  Serious - Use Alternative (3)fentanyl transdermal, nalbuphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  nalbuphine decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal and nalbuphine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• nefazodone

  Serious - Use Alternative (1)nefazodone will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• nelfinavir

  Serious - Use Alternative (1)nelfinavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• netupitant/palonosetron

  Serious - Use Alternative (1)netupitant/palonosetron will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• nevirapine

  Monitor Closely (1)nevirapine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• nicardipine

  Serious - Use Alternative (1)nicardipine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• nitrous oxide

  Monitor Closely (1)fentanyl transdermal and nitrous oxide both increase sedation. Use Caution/Monitor.

• nortriptyline

  Serious - Use Alternative (1)fentanyl transdermal and nortriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• olanzapine

  Monitor Closely (1)fentanyl transdermal and olanzapine both increase sedation. Use Caution/Monitor.

• oliceridine

  Monitor Closely (1)oliceridine, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.Serious - Use Alternative (1)fentanyl transdermal and oliceridine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• olopatadine intranasal

  Serious - Use Alternative (1)fentanyl transdermal and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• olutasidenib

  Serious - Use Alternative (1)olutasidenib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of olutasidenib (a CYP3A4 inducer) with sensitive CYP3A substrates unless otherwise instructed in substrates prescribing information. If unavoidable, monitor for loss of therapeutic effect of sensitive CYP3A4 substrates.

• opicapone

  Monitor Closely (1)fentanyl transdermal and opicapone both increase sedation. Use Caution/Monitor.

• opium tincture

  Monitor Closely (1)fentanyl transdermal and opium tincture both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, opium tincture. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• orphenadrine

  Serious - Use Alternative (1)fentanyl transdermal and orphenadrine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• oxazepam

  Serious - Use Alternative (1)fentanyl transdermal and oxazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• oxcarbazepine

  Monitor Closely (1)oxcarbazepine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• oxycodone

  Serious - Use Alternative (2)fentanyl transdermal, oxycodone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and oxycodone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• oxymorphone

  Serious - Use Alternative (2)fentanyl transdermal, oxymorphone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and oxymorphone both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• ozanimod

  Serious - Use Alternative (1)ozanimod and fentanyl transdermal both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• paliperidone

  Monitor Closely (1)fentanyl transdermal and paliperidone both increase sedation. Use Caution/Monitor.

• pancuronium

  Serious - Use Alternative (1)fentanyl transdermal, pancuronium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• paroxetine

  Serious - Use Alternative (1)fentanyl transdermal, paroxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• pentazocine

  Serious - Use Alternative (3)fentanyl transdermal, pentazocine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  pentazocine decreases effects of fentanyl transdermal by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Coadministration of mixed agonist/antagonist and partial agonist opioid analgesics may reduce fentanyl's analgesic effect and possibly precipitate withdrawal symptoms.
  
  fentanyl transdermal and pentazocine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• pentobarbital

  Monitor Closely (1)pentobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.Serious - Use Alternative (2)fentanyl transdermal, pentobarbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and pentobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• perampanel

  Monitor Closely (1)fentanyl transdermal and perampanel both increase sedation. Use Caution/Monitor.

• perphenazine

  Monitor Closely (1)fentanyl transdermal and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• phenelzine

  Contraindicated (1)phenelzine increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

• pheniramine

  Serious - Use Alternative (1)fentanyl transdermal and pheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• phenobarbital

  Monitor Closely (1)phenobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.Serious - Use Alternative (1)fentanyl transdermal and phenobarbital both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• phenytoin

  Monitor Closely (1)phenytoin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• pimozide

  Monitor Closely (1)fentanyl transdermal and pimozide both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, pimozide. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• pomalidomide

  Monitor Closely (1)fentanyl transdermal and pomalidomide both increase sedation. Use Caution/Monitor.

• posaconazole

  Serious - Use Alternative (1)posaconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• pregabalin

  Monitor Closely (1)pregabalin, fentanyl transdermal. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.Serious - Use Alternative (1)fentanyl transdermal and pregabalin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• primidone

  Monitor Closely (2)primidone will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.
  
  fentanyl transdermal and primidone both increase sedation. Use Caution/Monitor.

• prochlorperazine

  Serious - Use Alternative (2)fentanyl transdermal, prochlorperazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and prochlorperazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• promethazine

  Monitor Closely (1)fentanyl transdermal, promethazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.Serious - Use Alternative (1)fentanyl transdermal and promethazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• propofol

  Serious - Use Alternative (2)fentanyl transdermal, propofol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and propofol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• protriptyline

  Serious - Use Alternative (1)fentanyl transdermal and protriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• pyrilamine

  Monitor Closely (1)fentanyl transdermal and pyrilamine both increase sedation. Use Caution/Monitor.

• quazepam

  Serious - Use Alternative (2)fentanyl transdermal, quazepam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and quazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• quetiapine

  Serious - Use Alternative (1)fentanyl transdermal and quetiapine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• quinidine

  Serious - Use Alternative (1)quinidine will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• ramelteon

  Monitor Closely (1)fentanyl transdermal and ramelteon both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, ramelteon. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• rasagiline

  Contraindicated (1)rasagiline increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. .

• remifentanil

  Monitor Closely (1)fentanyl transdermal and remifentanil both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• remimazolam

  Monitor Closely (1)remimazolam, fentanyl transdermal. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• reserpine

  Monitor Closely (1)fentanyl transdermal and reserpine both increase sedation. Use Caution/Monitor.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Caution if ribociclib is coadministered with sensitive CYP3A4 substrates that have a narrow therapeutic index. Dose reduction for sensitive CYP3A4 substrates may be needed.

• rifabutin

  Monitor Closely (1)rifabutin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• rifampin

  Monitor Closely (1)rifampin will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• rifapentine

  Monitor Closely (1)rifapentine will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• risperidone

  Monitor Closely (1)fentanyl transdermal and risperidone both increase sedation. Use Caution/Monitor.

• ritonavir

  Serious - Use Alternative (1)ritonavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• rocuronium

  Serious - Use Alternative (1)fentanyl transdermal, rocuronium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• ropeginterferon alfa 2b

  Monitor Closely (1)ropeginterferon alfa 2b will increase the level or effect of fentanyl transdermal by Other (see comment). Use Caution/Monitor. Certain proinflammatory cytokines, including interferons, can suppress CYP450 enzymes resulting in increased exposures of some CYP substrates. Therefore, monitor patients who are receiving concomitant drugs that are CYP450 substrates with a narrow therapeutic index from toxicities to such drugs.

• rucaparib

  Monitor Closely (1)rucaparib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

• safinamide

  Contraindicated (1)fentanyl transdermal, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

• saquinavir

  Serious - Use Alternative (1)saquinavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• schisandra

  Monitor Closely (1)schisandra will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• scopolamine

  Serious - Use Alternative (1)fentanyl transdermal and scopolamine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• secobarbital

  Monitor Closely (1)secobarbital will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects; May also enhance CNS depressant effect of fentanylSerious - Use Alternative (1)fentanyl transdermal, secobarbital. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• selegiline

  Contraindicated (1)selegiline increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. .

• selegiline transdermal

  Contraindicated (1)selegiline transdermal increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics. .

• selinexor

  Serious - Use Alternative (1)selinexor, fentanyl transdermal. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• sertraline

  Serious - Use Alternative (2)fentanyl transdermal, sertraline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
  
  sertraline will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• sevoflurane

  Serious - Use Alternative (2)fentanyl transdermal, sevoflurane. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and sevoflurane both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• sodium oxybate

  Monitor Closely (1)fentanyl transdermal and sodium oxybate both increase sedation. Use Caution/Monitor.

• sotorasib

  Serious - Use Alternative (1)sotorasib will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the CYP3A4 substrate for dosage modifications

• spironolactone

  Monitor Closely (1)fentanyl transdermal decreases effects of spironolactone by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• St John's Wort

  Monitor Closely (1)St John's Wort will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with CYP3A4 inducers could lead to a decrease in fentanyl plasma concentrations, lack of efficacy or, possibly, development of a withdrawal syndrome in a patient who has developed physical dependence to fentanyl. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the fentanyl plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects.

• stiripentol

  Monitor Closely (2)stiripentol, fentanyl transdermal. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
  
  fentanyl transdermal and stiripentol both increase sedation. Use Caution/Monitor.

• succinylcholine

  Serious - Use Alternative (1)fentanyl transdermal, succinylcholine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• sufentanil

  Monitor Closely (1)fentanyl transdermal and sufentanil both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, sufentanil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• sufentanil SL

  Monitor Closely (1)fentanyl transdermal and sufentanil SL both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)sufentanil SL, fentanyl transdermal. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  fentanyl transdermal, sufentanil SL. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• suvorexant

  Monitor Closely (1)fentanyl transdermal and suvorexant both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, suvorexant. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• talquetamab

  Monitor Closely (1)talquetamab will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Talquetamab causes cytokine release syndrome (CRS) that may suppress activity of CYP enzymes, resulting in increased exposure of CYP substrates. This is more likely to occur from initiation of talquetamab step-up dosing up to 14 days after the first treatment dose and during and after CRS.

• tapentadol

  Serious - Use Alternative (2)fentanyl transdermal, tapentadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and tapentadol both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• tasimelteon

  Monitor Closely (1)fentanyl transdermal and tasimelteon both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, tasimelteon. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• tazemetostat

  Monitor Closely (1)tazemetostat will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

• temazepam

  Serious - Use Alternative (2)fentanyl transdermal, temazepam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and temazepam both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• tetrabenazine

  Serious - Use Alternative (1)fentanyl transdermal and tetrabenazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• tetracycline

  Serious - Use Alternative (1)tetracycline will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• thalidomide

  Contraindicated (1)fentanyl transdermal and thalidomide both increase sedation. Contraindicated.

• thioridazine

  Serious - Use Alternative (2)fentanyl transdermal, thioridazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and thioridazine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• thiothixene

  Monitor Closely (1)fentanyl transdermal and thiothixene both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, thiothixene. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• tiagabine

  Monitor Closely (1)fentanyl transdermal and tiagabine both increase sedation. Use Caution/Monitor.

• ticagrelor

  Serious - Use Alternative (1)ticagrelor will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• tipranavir

  Serious - Use Alternative (1)tipranavir will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• tizanidine

  Serious - Use Alternative (1)fentanyl transdermal and tizanidine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• tolcapone

  Monitor Closely (1)fentanyl transdermal and tolcapone both increase sedation. Use Caution/Monitor.

• topiramate

  Monitor Closely (1)fentanyl transdermal and topiramate both increase sedation. Use Caution/Monitor.

• torsemide

  Monitor Closely (1)fentanyl transdermal decreases effects of torsemide by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• tramadol

  Serious - Use Alternative (2)fentanyl transdermal, tramadol. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and tramadol both increase sedation. Avoid or Use Alternate Drug.

• tranylcypromine

  Contraindicated (1)tranylcypromine increases toxicity of fentanyl transdermal by Other (see comment). Contraindicated. Comment: Avoid fentanyl in patients who require concomitant administration MAOIs, or within 14 days of stopping an MAOI. Severe and unpredictable potentiation by MAO inhibitors has been reported with opioid analgesics.

• trazodone

  Monitor Closely (1)fentanyl transdermal and trazodone both increase sedation. Use Caution/Monitor.

• triamterene

  Monitor Closely (1)fentanyl transdermal decreases effects of triamterene by Other (see comment). Modify Therapy/Monitor Closely. Comment: Fentanyl can reduce the efficacy of diuretics by inducing antidiuretic hormone release. Fentanyl may also lead to acute urinary retention by causing bladder sphincter spasm (particularly in men with enlarged prostates).

• triazolam

  Serious - Use Alternative (2)fentanyl transdermal, triazolam. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
  
  fentanyl transdermal and triazolam both increase sedation. Avoid or Use Alternate Drug.

• trifluoperazine

  Monitor Closely (1)fentanyl transdermal and trifluoperazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, trifluoperazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• triprolidine

  Monitor Closely (2)fentanyl transdermal, triprolidine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.
  
  fentanyl transdermal and triprolidine both increase sedation. Use Caution/Monitor.

• tucatinib

  Serious - Use Alternative (1)tucatinib will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

• valerian

  Serious - Use Alternative (1)valerian and fentanyl transdermal both increase sedation. Avoid or Use Alternate Drug.

• valproic acid

  Monitor Closely (1)fentanyl transdermal and valproic acid both increase sedation. Use Caution/Monitor.

• vecuronium

  Serious - Use Alternative (1)fentanyl transdermal, vecuronium. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• verapamil

  Serious - Use Alternative (1)verapamil will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• vigabatrin

  Monitor Closely (1)fentanyl transdermal and vigabatrin both increase sedation. Use Caution/Monitor.

• voriconazole

  Serious - Use Alternative (1)voriconazole will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• vortioxetine

  Serious - Use Alternative (1)fentanyl transdermal, vortioxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

• zaleplon

  Monitor Closely (1)fentanyl transdermal and zaleplon both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, zaleplon. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• ziconotide

  Monitor Closely (1)fentanyl transdermal and ziconotide both increase sedation. Use Caution/Monitor.

• zileuton

  Serious - Use Alternative (1)zileuton will increase the level or effect of fentanyl transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration of CYP3A4 inhibitors with fentanyl is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider fentanyl dose adjustments until stable drug effects are achieved.

• ziprasidone

  Monitor Closely (1)fentanyl transdermal and ziprasidone both increase sedation. Use Caution/Monitor.

• zolpidem

  Monitor Closely (1)fentanyl transdermal and zolpidem both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fentanyl transdermal, zolpidem. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• zonisamide

  Monitor Closely (1)fentanyl transdermal and zonisamide both increase sedation. Use Caution/Monitor.