codeine/chlorpheniramine/phenylephrine (Rx)

Dosing Forms & Strengths

dihydrocodeine/chlorpheniramine/phenylephrine

oral liquid: Schedule III

• (7.5mg/2mg/5mg)/5mL

oral syrup: Schedule V

• (3mg/2mg/7.5mg)/5mL
• (3mg/5mg/20mg)/5mL

Cough and Congestion

5-10 mL PO q4-6hr, up to 40 mL/24 hr

Cough and Congestion

< 2 years: Not recommended

2-6 years: 1.25-2.5 mL PO q4-6hr PRN, up to 10 mL/24 hr

6-12 years: 2.5-5 mL PO q4-6hr, up to 20 mL/24 hr

>12 years: 5-10 mL PO q4-6hr, up to 40 mL/24 hr

Contraindicated (2)

• alvimopan

  alvimopan, codeine. 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.

• iobenguane I 123

  phenylephrine decreases effects of iobenguane I 123 by receptor binding competition. Contraindicated. If clinically appropriate, discontinue drugs that compete for NE receptor sites for at least 5 half-lives; may cause false-negative imaging results.

Serious - Use Alternative (83)

• acrivastine

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

• amisulpride

  amisulpride and codeine both increase sedation. Avoid or Use Alternate Drug.

• amitriptyline

  amitriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• amoxapine

  amoxapine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• apalutamide

  apalutamide will decrease the level or effect of chlorpheniramine 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.

• asenapine

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

• asenapine transdermal

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

• avapritinib

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

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen, codeine. 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.

• bremelanotide

  bremelanotide will decrease the level or effect of codeine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• buprenorphine subdermal implant

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

• brimonidine

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

• buprenorphine

  buprenorphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine buccal

  buprenorphine buccal, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine subdermal implant

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

• buprenorphine transdermal

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

• butorphanol

  butorphanol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• cabergoline

  cabergoline, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• calcium/magnesium/potassium/sodium oxybates

  chlorpheniramine, calcium/magnesium/potassium/sodium oxybates. Either increases effects 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.

• calcium/magnesium/potassium/sodium oxybates

  codeine, calcium/magnesium/potassium/sodium oxybates. Either increases effects 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.

• clomipramine

  clomipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• clonidine

  clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• dacomitinib

  dacomitinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• desflurane

  desflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.
  
  desflurane increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• desipramine

  desipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• diazepam intranasal

  diazepam intranasal, codeine. 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.

• dihydroergotamine

  dihydroergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dihydroergotamine intranasal

  dihydroergotamine intranasal, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• doxapram

  doxapram increases effects of phenylephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive pressor effect.

• doxepin

  doxepin, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• eluxadoline

  chlorpheniramine, 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.
  
  codeine, 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. .

• ergoloid mesylates

  ergoloid mesylates, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• ergotamine

  ergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• ether

  ether increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• etomidate

  etomidate increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• fentanyl

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

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

• fentanyl transdermal

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

• fentanyl transmucosal

  fentanyl transmucosal, 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.

• fexinidazole

  fexinidazole will increase the level or effect of chlorpheniramine 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.

• givosiran

  givosiran will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• hydrocodone

  hydrocodone, codeine. 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.

• idelalisib

  idelalisib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• imipramine

  imipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• isocarboxazid

  isocarboxazid increases effects of chlorpheniramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
  
  isocarboxazid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• isoflurane

  isoflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• linezolid

  linezolid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• lofepramine

  lofepramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• lonafarnib

  lonafarnib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

• maprotiline

  maprotiline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• methoxyflurane

  methoxyflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• methylene blue

  methylene blue and codeine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

• methylergonovine

  methylergonovine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• metoclopramide intranasal

  chlorpheniramine, 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.
  
  codeine, 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.

• nalbuphine

  nalbuphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• nortriptyline

  nortriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• olopatadine intranasal

  chlorpheniramine 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.

• olopatadine intranasal

  codeine 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.

• ozanimod

  ozanimod and codeine 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.

• pentazocine

  pentazocine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• phenelzine

  phenelzine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• prasugrel

  codeine will decrease the level or effect of prasugrel by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of prasugrel and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

• procarbazine

  procarbazine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .

• propofol

  propofol increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• protriptyline

  protriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• rasagiline

  rasagiline increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• selegiline transdermal

  selegiline transdermal increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• selinexor

  selinexor, codeine. 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.

• sevoflurane

  sevoflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.
  
  sevoflurane increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• sodium oxybate

  chlorpheniramine, sodium oxybate. Either increases effects 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.
  
  codeine, sodium oxybate. Either increases effects 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.

• sufentanil SL

  sufentanil SL, codeine. 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.

• tranylcypromine

  tranylcypromine increases effects of chlorpheniramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Tranylcypromine should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• ticagrelor

  codeine will decrease the level or effect of ticagrelor by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of ticagrelor and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

• tramadol

  tramadol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• tranylcypromine

  tranylcypromine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• trazodone

  trazodone, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• trimipramine

  trimipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• tucatinib

  tucatinib will increase the level or effect of chlorpheniramine 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 codeine both increase sedation. Avoid or Use Alternate Drug.

• voxelotor

  voxelotor will increase the level or effect of chlorpheniramine 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.

• yohimbe

  yohimbe, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

Monitor Closely (359)

• abiraterone

  abiraterone increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

• acrivastine

  acrivastine and chlorpheniramine both increase sedation. Use Caution/Monitor.

• albuterol

  albuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  albuterol and phenylephrine both decrease sedation. Use Caution/Monitor.

• alfentanil

  alfentanil increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and alfentanil both increase sedation. Use Caution/Monitor.
  
  alfentanil and codeine both increase sedation. Use Caution/Monitor.

• alprazolam

  alprazolam and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and alprazolam both increase sedation. Use Caution/Monitor.
  
  alprazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• amifampridine

  chlorpheniramine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amitriptyline

  amitriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• amiodarone

  amiodarone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• amisulpride

  amisulpride and chlorpheniramine both increase sedation. Use Caution/Monitor.

• amitriptyline

  chlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  codeine and amitriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

  amobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and amobarbital both increase sedation. Use Caution/Monitor.

• amoxapine

  amoxapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and amoxapine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and amoxapine both increase sedation. Use Caution/Monitor.

• apomorphine

  codeine and apomorphine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and apomorphine both increase sedation. Use Caution/Monitor.

• arformoterol

  arformoterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  arformoterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• arformoterol

  chlorpheniramine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• aripiprazole

  aripiprazole increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and aripiprazole both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and aripiprazole both increase sedation. Use Caution/Monitor.

• armodafinil

  codeine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  armodafinil and phenylephrine both decrease sedation. Use Caution/Monitor.

• artemether/lumefantrine

  artemether/lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• atomoxetine

  atomoxetine, phenylephrine. Other (see comment). Use Caution/Monitor. Comment: Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine.

• asenapine

  asenapine and chlorpheniramine both increase sedation. Use Caution/Monitor.

• asenapine transdermal

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

• avapritinib

  avapritinib and chlorpheniramine both increase sedation. Use Caution/Monitor.

• azelastine

  azelastine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  azelastine and codeine both increase sedation. Use Caution/Monitor.
  
  azelastine and chlorpheniramine both increase sedation. Use Caution/Monitor.

• baclofen

  chlorpheniramine and baclofen both increase sedation. Use Caution/Monitor.
  
  baclofen and codeine both increase sedation. Use Caution/Monitor.

• belladonna and opium

  belladonna and opium increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• belladonna and opium

  codeine and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and belladonna and opium both increase sedation. Use Caution/Monitor.

• belzutifan

  belzutifan will decrease the level or effect of chlorpheniramine 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.

• benperidol

  codeine and benperidol both increase sedation. Use Caution/Monitor.
  
  benperidol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benperidol

  chlorpheniramine and benperidol both increase sedation. Use Caution/Monitor.

• benzphetamine

  benzphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  benzphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• benzphetamine

  chlorpheniramine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• brexanolone

  brexanolone, codeine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
  
  brexanolone, chlorpheniramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  brexpiprazole and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  brexpiprazole and codeine both increase sedation. Use Caution/Monitor.

• brimonidine

  brimonidine and chlorpheniramine both increase sedation. Use Caution/Monitor.

• brivaracetam

  brivaracetam and codeine both increase sedation. Use Caution/Monitor.

• brivaracetam

  brivaracetam and chlorpheniramine both increase sedation. Use Caution/Monitor.

• bromocriptine

  bromocriptine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Hypertension, V tach.

• brompheniramine

  brompheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  brompheniramine and codeine both increase sedation. Use Caution/Monitor.
  
  brompheniramine and chlorpheniramine both increase sedation. Use Caution/Monitor.

• buprenorphine

  buprenorphine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and buprenorphine both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  buprenorphine buccal increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• buprenorphine buccal

  chlorpheniramine and buprenorphine buccal both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal and codeine both increase sedation. Use Caution/Monitor.

• buprenorphine, long-acting injection

  codeine 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.

• butabarbital

  butabarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and butabarbital both increase sedation. Use Caution/Monitor.

• bupropion

  bupropion will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents the conversion of codeine to its active metabolite morphine.

• butalbital

  butalbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• butabarbital

  butabarbital and codeine both increase sedation. Use Caution/Monitor.

• butalbital

  chlorpheniramine and butalbital both increase sedation. Use Caution/Monitor.
  
  butalbital and codeine both increase sedation. Use Caution/Monitor.

• butorphanol

  butorphanol and codeine both increase sedation. Use Caution/Monitor.
  
  butorphanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and butorphanol both increase sedation. Use Caution/Monitor.

• caffeine

  chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.

• carbinoxamine

  carbinoxamine and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  carbinoxamine and codeine both increase sedation. Use Caution/Monitor.
  
  carbinoxamine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carisoprodol

  carisoprodol and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and carisoprodol both increase sedation. Use Caution/Monitor.

• chloral hydrate

  chloral hydrate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• celecoxib

  celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cenobamate

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

• cenobamate

  cenobamate, codeine. Either increases effects of the other by sedation. Use Caution/Monitor.

• chloral hydrate

  chloral hydrate and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and chloral hydrate both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  chlorpheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chloroquine

  chloroquine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• chlorpheniramine

  chlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpromazine

  chlorpheniramine and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  chlorpromazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpheniramine

  chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.

• cinnarizine

  cinnarizine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpromazine

  codeine and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine

• chlorzoxazone

  chlorzoxazone and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cimetidine

  cimetidine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cinnarizine

  chlorpheniramine and cinnarizine both increase sedation. Use Caution/Monitor.

• cinacalcet

  cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cinnarizine

  cinnarizine and codeine both increase sedation. Use Caution/Monitor.

• clemastine

  clemastine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and clemastine both increase sedation. Use Caution/Monitor.
  
  clemastine and codeine both increase sedation. Use Caution/Monitor.

• clobazam

  chlorpheniramine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  codeine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  clobazam decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• clomipramine

  clomipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clomipramine

  codeine and clomipramine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and clomipramine both increase sedation. Use Caution/Monitor.
  
  clomipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• clonazepam

  clonazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and clonazepam both increase sedation. Use Caution/Monitor.
  
  clonazepam and codeine both increase sedation. Use Caution/Monitor.

• clorazepate

  clorazepate and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and clorazepate both increase sedation. Use Caution/Monitor.
  
  clorazepate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clozapine

  codeine and clozapine both increase sedation. Use Caution/Monitor.
  
  clozapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and clozapine both increase sedation. Use Caution/Monitor.
  
  clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cocaine topical

  cocaine topical decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• codeine

  codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• codeine

  chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.

• crofelemer

  crofelemer increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclizine

  cyclizine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and cyclizine both increase sedation. Use Caution/Monitor.
  
  cyclizine and codeine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  chlorpheniramine and cyclobenzaprine both increase sedation. Use Caution/Monitor.
  
  cyclobenzaprine and codeine both increase sedation. Use Caution/Monitor.

• cyproheptadine

  cyproheptadine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• cyproheptadine

  cyproheptadine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and cyproheptadine both increase sedation. Use Caution/Monitor.

• dabrafenib

  dabrafenib will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dantrolene

  dantrolene and codeine both increase sedation. Use Caution/Monitor.

• dantrolene

  chlorpheniramine and dantrolene both increase sedation. Use Caution/Monitor.

• daridorexant

  chlorpheniramine 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.
  
  codeine 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.

• darifenacin

  darifenacin decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• desflurane

  desflurane and chlorpheniramine both increase sedation. Use Caution/Monitor.

• desflurane

  desflurane and codeine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.

• desipramine

  chlorpheniramine and desipramine both increase sedation. Use Caution/Monitor.
  
  codeine and desipramine both increase sedation. Use Caution/Monitor.
  
  desipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  desipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• desvenlafaxine

  desvenlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

• dexchlorpheniramine

  dexchlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• deutetrabenazine

  chlorpheniramine and deutetrabenazine both increase sedation. Use Caution/Monitor.

• deutetrabenazine

  codeine and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexchlorpheniramine

  chlorpheniramine and dexchlorpheniramine both increase sedation. Use Caution/Monitor.
  
  dexchlorpheniramine and codeine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  chlorpheniramine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexfenfluramine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  dexfenfluramine and phenylephrine both decrease sedation. Use Caution/Monitor.

• dexmedetomidine

  dexmedetomidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and dexmedetomidine both increase sedation. Use Caution/Monitor.
  
  dexmedetomidine and codeine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  dexmethylphenidate and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexmethylphenidate and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  dextroamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dextroamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dextromoramide

  chlorpheniramine and dextromoramide both increase sedation. Use Caution/Monitor.
  
  codeine and dextromoramide both increase sedation. Use Caution/Monitor.
  
  dextromoramide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diamorphine

  chlorpheniramine and diamorphine both increase sedation. Use Caution/Monitor.
  
  codeine and diamorphine both increase sedation. Use Caution/Monitor.
  
  diamorphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diazepam

  chlorpheniramine and diazepam both increase sedation. Use Caution/Monitor.
  
  diazepam and codeine both increase sedation. Use Caution/Monitor.

• diethylpropion

  diethylpropion and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  diethylpropion and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• diazepam intranasal

  diazepam intranasal, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• diethylpropion

  codeine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diethylpropion

  chlorpheniramine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  difelikefalin and codeine both increase sedation. Use Caution/Monitor.
  
  difelikefalin and chlorpheniramine both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  difenoxin hcl increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and difenoxin hcl both increase sedation. Use Caution/Monitor.
  
  codeine and difenoxin hcl both increase sedation. Use Caution/Monitor.

• dimenhydrinate

  dimenhydrinate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and dimenhydrinate both increase sedation. Use Caution/Monitor.
  
  dimenhydrinate and codeine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  diphenhydramine and codeine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and diphenhydramine both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  diphenoxylate hcl increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipipanone

  chlorpheniramine and dipipanone both increase sedation. Use Caution/Monitor.
  
  codeine and dipipanone both increase sedation. Use Caution/Monitor.
  
  dipipanone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dobutamine

  codeine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dobutamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dobutamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• donepezil transdermal

  donepezil transdermal, chlorpheniramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

• dopamine

  dopamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dopamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dopamine

  codeine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopamine

  chlorpheniramine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopexamine

  dopexamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dopexamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  chlorpheniramine and dosulepin both increase sedation. Use Caution/Monitor.
  
  codeine and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  doxepin increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• doxepin

  codeine and doxepin both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and doxepin both increase sedation. Use Caution/Monitor.

• doxylamine

  doxylamine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• dronedarone

  dronedarone decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• droperidol

  droperidol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and droperidol both increase sedation. Use Caution/Monitor.

• droperidol

  codeine and droperidol both increase sedation. Use Caution/Monitor.

• droxidopa

  phenylephrine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

• duloxetine

  duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• efavirenz

  efavirenz will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elagolix

  elagolix will decrease the level or effect of chlorpheniramine 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.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• ephedrine

  ephedrine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.
  
  ephedrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  ephedrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  epinephrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  epinephrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine inhaled

  phenylephrine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  chlorpheniramine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine racemic

  epinephrine racemic and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  epinephrine racemic and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• esketamine intranasal

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

• estazolam

  estazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  estazolam and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and estazolam both increase sedation. Use Caution/Monitor.

• ethanol

  ethanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and ethanol both increase sedation. Use Caution/Monitor.
  
  codeine and ethanol both increase sedation. Use Caution/Monitor.

• etomidate

  etomidate and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  etomidate and codeine both increase sedation. Use Caution/Monitor.

• fenfluramine

  fenfluramine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  fenfluramine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• fedratinib

  fedratinib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
  
  fedratinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• fenfluramine

  chlorpheniramine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fentanyl

  fentanyl, 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.

• flibanserin

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

• fentanyl intranasal

  fentanyl intranasal, 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.

• fentanyl transdermal

  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.

• fentanyl transmucosal

  fentanyl transmucosal, 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.

• flibanserin

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

• fluoxetine

  fluoxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine

• fluphenazine

  fluphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and fluphenazine both increase sedation. Use Caution/Monitor.
  
  fluphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  codeine and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  chlorpheniramine and flurazepam both increase sedation. Use Caution/Monitor.
  
  flurazepam and codeine both increase sedation. Use Caution/Monitor.
  
  flurazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• formoterol

  chlorpheniramine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  formoterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  formoterol and phenylephrine both decrease sedation. Use Caution/Monitor.

• fosphenytoin

  fosphenytoin will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• haloperidol

  haloperidol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• gabapentin

  gabapentin, codeine. 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

  gabapentin, chlorpheniramine. 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, codeine. 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, chlorpheniramine. 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

  codeine and ganaxolone both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and ganaxolone both increase sedation. Use Caution/Monitor.

• glycopyrronium tosylate topical

  glycopyrronium tosylate topical, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

• haloperidol

  haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  codeine and haloperidol both increase sedation. Use Caution/Monitor.

• gotu kola

  gotu kola increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• haloperidol

  chlorpheniramine and haloperidol both increase sedation. Use Caution/Monitor.

• hawthorn

  hawthorn increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hops

  hops increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hyaluronidase

  chlorpheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

• hydralazine

  hydralazine, phenylephrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

• hydromorphone

  chlorpheniramine and hydromorphone both increase sedation. Use Caution/Monitor.
  
  hydromorphone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and hydromorphone both increase sedation. Use Caution/Monitor.

• hydroxyzine

  chlorpheniramine and hydroxyzine both increase sedation. Use Caution/Monitor.
  
  hydroxyzine and codeine both increase sedation. Use Caution/Monitor.
  
  hydroxyzine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• iloperidone

  codeine and iloperidone both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and iloperidone both increase sedation. Use Caution/Monitor.
  
  iloperidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  iloperidone increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• imipramine

  codeine and imipramine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and imipramine both increase sedation. Use Caution/Monitor.
  
  imipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  imipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• indacaterol, inhaled

  phenylephrine increases effects of indacaterol, inhaled by Other (see comment). Use Caution/Monitor. Comment: If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of indacaterol may be potentiated.

• isoniazid

  isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• insulin degludec

  phenylephrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• insulin degludec/insulin aspart

  phenylephrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• insulin inhaled

  phenylephrine decreases effects of insulin inhaled by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• isoproterenol

  isoproterenol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  isoproterenol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• isoproterenol

  codeine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ketotifen, ophthalmic

  ketotifen, ophthalmic increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• istradefylline

  istradefylline will increase the level or effect of chlorpheniramine 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.

• kava

  kava increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  ketamine and codeine both increase sedation. Use Caution/Monitor.
  
  ketamine and chlorpheniramine both increase sedation. Use Caution/Monitor.

• ketoconazole

  ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• ketotifen, ophthalmic

  chlorpheniramine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• ketotifen, ophthalmic

  codeine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• lasmiditan

  lasmiditan, chlorpheniramine. 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.
  
  lasmiditan, codeine. 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

  lemborexant, codeine. 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.
  
  lemborexant, chlorpheniramine. 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 chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• letermovir

  letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• letermovir

  letermovir increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  levalbuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  levalbuterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levoketoconazole

  levoketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• levorphanol

  levorphanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levorphanol

  chlorpheniramine and levorphanol both increase sedation. Use Caution/Monitor.

• levorphanol

  codeine and levorphanol both increase sedation. Use Caution/Monitor.

• lisdexamfetamine

  lisdexamfetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  lisdexamfetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lofepramine

  chlorpheniramine and lofepramine both increase sedation. Use Caution/Monitor.
  
  codeine and lofepramine both increase sedation. Use Caution/Monitor.
  
  lofepramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lofexidine

  codeine and lofexidine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and lofexidine both increase sedation. Use Caution/Monitor.
  
  lofexidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lopinavir

  lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• loprazolam

  loprazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loprazolam

  chlorpheniramine and loprazolam both increase sedation. Use Caution/Monitor.

• loprazolam

  loprazolam and codeine both increase sedation. Use Caution/Monitor.

• lorazepam

  lorazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and lorazepam both increase sedation. Use Caution/Monitor.
  
  lorazepam and codeine both increase sedation. Use Caution/Monitor.

• lorcaserin

  lorcaserin will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• lormetazepam

  lormetazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lormetazepam

  chlorpheniramine and lormetazepam both increase sedation. Use Caution/Monitor.

• lormetazepam

  lormetazepam and codeine both increase sedation. Use Caution/Monitor.

• loxapine

  chlorpheniramine and loxapine both increase sedation. Use Caution/Monitor.
  
  codeine and loxapine both increase sedation. Use Caution/Monitor.
  
  loxapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine inhaled

  loxapine inhaled increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and loxapine inhaled both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lumefantrine

  lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• maprotiline

  maprotiline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lurasidone

  lurasidone, chlorpheniramine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• lurasidone

  lurasidone, codeine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• maprotiline

  chlorpheniramine and maprotiline both increase sedation. Use Caution/Monitor.
  
  codeine and maprotiline both increase sedation. Use Caution/Monitor.

• marijuana

  chlorpheniramine and marijuana both increase sedation. Use Caution/Monitor.
  
  marijuana increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and marijuana both increase sedation. Use Caution/Monitor.

• melatonin

  melatonin increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and melatonin both increase sedation. Use Caution/Monitor.
  
  codeine and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  codeine and meperidine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and meperidine both increase sedation. Use Caution/Monitor.
  
  meperidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• meprobamate

  meprobamate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and meprobamate both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and meprobamate both increase sedation. Use Caution/Monitor.

• metaproterenol

  metaproterenol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  metaproterenol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  chlorpheniramine and metaxalone both increase sedation. Use Caution/Monitor.
  
  metaxalone and codeine both increase sedation. Use Caution/Monitor.

• methadone

  methadone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methadone

  chlorpheniramine and methadone both increase sedation. Use Caution/Monitor.
  
  codeine and methadone both increase sedation. Use Caution/Monitor.

• methamphetamine

  methamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  methamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• methocarbamol

  chlorpheniramine and methocarbamol both increase sedation. Use Caution/Monitor.
  
  methocarbamol and codeine both increase sedation. Use Caution/Monitor.

• methyldopa

  methyldopa increases effects of phenylephrine by unknown mechanism. Use Caution/Monitor.

• methylenedioxymethamphetamine

  chlorpheniramine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  methylenedioxymethamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  methylenedioxymethamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• midazolam

  midazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and midazolam both increase sedation. Use Caution/Monitor.
  
  midazolam and codeine both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  midazolam intranasal, codeine. Either increases effects 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.
  
  midazolam intranasal, chlorpheniramine. Either increases effects 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.

• midodrine

  midodrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  midodrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• midodrine

  codeine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mirabegron

  mirabegron will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  chlorpheniramine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  mirtazapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mirtazapine

  codeine and mirtazapine both increase sedation. Use Caution/Monitor.

• modafinil

  modafinil and phenylephrine both decrease sedation. Use Caution/Monitor.

• mitotane

  mitotane decreases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• modafinil

  codeine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• morphine

  chlorpheniramine and morphine both increase sedation. Use Caution/Monitor.
  
  codeine and morphine both increase sedation. Use Caution/Monitor.
  
  morphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• motherwort

  chlorpheniramine and motherwort both increase sedation. Use Caution/Monitor.
  
  codeine and motherwort both increase sedation. Use Caution/Monitor.
  
  motherwort increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moxonidine

  codeine and moxonidine both increase sedation. Use Caution/Monitor.
  
  moxonidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  codeine and nabilone both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and nabilone both increase sedation. Use Caution/Monitor.
  
  nabilone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nadolol

  nadolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• nalbuphine

  codeine and nalbuphine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and nalbuphine both increase sedation. Use Caution/Monitor.

• nalbuphine

  nalbuphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• norepinephrine

  norepinephrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  norepinephrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nortriptyline

  codeine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• olanzapine

  codeine and olanzapine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and olanzapine both increase sedation. Use Caution/Monitor.
  
  olanzapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oliceridine

  oliceridine, codeine. 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.

• olodaterol inhaled

  phenylephrine and olodaterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Caution with coadministration of adrenergic drugs by any route because of additive sympathetic effects

• opium tincture

  chlorpheniramine and opium tincture both increase sedation. Use Caution/Monitor.
  
  opium tincture increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• opium tincture

  codeine and opium tincture both increase sedation. Use Caution/Monitor.

• oxazepam

  oxazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• orphenadrine

  orphenadrine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and orphenadrine both increase sedation. Use Caution/Monitor.

• oxazepam

  oxazepam and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and oxazepam both increase sedation. Use Caution/Monitor.

• oxycodone

  oxycodone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and oxycodone both increase sedation. Use Caution/Monitor.
  
  codeine and oxycodone both increase sedation. Use Caution/Monitor.

• oxymetazoline topical

  oxymetazoline topical and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• oxymorphone

  codeine and oxymorphone both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and oxymorphone both increase sedation. Use Caution/Monitor.

• oxymorphone

  oxymorphone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxytocin

  oxytocin increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor.

• paliperidone

  chlorpheniramine and paliperidone both increase sedation. Use Caution/Monitor.
  
  paliperidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and paliperidone both increase sedation. Use Caution/Monitor.

• papaveretum

  codeine and papaveretum both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and papaveretum both increase sedation. Use Caution/Monitor.
  
  papaveretum increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• papaverine

  chlorpheniramine and papaverine both increase sedation. Use Caution/Monitor.
  
  codeine and papaverine both increase sedation. Use Caution/Monitor.

• pentazocine

  pentazocine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• paroxetine

  paroxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• passion flower

  passion flower increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• peginterferon alfa 2b

  peginterferon alfa 2b, codeine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

• pegvisomant

  codeine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

• pentazocine

  chlorpheniramine and pentazocine both increase sedation. Use Caution/Monitor.
  
  codeine and pentazocine both increase sedation. Use Caution/Monitor.

• pentobarbital

  pentobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and pentobarbital both increase sedation. Use Caution/Monitor.
  
  pentobarbital and codeine both increase sedation. Use Caution/Monitor.

• perampanel

  perampanel and codeine both increase sedation. Use Caution/Monitor.

• perphenazine

  perphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• perphenazine

  chlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• perphenazine

  codeine and perphenazine both increase sedation. Use Caution/Monitor.

• phendimetrazine

  codeine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phendimetrazine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phendimetrazine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• phenelzine

  phenelzine increases effects of chlorpheniramine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .

• phenobarbital

  phenobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenobarbital

  phenobarbital and codeine both increase sedation. Use Caution/Monitor.

• phenobarbital

  chlorpheniramine and phenobarbital both increase sedation. Use Caution/Monitor.

• phentermine

  phentermine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phentermine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine

  chlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pholcodine

  pholcodine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine PO

  codeine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
  
  chlorpheniramine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• pholcodine

  chlorpheniramine and pholcodine both increase sedation. Use Caution/Monitor.
  
  codeine and pholcodine both increase sedation. Use Caution/Monitor.

• pimozide

  codeine and pimozide both increase sedation. Use Caution/Monitor.
  
  pimozide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and pimozide both increase sedation. Use Caution/Monitor.

• pindolol

  pindolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• pirbuterol

  codeine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pirbuterol

  pirbuterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  pirbuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• pregabalin

  pregabalin, codeine. 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.
  
  pregabalin, chlorpheniramine. 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 increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and primidone both increase sedation. Use Caution/Monitor.
  
  primidone and codeine both increase sedation. Use Caution/Monitor.

• prochlorperazine

  chlorpheniramine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  codeine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  prochlorperazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  prochlorperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• promazine

  promazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• promethazine

  chlorpheniramine and promethazine both increase sedation. Use Caution/Monitor.
  
  promethazine and codeine both increase sedation. Use Caution/Monitor.

• promethazine

  promethazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  promethazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• propofol

  propofol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  propofol and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  propofol and codeine both increase sedation. Use Caution/Monitor.

• propranolol

  propranolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• propylhexedrine

  codeine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• propylhexedrine

  phenylephrine and propylhexedrine both decrease sedation. Use Caution/Monitor.
  
  phenylephrine and propylhexedrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• protriptyline

  chlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.
  
  codeine and protriptyline both increase sedation. Use Caution/Monitor.
  
  protriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pseudoephedrine

  phenylephrine and pseudoephedrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• quazepam

  chlorpheniramine and quazepam both increase sedation. Use Caution/Monitor.
  
  quazepam and codeine both increase sedation. Use Caution/Monitor.

• quazepam

  quazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quetiapine

  quetiapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and quetiapine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and quetiapine both increase sedation. Use Caution/Monitor.

• quinidine

  quinidine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• rasagiline

  rasagiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• ramelteon

  chlorpheniramine and ramelteon both increase sedation. Use Caution/Monitor.

• ramelteon

  codeine and ramelteon both increase sedation. Use Caution/Monitor.

• remimazolam

  remimazolam, codeine. 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.

• ribociclib

  ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• risperidone

  codeine and risperidone both increase sedation. Use Caution/Monitor.
  
  risperidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and risperidone both increase sedation. Use Caution/Monitor.

• ritonavir

  ritonavir will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• safinamide

  phenylephrine and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

• rucaparib

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

• rolapitant

  rolapitant will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• salmeterol

  chlorpheniramine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  salmeterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  salmeterol and phenylephrine both decrease sedation. Use Caution/Monitor.

• scullcap

  codeine and scullcap both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and scullcap both increase sedation. Use Caution/Monitor.
  
  scullcap increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• secobarbital

  secobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  secobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and secobarbital both increase sedation. Use Caution/Monitor.

• selegiline

  selegiline increases toxicity of codeine by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.
  
  selegiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• serdexmethylphenidate/dexmethylphenidate

  serdexmethylphenidate/dexmethylphenidate and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  serdexmethylphenidate/dexmethylphenidate and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• sertraline

  sertraline decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• sevoflurane

  sevoflurane and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  sevoflurane and codeine both increase sedation. Use Caution/Monitor.

• shepherd's purse

  chlorpheniramine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  codeine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  shepherd's purse increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• solriamfetol

  phenylephrine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• stiripentol

  stiripentol, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
  
  stiripentol, chlorpheniramine. 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.

• sufentanil

  sufentanil increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and sufentanil both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and sufentanil both increase sedation. Use Caution/Monitor.

• suvorexant

  suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tapentadol

  tapentadol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tapentadol

  chlorpheniramine and tapentadol both increase sedation. Use Caution/Monitor.

• tapentadol

  codeine and tapentadol both increase sedation. Use Caution/Monitor.

• tazemetostat

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

• tecovirimat

  tecovirimat will decrease the level or effect of chlorpheniramine 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

  temazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and temazepam both increase sedation. Use Caution/Monitor.
  
  temazepam and codeine both increase sedation. Use Caution/Monitor.

• terbinafine

  terbinafine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• terbutaline

  terbutaline and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  terbutaline and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• terbutaline

  chlorpheniramine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• terbutaline

  codeine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• thioridazine

  thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  codeine and thioridazine both increase sedation. Use Caution/Monitor.
  
  thioridazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  thioridazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  chlorpheniramine and thioridazine both increase sedation. Use Caution/Monitor.

• thiothixene

  chlorpheniramine and thiothixene both increase sedation. Use Caution/Monitor.
  
  codeine and thiothixene both increase sedation. Use Caution/Monitor.
  
  thiothixene increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ticlopidine

  ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• timolol

  timolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• topiramate

  topiramate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  chlorpheniramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• topiramate

  codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

  tramadol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tramadol

  chlorpheniramine and tramadol both increase sedation. Use Caution/Monitor.
  
  codeine and tramadol both increase sedation. Use Caution/Monitor.

• tranylcypromine

  tranylcypromine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• trazodone

  chlorpheniramine and trazodone both increase sedation. Use Caution/Monitor.
  
  trazodone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trazodone

  codeine and trazodone both increase sedation. Use Caution/Monitor.

• triazolam

  triazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• triazolam

  chlorpheniramine and triazolam both increase sedation. Use Caution/Monitor.
  
  triazolam and codeine both increase sedation. Use Caution/Monitor.

• triclofos

  triclofos and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and triclofos both increase sedation. Use Caution/Monitor.
  
  triclofos increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trifluoperazine

  chlorpheniramine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  codeine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  trifluoperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• trimipramine

  codeine and trimipramine both increase sedation. Use Caution/Monitor.
  
  trimipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and trimipramine both increase sedation. Use Caution/Monitor.

• triprolidine

  triprolidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and triprolidine both increase sedation. Use Caution/Monitor.
  
  triprolidine and codeine both increase sedation. Use Caution/Monitor.

• valerian

  valerian increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• xylometazoline

  phenylephrine and xylometazoline both decrease sedation. Use Caution/Monitor.
  
  phenylephrine and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• venlafaxine

  venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• xylometazoline

  chlorpheniramine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• yohimbine

  yohimbine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  phenylephrine and yohimbine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ziconotide

  codeine and ziconotide both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and ziconotide both increase sedation. Use Caution/Monitor.
  
  ziconotide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ziprasidone

  codeine and ziprasidone both increase sedation. Use Caution/Monitor.
  
  ziprasidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and ziprasidone both increase sedation. Use Caution/Monitor.

• zotepine

  codeine and zotepine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and zotepine both increase sedation. Use Caution/Monitor.

Minor (36)

• acetazolamide

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

• alfuzosin

  alfuzosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• anastrozole

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

• asenapine

  asenapine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.
  
  asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ashwagandha

  ashwagandha increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• desmopressin

  desmopressin increases effects of phenylephrine by pharmacodynamic synergism. Minor/Significance Unknown.

• brimonidine

  brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
  
  brimonidine increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• cyclophosphamide

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

• dextroamphetamine

  dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.

• doxazosin

  doxazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• eucalyptus

  eucalyptus increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  codeine and eucalyptus both increase sedation. Minor/Significance Unknown.
  
  chlorpheniramine and eucalyptus both increase sedation. Minor/Significance Unknown.

• fluoxetine

  fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• moxisylyte

  moxisylyte, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• larotrectinib

  larotrectinib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• imatinib

  imatinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  imatinib decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• levoketoconazole

  levoketoconazole will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lidocaine

  lidocaine increases toxicity of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

• maraviroc

  maraviroc will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  marijuana will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• nettle

  nettle increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nilotinib

  nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• parecoxib

  parecoxib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• perphenazine

  perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• phenoxybenzamine

  phenoxybenzamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• phentolamine

  phentolamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• prazosin

  prazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• propafenone

  propafenone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  propafenone decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• quinacrine

  quinacrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  quinacrine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• ranolazine

  ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ribociclib

  ribociclib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sage

  sage increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  codeine and sage both increase sedation. Minor/Significance Unknown.
  
  chlorpheniramine and sage both increase sedation. Minor/Significance Unknown.

• Siberian ginseng

  Siberian ginseng increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• silodosin

  silodosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• sertraline

  sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• terazosin

  terazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• thioridazine

  thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• abiraterone

  Monitor Closely (1)abiraterone increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

• acetazolamide

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

• acrivastine

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

• albuterol

  Monitor Closely (4)chlorpheniramine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  albuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  albuterol and phenylephrine both decrease sedation. Use Caution/Monitor.

• alfentanil

  Monitor Closely (3)alfentanil increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and alfentanil both increase sedation. Use Caution/Monitor.
  
  alfentanil and codeine both increase sedation. Use Caution/Monitor.

• alfuzosin

  Minor (1)alfuzosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• alprazolam

  Monitor Closely (3)alprazolam and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and alprazolam both increase sedation. Use Caution/Monitor.
  
  alprazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alvimopan

  Contraindicated (1)alvimopan, codeine. 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.

• amifampridine

  Monitor Closely (1)chlorpheniramine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• amisulpride

  Monitor Closely (1)amisulpride and chlorpheniramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amisulpride and codeine both increase sedation. Avoid or Use Alternate Drug.

• amitriptyline

  Monitor Closely (3)amitriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  codeine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• amobarbital

  Monitor Closely (4)amobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and amobarbital both increase sedation. Use Caution/Monitor.

• amoxapine

  Monitor Closely (3)amoxapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and amoxapine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and amoxapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amoxapine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• anastrozole

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

• apalutamide

  Serious - Use Alternative (1)apalutamide will decrease the level or effect of chlorpheniramine 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.

• apomorphine

  Monitor Closely (2)codeine and apomorphine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and apomorphine both increase sedation. Use Caution/Monitor.

• arformoterol

  Monitor Closely (4)chlorpheniramine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  arformoterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  arformoterol and phenylephrine both decrease sedation. Use Caution/Monitor.

• aripiprazole

  Monitor Closely (3)aripiprazole increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and aripiprazole both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and aripiprazole both increase sedation. Use Caution/Monitor.

• armodafinil

  Monitor Closely (3)codeine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  armodafinil and phenylephrine both decrease sedation. Use Caution/Monitor.

• artemether/lumefantrine

  Monitor Closely (1)artemether/lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• asenapine

  Monitor Closely (1)asenapine and chlorpheniramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)asenapine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequateMinor (2)asenapine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.
  
  asenapine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• asenapine transdermal

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

• ashwagandha

  Minor (1)ashwagandha increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• atomoxetine

  Monitor Closely (1)atomoxetine, phenylephrine. Other (see comment). Use Caution/Monitor. Comment: Due to the potential for increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as phenylephrine.

• avapritinib

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

• azelastine

  Monitor Closely (3)azelastine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  azelastine and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  azelastine and codeine both increase sedation. Use Caution/Monitor.

• baclofen

  Monitor Closely (2)chlorpheniramine and baclofen both increase sedation. Use Caution/Monitor.
  
  baclofen and codeine both increase sedation. Use Caution/Monitor.

• belladonna and opium

  Monitor Closely (3)codeine and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and belladonna and opium both increase sedation. Use Caution/Monitor.
  
  belladonna and opium increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• belzutifan

  Monitor Closely (1)belzutifan will decrease the level or effect of chlorpheniramine 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.

• benperidol

  Monitor Closely (3)codeine and benperidol both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and benperidol both increase sedation. Use Caution/Monitor.
  
  benperidol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Serious - Use Alternative (3)benzhydrocodone/acetaminophen and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen, codeine. 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.

• benzphetamine

  Monitor Closely (4)chlorpheniramine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  benzphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  benzphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• bremelanotide

  Serious - Use Alternative (1)bremelanotide will decrease the level or effect of codeine by Other (see comment). Avoid or Use Alternate Drug. Bremelanotide may slow gastric emptying and potentially reduces the rate and extent of absorption of concomitantly administered oral medications. Avoid use when taking any oral drug that is dependent on threshold concentrations for efficacy. Interactions listed are representative examples and do not include all possible clinical examples.

• brexanolone

  Monitor Closely (2)brexanolone, codeine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
  
  brexanolone, chlorpheniramine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (2)brexpiprazole and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  brexpiprazole and codeine both increase sedation. Use Caution/Monitor.

• brimonidine

  Monitor Closely (1)brimonidine and chlorpheniramine both increase sedation. Use Caution/Monitor.Minor (2)brimonidine increases effects of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
  
  brimonidine increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.Serious - Use Alternative (1)brimonidine and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• brivaracetam

  Monitor Closely (2)brivaracetam and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  brivaracetam and codeine both increase sedation. Use Caution/Monitor.

• bromocriptine

  Monitor Closely (1)bromocriptine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Hypertension, V tach.

• brompheniramine

  Monitor Closely (3)brompheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  brompheniramine and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  brompheniramine and codeine both increase sedation. Use Caution/Monitor.

• buprenorphine

  Monitor Closely (2)buprenorphine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and buprenorphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine buccal

  Monitor Closely (3)chlorpheniramine and buprenorphine buccal both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal and codeine both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine buccal, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• buprenorphine subdermal implant

  Serious - Use Alternative (2)buprenorphine subdermal implant and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine subdermal implant and codeine 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)buprenorphine transdermal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine transdermal and chlorpheniramine 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)codeine 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 (2)buprenorphine, long-acting injection and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  buprenorphine, long-acting injection and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bupropion

  Monitor Closely (1)bupropion will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents the conversion of codeine to its active metabolite morphine.

• butabarbital

  Monitor Closely (3)butabarbital and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and butabarbital both increase sedation. Use Caution/Monitor.
  
  butabarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• butalbital

  Monitor Closely (3)chlorpheniramine and butalbital both increase sedation. Use Caution/Monitor.
  
  butalbital and codeine both increase sedation. Use Caution/Monitor.
  
  butalbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• butorphanol

  Monitor Closely (3)butorphanol and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and butorphanol both increase sedation. Use Caution/Monitor.
  
  butorphanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)butorphanol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• cabergoline

  Serious - Use Alternative (1)cabergoline, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• caffeine

  Monitor Closely (3)chlorpheniramine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  caffeine and phenylephrine both decrease sedation. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (2)chlorpheniramine, calcium/magnesium/potassium/sodium oxybates. Either increases effects 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.
  
  codeine, calcium/magnesium/potassium/sodium oxybates. Either increases effects 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.

• carbinoxamine

  Monitor Closely (3)carbinoxamine and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  carbinoxamine and codeine both increase sedation. Use Caution/Monitor.
  
  carbinoxamine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (2)carisoprodol and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and carisoprodol both increase sedation. Use Caution/Monitor.

• celecoxib

  Monitor Closely (1)celecoxib decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cenobamate

  Monitor Closely (3)cenobamate, chlorpheniramine. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate, codeine. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

• chloral hydrate

  Monitor Closely (3)chloral hydrate and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and chloral hydrate both increase sedation. Use Caution/Monitor.
  
  chloral hydrate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (3)chlorpheniramine and chlordiazepoxide both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and codeine both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chloroquine

  Monitor Closely (1)chloroquine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• chlorpheniramine

  Monitor Closely (2)chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (5)chlorpromazine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine
  
  chlorpheniramine and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  codeine and chlorpromazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  chlorpromazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chlorzoxazone

  Monitor Closely (2)chlorzoxazone and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and chlorzoxazone both increase sedation. Use Caution/Monitor.

• cimetidine

  Monitor Closely (1)cimetidine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cinacalcet

  Monitor Closely (1)cinacalcet decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cinnarizine

  Monitor Closely (3)chlorpheniramine and cinnarizine both increase sedation. Use Caution/Monitor.
  
  cinnarizine and codeine both increase sedation. Use Caution/Monitor.
  
  cinnarizine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clemastine

  Monitor Closely (3)chlorpheniramine and clemastine both increase sedation. Use Caution/Monitor.
  
  clemastine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clemastine and codeine both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (3)chlorpheniramine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  codeine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  clobazam decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• clomipramine

  Monitor Closely (4)codeine and clomipramine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and clomipramine both increase sedation. Use Caution/Monitor.
  
  clomipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  clomipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)clomipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• clonazepam

  Monitor Closely (3)chlorpheniramine and clonazepam both increase sedation. Use Caution/Monitor.
  
  clonazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  clonazepam and codeine both increase sedation. Use Caution/Monitor.

• clonidine

  Serious - Use Alternative (1)clonidine, codeine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.

• clorazepate

  Monitor Closely (3)clorazepate and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and clorazepate both increase sedation. Use Caution/Monitor.
  
  clorazepate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• clozapine

  Monitor Closely (4)codeine and clozapine both increase sedation. Use Caution/Monitor.
  
  clozapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and clozapine both increase sedation. Use Caution/Monitor.
  
  clozapine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• cocaine topical

  Monitor Closely (1)cocaine topical decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• codeine

  Monitor Closely (2)chlorpheniramine and codeine both increase sedation. Use Caution/Monitor.
  
  codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• crofelemer

  Monitor Closely (1)crofelemer increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.

• cyclizine

  Monitor Closely (3)cyclizine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and cyclizine both increase sedation. Use Caution/Monitor.
  
  cyclizine and codeine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (2)chlorpheniramine and cyclobenzaprine both increase sedation. Use Caution/Monitor.
  
  cyclobenzaprine and codeine both increase sedation. Use Caution/Monitor.

• cyclophosphamide

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

• cyproheptadine

  Monitor Closely (3)cyproheptadine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and cyproheptadine both increase sedation. Use Caution/Monitor.
  
  cyproheptadine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dacomitinib

  Serious - Use Alternative (1)dacomitinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• dantrolene

  Monitor Closely (2)chlorpheniramine and dantrolene both increase sedation. Use Caution/Monitor.
  
  dantrolene and codeine both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (2)chlorpheniramine 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.
  
  codeine 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.

• darifenacin

  Monitor Closely (1)darifenacin decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• desflurane

  Monitor Closely (2)desflurane and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  desflurane and codeine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required. Serious - Use Alternative (2)desflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.
  
  desflurane increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• desipramine

  Monitor Closely (4)chlorpheniramine and desipramine both increase sedation. Use Caution/Monitor.
  
  codeine and desipramine both increase sedation. Use Caution/Monitor.
  
  desipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  desipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)desipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• desmopressin

  Minor (1)desmopressin increases effects of phenylephrine by pharmacodynamic synergism. Minor/Significance Unknown.

• desvenlafaxine

  Monitor Closely (1)desvenlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

• deutetrabenazine

  Monitor Closely (2)chlorpheniramine and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  codeine and deutetrabenazine both increase sedation. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (3)dexchlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and dexchlorpheniramine both increase sedation. Use Caution/Monitor.
  
  dexchlorpheniramine and codeine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (4)chlorpheniramine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexfenfluramine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  dexfenfluramine and phenylephrine both decrease sedation. Use Caution/Monitor.

• dexmedetomidine

  Monitor Closely (3)dexmedetomidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and dexmedetomidine both increase sedation. Use Caution/Monitor.
  
  dexmedetomidine and codeine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (4)dexmethylphenidate and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dexmethylphenidate and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (4)dextroamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dextroamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.Minor (1)dextroamphetamine increases effects of codeine by unspecified interaction mechanism. Minor/Significance Unknown.

• dextromoramide

  Monitor Closely (3)chlorpheniramine and dextromoramide both increase sedation. Use Caution/Monitor.
  
  codeine and dextromoramide both increase sedation. Use Caution/Monitor.
  
  dextromoramide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diamorphine

  Monitor Closely (3)chlorpheniramine and diamorphine both increase sedation. Use Caution/Monitor.
  
  codeine and diamorphine both increase sedation. Use Caution/Monitor.
  
  diamorphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• diazepam

  Monitor Closely (2)chlorpheniramine and diazepam both increase sedation. Use Caution/Monitor.
  
  diazepam and codeine both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (1)diazepam intranasal, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.Serious - Use Alternative (1)diazepam intranasal, codeine. 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.

• diethylpropion

  Monitor Closely (4)codeine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  diethylpropion and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  diethylpropion and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  Monitor Closely (2)difelikefalin and codeine both increase sedation. Use Caution/Monitor.
  
  difelikefalin and chlorpheniramine both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (3)difenoxin hcl increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and difenoxin hcl both increase sedation. Use Caution/Monitor.
  
  codeine and difenoxin hcl both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  Serious - Use Alternative (1)dihydroergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dihydroergotamine intranasal

  Serious - Use Alternative (1)dihydroergotamine intranasal, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• dimenhydrinate

  Monitor Closely (3)dimenhydrinate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and dimenhydrinate both increase sedation. Use Caution/Monitor.
  
  dimenhydrinate and codeine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (4)diphenhydramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  diphenhydramine and codeine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and diphenhydramine both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (3)codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.
  
  diphenoxylate hcl increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dipipanone

  Monitor Closely (3)chlorpheniramine and dipipanone both increase sedation. Use Caution/Monitor.
  
  codeine and dipipanone both increase sedation. Use Caution/Monitor.
  
  dipipanone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dobutamine

  Monitor Closely (4)codeine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dobutamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dobutamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• donepezil transdermal

  Monitor Closely (1)donepezil transdermal, chlorpheniramine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

• dopamine

  Monitor Closely (4)codeine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dopamine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  dopamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• dopexamine

  Monitor Closely (4)chlorpheniramine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dopexamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  dopexamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• dosulepin

  Monitor Closely (2)chlorpheniramine and dosulepin both increase sedation. Use Caution/Monitor.
  
  codeine and dosulepin both increase sedation. Use Caution/Monitor.

• doxapram

  Serious - Use Alternative (1)doxapram increases effects of phenylephrine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive pressor effect.

• doxazosin

  Minor (1)doxazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• doxepin

  Monitor Closely (3)codeine and doxepin both increase sedation. Use Caution/Monitor.
  
  doxepin increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and doxepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)doxepin, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• doxylamine

  Monitor Closely (2)doxylamine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and doxylamine both increase sedation. Use Caution/Monitor.

• dronedarone

  Monitor Closely (1)dronedarone decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• droperidol

  Monitor Closely (3)codeine and droperidol both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and droperidol both increase sedation. Use Caution/Monitor.
  
  droperidol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• droxidopa

  Monitor Closely (1)phenylephrine and droxidopa both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. May increase risk for supine hypertension

• duloxetine

  Monitor Closely (1)duloxetine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• efavirenz

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

• elagolix

  Monitor Closely (1)elagolix will decrease the level or effect of chlorpheniramine 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.

• eluxadoline

  Serious - Use Alternative (2)chlorpheniramine, 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.
  
  codeine, 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. .

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (2)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• ephedrine

  Monitor Closely (5)ephedrine, phenylephrine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.
  
  ephedrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  ephedrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  Monitor Closely (4)epinephrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  epinephrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine inhaled

  Monitor Closely (1)phenylephrine, epinephrine inhaled. Either increases effects of the other by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• epinephrine racemic

  Monitor Closely (4)chlorpheniramine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  epinephrine racemic and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  epinephrine racemic and phenylephrine both decrease sedation. Use Caution/Monitor.

• ergoloid mesylates

  Serious - Use Alternative (1)ergoloid mesylates, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• ergotamine

  Serious - Use Alternative (1)ergotamine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• esketamine intranasal

  Monitor Closely (2)esketamine intranasal, chlorpheniramine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
  
  esketamine intranasal, codeine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• estazolam

  Monitor Closely (3)estazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  estazolam and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and estazolam both increase sedation. Use Caution/Monitor.

• ethanol

  Monitor Closely (3)ethanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and ethanol both increase sedation. Use Caution/Monitor.
  
  codeine and ethanol both increase sedation. Use Caution/Monitor.

• ether

  Serious - Use Alternative (1)ether increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• etomidate

  Monitor Closely (2)etomidate and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  etomidate and codeine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)etomidate increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• eucalyptus

  Minor (3)eucalyptus increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  codeine and eucalyptus both increase sedation. Minor/Significance Unknown.
  
  chlorpheniramine and eucalyptus both increase sedation. Minor/Significance Unknown.

• fedratinib

  Monitor Closely (2)fedratinib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
  
  fedratinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• fenfluramine

  Monitor Closely (4)fenfluramine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  fenfluramine and phenylephrine both decrease sedation. Use Caution/Monitor.

• fentanyl

  Monitor Closely (1)fentanyl, 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 (3)fentanyl and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl, 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 intranasal

  Monitor Closely (1)fentanyl intranasal, 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 (3)fentanyl intranasal, 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 intranasal and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl intranasal and chlorpheniramine 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 (2)fentanyl iontophoretic transdermal system and codeine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  fentanyl iontophoretic transdermal system and chlorpheniramine both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transdermal

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

• fentanyl transmucosal

  Monitor Closely (1)fentanyl transmucosal, 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 transmucosal, 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.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole will increase the level or effect of chlorpheniramine 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.

• flibanserin

  Monitor Closely (2)chlorpheniramine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
  
  codeine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.

• fluoxetine

  Monitor Closely (1)fluoxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphineMinor (1)fluoxetine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• fluphenazine

  Monitor Closely (4)fluphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and fluphenazine both increase sedation. Use Caution/Monitor.
  
  fluphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  codeine and fluphenazine both increase sedation. Use Caution/Monitor.

• flurazepam

  Monitor Closely (3)chlorpheniramine and flurazepam both increase sedation. Use Caution/Monitor.
  
  flurazepam and codeine both increase sedation. Use Caution/Monitor.
  
  flurazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• formoterol

  Monitor Closely (4)chlorpheniramine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  formoterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  formoterol and phenylephrine both decrease sedation. Use Caution/Monitor.

• fosphenytoin

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

• gabapentin

  Monitor Closely (2)gabapentin, codeine. 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, chlorpheniramine. 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

  Monitor Closely (2)gabapentin enacarbil, codeine. 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, chlorpheniramine. 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 (2)codeine and ganaxolone both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and ganaxolone both increase sedation. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (1)givosiran will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• glycopyrronium tosylate topical

  Monitor Closely (1)glycopyrronium tosylate topical, chlorpheniramine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

• gotu kola

  Monitor Closely (1)gotu kola increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• haloperidol

  Monitor Closely (4)haloperidol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and haloperidol both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and haloperidol both increase sedation. Use Caution/Monitor.
  
  haloperidol decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• hawthorn

  Monitor Closely (1)hawthorn increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hops

  Monitor Closely (1)hops increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• hyaluronidase

  Monitor Closely (1)chlorpheniramine decreases effects of hyaluronidase by Other (see comment). Use Caution/Monitor. Comment: Antihistamines, when given in large systemic doses, may render tissues partially resistant to the action of hyaluronidase. Patients may require larger amounts of hyaluronidase for equivalent dispersing effect.

• hydralazine

  Monitor Closely (1)hydralazine, phenylephrine. Mechanism: pharmacodynamic antagonism. Use Caution/Monitor. Sympathomimetics can antagonize the activity of some antihypertensive agents.

• hydrocodone

  Serious - Use Alternative (1)hydrocodone, codeine. 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.

• hydromorphone

  Monitor Closely (3)chlorpheniramine and hydromorphone both increase sedation. Use Caution/Monitor.
  
  codeine and hydromorphone both increase sedation. Use Caution/Monitor.
  
  hydromorphone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydroxyzine

  Monitor Closely (3)chlorpheniramine and hydroxyzine both increase sedation. Use Caution/Monitor.
  
  hydroxyzine and codeine both increase sedation. Use Caution/Monitor.
  
  hydroxyzine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• idelalisib

  Serious - Use Alternative (1)idelalisib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates

• iloperidone

  Monitor Closely (4)codeine and iloperidone both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and iloperidone both increase sedation. Use Caution/Monitor.
  
  iloperidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  iloperidone increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

• imatinib

  Minor (2)imatinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  imatinib decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• imipramine

  Monitor Closely (4)codeine and imipramine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and imipramine both increase sedation. Use Caution/Monitor.
  
  imipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  imipramine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (1)imipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• indacaterol, inhaled

  Monitor Closely (1)phenylephrine increases effects of indacaterol, inhaled by Other (see comment). Use Caution/Monitor. Comment: If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of indacaterol may be potentiated.

• insulin degludec

  Monitor Closely (1)phenylephrine decreases effects of insulin degludec by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• insulin degludec/insulin aspart

  Monitor Closely (1)phenylephrine decreases effects of insulin degludec/insulin aspart by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• insulin inhaled

  Monitor Closely (1)phenylephrine decreases effects of insulin inhaled by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Sympathomimetics increase blood glucose by stimulating alpha and beta receptors; this action results in increased hepatic glucose production, glycogenolysis, and decreased insulin secretion.

• iobenguane I 123

  Contraindicated (1)phenylephrine decreases effects of iobenguane I 123 by receptor binding competition. Contraindicated. If clinically appropriate, discontinue drugs that compete for NE receptor sites for at least 5 half-lives; may cause false-negative imaging results.

• isocarboxazid

  Contraindicated (1)isocarboxazid increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (2)isocarboxazid increases effects of chlorpheniramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Isocarboxazid should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
  
  isocarboxazid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• isoflurane

  Serious - Use Alternative (1)isoflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• isoniazid

  Monitor Closely (1)isoniazid decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• isoproterenol

  Monitor Closely (4)codeine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  isoproterenol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  isoproterenol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of chlorpheniramine 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.

• kava

  Monitor Closely (1)kava increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• ketamine

  Monitor Closely (2)ketamine and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  ketamine and codeine both increase sedation. Use Caution/Monitor.

• ketoconazole

  Monitor Closely (1)ketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• ketotifen, ophthalmic

  Monitor Closely (3)chlorpheniramine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  codeine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  ketotifen, ophthalmic increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• larotrectinib

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

• lasmiditan

  Monitor Closely (2)lasmiditan, chlorpheniramine. 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.
  
  lasmiditan, codeine. 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)lemborexant, codeine. 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.
  
  lemborexant, chlorpheniramine. 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 chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

• letermovir

  Monitor Closely (2)letermovir increases levels of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  letermovir increases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (4)chlorpheniramine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  levalbuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  levalbuterol and phenylephrine both decrease sedation. Use Caution/Monitor.

• levoketoconazole

  Monitor Closely (1)levoketoconazole decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (1)levoketoconazole will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• levorphanol

  Monitor Closely (3)levorphanol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and levorphanol both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and levorphanol both increase sedation. Use Caution/Monitor.

• lidocaine

  Minor (1)lidocaine increases toxicity of codeine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

• linezolid

  Contraindicated (1)linezolid increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)linezolid increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• lisdexamfetamine

  Monitor Closely (4)lisdexamfetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  lisdexamfetamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• lofepramine

  Monitor Closely (3)chlorpheniramine and lofepramine both increase sedation. Use Caution/Monitor.
  
  codeine and lofepramine both increase sedation. Use Caution/Monitor.
  
  lofepramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)lofepramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• lofexidine

  Monitor Closely (3)codeine and lofexidine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and lofexidine both increase sedation. Use Caution/Monitor.
  
  lofexidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lonafarnib

  Serious - Use Alternative (1)lonafarnib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.

• lopinavir

  Monitor Closely (1)lopinavir decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• loprazolam

  Monitor Closely (3)loprazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and loprazolam both increase sedation. Use Caution/Monitor.
  
  loprazolam and codeine both increase sedation. Use Caution/Monitor.

• lorazepam

  Monitor Closely (3)chlorpheniramine and lorazepam both increase sedation. Use Caution/Monitor.
  
  lorazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  lorazepam and codeine both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (1)lorcaserin will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• lormetazepam

  Monitor Closely (3)lormetazepam and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and lormetazepam both increase sedation. Use Caution/Monitor.
  
  lormetazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine

  Monitor Closely (3)chlorpheniramine and loxapine both increase sedation. Use Caution/Monitor.
  
  codeine and loxapine both increase sedation. Use Caution/Monitor.
  
  loxapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (3)loxapine inhaled increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and loxapine inhaled both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and loxapine inhaled both increase sedation. Use Caution/Monitor.

• lumefantrine

  Monitor Closely (1)lumefantrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lurasidone

  Monitor Closely (2)lurasidone, chlorpheniramine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
  
  lurasidone, codeine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• maprotiline

  Monitor Closely (3)maprotiline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and maprotiline both increase sedation. Use Caution/Monitor.
  
  codeine and maprotiline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)maprotiline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• maraviroc

  Minor (1)maraviroc will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (3)chlorpheniramine and marijuana both increase sedation. Use Caution/Monitor.
  
  codeine and marijuana both increase sedation. Use Caution/Monitor.
  
  marijuana increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• melatonin

  Monitor Closely (3)melatonin increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and melatonin both increase sedation. Use Caution/Monitor.
  
  codeine and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (3)codeine and meperidine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and meperidine both increase sedation. Use Caution/Monitor.
  
  meperidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• meprobamate

  Monitor Closely (3)meprobamate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and meprobamate both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and meprobamate both increase sedation. Use Caution/Monitor.

• metaproterenol

  Monitor Closely (4)metaproterenol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  metaproterenol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  Monitor Closely (2)chlorpheniramine and metaxalone both increase sedation. Use Caution/Monitor.
  
  metaxalone and codeine both increase sedation. Use Caution/Monitor.

• methadone

  Monitor Closely (3)chlorpheniramine and methadone both increase sedation. Use Caution/Monitor.
  
  codeine and methadone both increase sedation. Use Caution/Monitor.
  
  methadone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (4)chlorpheniramine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  methamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  methamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• methocarbamol

  Monitor Closely (2)chlorpheniramine and methocarbamol both increase sedation. Use Caution/Monitor.
  
  methocarbamol and codeine both increase sedation. Use Caution/Monitor.

• methoxyflurane

  Serious - Use Alternative (1)methoxyflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• methyldopa

  Monitor Closely (1)methyldopa increases effects of phenylephrine by unknown mechanism. Use Caution/Monitor.

• methylene blue

  Serious - Use Alternative (1)methylene blue and codeine both increase serotonin levels. Avoid or Use Alternate Drug. If drug combination must be administered, monitor for evidence of serotonergic or opioid-related toxicities

• methylenedioxymethamphetamine

  Monitor Closely (4)chlorpheniramine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  methylenedioxymethamphetamine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  methylenedioxymethamphetamine and phenylephrine both decrease sedation. Use Caution/Monitor.

• methylergonovine

  Serious - Use Alternative (1)methylergonovine, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Additive vasospasm; risk of hypertension.

• metoclopramide intranasal

  Serious - Use Alternative (2)chlorpheniramine, 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.
  
  codeine, 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.

• midazolam

  Monitor Closely (3)midazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and midazolam both increase sedation. Use Caution/Monitor.
  
  midazolam and codeine both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (2)midazolam intranasal, codeine. Either increases effects 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.
  
  midazolam intranasal, chlorpheniramine. Either increases effects 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.

• midodrine

  Monitor Closely (4)codeine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  midodrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  midodrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• mirabegron

  Monitor Closely (1)mirabegron will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  Monitor Closely (3)chlorpheniramine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  codeine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  mirtazapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mitotane

  Monitor Closely (1)mitotane decreases levels of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

• modafinil

  Monitor Closely (3)codeine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  modafinil and phenylephrine both decrease sedation. Use Caution/Monitor.

• morphine

  Monitor Closely (3)chlorpheniramine and morphine both increase sedation. Use Caution/Monitor.
  
  codeine and morphine both increase sedation. Use Caution/Monitor.
  
  morphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• motherwort

  Monitor Closely (3)chlorpheniramine and motherwort both increase sedation. Use Caution/Monitor.
  
  codeine and motherwort both increase sedation. Use Caution/Monitor.
  
  motherwort increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moxisylyte

  Minor (1)moxisylyte, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• moxonidine

  Monitor Closely (3)codeine and moxonidine both increase sedation. Use Caution/Monitor.
  
  moxonidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (3)codeine and nabilone both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and nabilone both increase sedation. Use Caution/Monitor.
  
  nabilone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nadolol

  Monitor Closely (1)nadolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• nalbuphine

  Monitor Closely (3)codeine and nalbuphine both increase sedation. Use Caution/Monitor.
  
  nalbuphine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and nalbuphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)nalbuphine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• nettle

  Minor (1)nettle increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. (High dose nettle; theoretical interaction) May enhance CNS depression.

• nilotinib

  Minor (1)nilotinib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (4)norepinephrine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  codeine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  norepinephrine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nortriptyline

  Monitor Closely (3)codeine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• olanzapine

  Monitor Closely (3)codeine and olanzapine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and olanzapine both increase sedation. Use Caution/Monitor.
  
  olanzapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oliceridine

  Monitor Closely (1)oliceridine, codeine. 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.

• olodaterol inhaled

  Monitor Closely (1)phenylephrine and olodaterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Caution with coadministration of adrenergic drugs by any route because of additive sympathetic effects

• olopatadine intranasal

  Serious - Use Alternative (2)chlorpheniramine 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.
  
  codeine 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.

• opium tincture

  Monitor Closely (3)chlorpheniramine and opium tincture both increase sedation. Use Caution/Monitor.
  
  codeine and opium tincture both increase sedation. Use Caution/Monitor.
  
  opium tincture increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (2)orphenadrine and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and orphenadrine both increase sedation. Use Caution/Monitor.

• oxazepam

  Monitor Closely (3)oxazepam and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and oxazepam both increase sedation. Use Caution/Monitor.
  
  oxazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• oxycodone

  Monitor Closely (3)oxycodone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and oxycodone both increase sedation. Use Caution/Monitor.
  
  codeine and oxycodone both increase sedation. Use Caution/Monitor.

• oxymetazoline topical

  Monitor Closely (1)oxymetazoline topical and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• oxymorphone

  Monitor Closely (3)oxymorphone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and oxymorphone both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and oxymorphone both increase sedation. Use Caution/Monitor.

• oxytocin

  Monitor Closely (1)oxytocin increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor.

• ozanimod

  Serious - Use Alternative (1)ozanimod and codeine 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 (3)chlorpheniramine and paliperidone both increase sedation. Use Caution/Monitor.
  
  codeine and paliperidone both increase sedation. Use Caution/Monitor.
  
  paliperidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• papaveretum

  Monitor Closely (3)codeine and papaveretum both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and papaveretum both increase sedation. Use Caution/Monitor.
  
  papaveretum increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• papaverine

  Monitor Closely (2)chlorpheniramine and papaverine both increase sedation. Use Caution/Monitor.
  
  codeine and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Minor (1)parecoxib will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• paroxetine

  Monitor Closely (1)paroxetine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• passion flower

  Monitor Closely (1)passion flower increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.

• peginterferon alfa 2b

  Monitor Closely (1)peginterferon alfa 2b, codeine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

• pegvisomant

  Monitor Closely (1)codeine decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

• pentazocine

  Monitor Closely (3)chlorpheniramine and pentazocine both increase sedation. Use Caution/Monitor.
  
  codeine and pentazocine both increase sedation. Use Caution/Monitor.
  
  pentazocine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)pentazocine, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

• pentobarbital

  Monitor Closely (3)chlorpheniramine and pentobarbital both increase sedation. Use Caution/Monitor.
  
  pentobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  pentobarbital and codeine both increase sedation. Use Caution/Monitor.

• perampanel

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

• perphenazine

  Monitor Closely (4)perphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  chlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.Minor (2)perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• phendimetrazine

  Monitor Closely (4)codeine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phendimetrazine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  phendimetrazine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• phenelzine

  Contraindicated (1)phenelzine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Monitor Closely (1)phenelzine increases effects of chlorpheniramine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Coadministration of phenelzine and antihistamines may result in additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .Serious - Use Alternative (1)phenelzine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• phenobarbital

  Monitor Closely (3)phenobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and phenobarbital both increase sedation. Use Caution/Monitor.
  
  phenobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenoxybenzamine

  Minor (1)phenoxybenzamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• phentermine

  Monitor Closely (4)phentermine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phentermine and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• phentolamine

  Minor (1)phentolamine, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• phenylephrine

  Monitor Closely (2)chlorpheniramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine PO

  Monitor Closely (2)codeine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
  
  chlorpheniramine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• pholcodine

  Monitor Closely (3)pholcodine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and pholcodine both increase sedation. Use Caution/Monitor.
  
  codeine and pholcodine both increase sedation. Use Caution/Monitor.

• pimozide

  Monitor Closely (3)codeine and pimozide both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and pimozide both increase sedation. Use Caution/Monitor.
  
  pimozide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pindolol

  Monitor Closely (1)pindolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• pirbuterol

  Monitor Closely (4)codeine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  pirbuterol and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  pirbuterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• prasugrel

  Serious - Use Alternative (1)codeine will decrease the level or effect of prasugrel by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of prasugrel and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

• prazosin

  Minor (1)prazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• pregabalin

  Monitor Closely (2)pregabalin, codeine. 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.
  
  pregabalin, chlorpheniramine. 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

  Monitor Closely (3)primidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and primidone both increase sedation. Use Caution/Monitor.
  
  primidone and codeine both increase sedation. Use Caution/Monitor.

• procarbazine

  Contraindicated (1)procarbazine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)procarbazine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. MAOIs may potentiate CNS depression and hypotension. Do not use within 14 days of MAOI use. .

• prochlorperazine

  Monitor Closely (4)chlorpheniramine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  codeine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  prochlorperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  prochlorperazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• promazine

  Monitor Closely (1)promazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• promethazine

  Monitor Closely (4)promethazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and promethazine both increase sedation. Use Caution/Monitor.
  
  promethazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  promethazine and codeine both increase sedation. Use Caution/Monitor.

• propafenone

  Minor (2)propafenone will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  propafenone decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• propofol

  Monitor Closely (3)propofol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  propofol and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  propofol and codeine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)propofol increases levels of phenylephrine by decreasing metabolism. Contraindicated.

• propranolol

  Monitor Closely (1)propranolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• propylhexedrine

  Monitor Closely (4)codeine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phenylephrine and propylhexedrine both decrease sedation. Use Caution/Monitor.
  
  chlorpheniramine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phenylephrine and propylhexedrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• protriptyline

  Monitor Closely (3)chlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.
  
  codeine and protriptyline both increase sedation. Use Caution/Monitor.
  
  protriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• pseudoephedrine

  Monitor Closely (1)phenylephrine and pseudoephedrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• quazepam

  Monitor Closely (3)chlorpheniramine and quazepam both increase sedation. Use Caution/Monitor.
  
  quazepam and codeine both increase sedation. Use Caution/Monitor.
  
  quazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quetiapine

  Monitor Closely (3)codeine and quetiapine both increase sedation. Use Caution/Monitor.
  
  quetiapine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and quetiapine both increase sedation. Use Caution/Monitor.

• quinacrine

  Minor (2)quinacrine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  quinacrine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• quinidine

  Monitor Closely (1)quinidine will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• ramelteon

  Monitor Closely (2)chlorpheniramine and ramelteon both increase sedation. Use Caution/Monitor.
  
  codeine and ramelteon both increase sedation. Use Caution/Monitor.

• ranolazine

  Minor (1)ranolazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rasagiline

  Monitor Closely (1)rasagiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.Serious - Use Alternative (1)rasagiline increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• remimazolam

  Monitor Closely (1)remimazolam, codeine. 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.

• ribociclib

  Monitor Closely (1)ribociclib will increase the level or effect of codeine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ribociclib will increase the level or effect of chlorpheniramine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• risperidone

  Monitor Closely (3)codeine and risperidone both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and risperidone both increase sedation. Use Caution/Monitor.
  
  risperidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ritonavir

  Monitor Closely (1)ritonavir will decrease the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• rolapitant

  Monitor Closely (1)rolapitant will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• rucaparib

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

• safinamide

  Monitor Closely (1)phenylephrine and safinamide both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Monitor patients for hypertension if safinamide is prescribed concomitantly with prescription or nonprescription sympathomimetics, including nasal, oral, or ophthalmic decongestants and cold remedies.

• sage

  Minor (3)codeine and sage both increase sedation. Minor/Significance Unknown.
  
  sage increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Minor/Significance Unknown.
  
  chlorpheniramine and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (4)chlorpheniramine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  salmeterol and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  salmeterol and phenylephrine both decrease sedation. Use Caution/Monitor.

• scullcap

  Monitor Closely (3)codeine and scullcap both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and scullcap both increase sedation. Use Caution/Monitor.
  
  scullcap increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• secobarbital

  Monitor Closely (3)secobarbital increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  secobarbital and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and secobarbital both increase sedation. Use Caution/Monitor.

• selegiline

  Monitor Closely (2)selegiline increases toxicity of codeine by unknown mechanism. Modify Therapy/Monitor Closely. Potential for increased CNS depression, drowsiness, dizziness or hypotension, so use with any MAOI should be cautious.
  
  selegiline increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode.

• selegiline transdermal

  Contraindicated (1)selegiline transdermal increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Serious - Use Alternative (1)selegiline transdermal increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

• selinexor

  Serious - Use Alternative (1)selinexor, codeine. 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.

• serdexmethylphenidate/dexmethylphenidate

  Monitor Closely (2)serdexmethylphenidate/dexmethylphenidate and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  serdexmethylphenidate/dexmethylphenidate and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• sertraline

  Monitor Closely (1)sertraline decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Minor (1)sertraline decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• sevoflurane

  Monitor Closely (2)sevoflurane and chlorpheniramine both increase sedation. Use Caution/Monitor.
  
  sevoflurane and codeine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)sevoflurane increases levels of phenylephrine by decreasing metabolism. Contraindicated.
  
  sevoflurane increases toxicity of phenylephrine by Mechanism: unknown. Avoid or Use Alternate Drug. Risk of V tach, HTN.

• shepherd's purse

  Monitor Closely (3)chlorpheniramine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  codeine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  shepherd's purse increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• Siberian ginseng

  Minor (1)Siberian ginseng increases effects of chlorpheniramine by pharmacodynamic synergism. Minor/Significance Unknown. May enhance CNS depression.

• silodosin

  Minor (1)silodosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• sodium oxybate

  Serious - Use Alternative (2)chlorpheniramine, sodium oxybate. Either increases effects 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.
  
  codeine, sodium oxybate. Either increases effects 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.

• solriamfetol

  Monitor Closely (1)phenylephrine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• stiripentol

  Monitor Closely (2)stiripentol, codeine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
  
  stiripentol, chlorpheniramine. 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.

• sufentanil

  Monitor Closely (3)codeine and sufentanil both increase sedation. Use Caution/Monitor.
  
  sufentanil increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and sufentanil both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Serious - Use Alternative (1)sufentanil SL, codeine. 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

  Monitor Closely (1)suvorexant and codeine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tapentadol

  Monitor Closely (3)codeine and tapentadol both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and tapentadol both increase sedation. Use Caution/Monitor.
  
  tapentadol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tazemetostat

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

• tecovirimat

  Monitor Closely (1)tecovirimat will decrease the level or effect of chlorpheniramine 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

  Monitor Closely (3)temazepam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and temazepam both increase sedation. Use Caution/Monitor.
  
  temazepam and codeine both increase sedation. Use Caution/Monitor.

• terazosin

  Minor (1)terazosin, phenylephrine. Either decreases effects of the other by Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown.

• terbinafine

  Monitor Closely (1)terbinafine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• terbutaline

  Monitor Closely (4)codeine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  terbutaline and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  terbutaline and phenylephrine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  chlorpheniramine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• thioridazine

  Monitor Closely (5)thioridazine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.
  
  codeine and thioridazine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and thioridazine both increase sedation. Use Caution/Monitor.
  
  thioridazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  thioridazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)thioridazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• thiothixene

  Monitor Closely (3)chlorpheniramine and thiothixene both increase sedation. Use Caution/Monitor.
  
  codeine and thiothixene both increase sedation. Use Caution/Monitor.
  
  thiothixene increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ticagrelor

  Serious - Use Alternative (1)codeine will decrease the level or effect of ticagrelor by inhibition of GI absorption. Applies only to oral form of both agents. Avoid or Use Alternate Drug. Co-administration of opioid agonists delay and reduce absorption of ticagrelor and its active metabolite presumably by slowing gastric emptying; consider the use of a parenteral anti-platelet agent in acute coronary syndrome patients requiring co-administration of opioid agonists

• ticlopidine

  Monitor Closely (1)ticlopidine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.

• timolol

  Monitor Closely (1)timolol increases effects of phenylephrine by pharmacodynamic synergism. Use Caution/Monitor. Risk of acute hypertensive episode (rare).

• tipranavir

  Minor (1)tipranavir will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• topiramate

  Monitor Closely (3)topiramate increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  codeine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
  
  chlorpheniramine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

  Monitor Closely (3)chlorpheniramine and tramadol both increase sedation. Use Caution/Monitor.
  
  codeine and tramadol both increase sedation. Use Caution/Monitor.
  
  tramadol increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)tramadol, codeine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

• tranylcypromine

  Contraindicated (1)tranylcypromine increases effects of phenylephrine by pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.Monitor Closely (1)tranylcypromine decreases effects of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Prevents conversion of codeine to its active metabolite morphine.Serious - Use Alternative (2)tranylcypromine increases effects of chlorpheniramine by Other (see comment). Avoid or Use Alternate Drug. Comment: Tranylcypromine should not be administered in combination with antihistamines because of potential additive CNS depressant effects. MAO inhibitors also prolong and intensify anticholinergic effects of antihistamines. .
  
  tranylcypromine increases toxicity of codeine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

• trazodone

  Monitor Closely (3)chlorpheniramine and trazodone both increase sedation. Use Caution/Monitor.
  
  codeine and trazodone both increase sedation. Use Caution/Monitor.
  
  trazodone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)trazodone, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• triazolam

  Monitor Closely (3)chlorpheniramine and triazolam both increase sedation. Use Caution/Monitor.
  
  triazolam increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  triazolam and codeine both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (3)triclofos and codeine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and triclofos both increase sedation. Use Caution/Monitor.
  
  triclofos increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (4)chlorpheniramine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  codeine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  trifluoperazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• trimipramine

  Monitor Closely (3)codeine and trimipramine both increase sedation. Use Caution/Monitor.
  
  trimipramine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)trimipramine, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• triprolidine

  Monitor Closely (3)triprolidine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and triprolidine both increase sedation. Use Caution/Monitor.
  
  triprolidine and codeine both increase sedation. Use Caution/Monitor.

• tucatinib

  Serious - Use Alternative (1)tucatinib will increase the level or effect of chlorpheniramine 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

  Monitor Closely (1)valerian increases effects of chlorpheniramine by pharmacodynamic synergism. Use Caution/Monitor. May enhance CNS depression.Serious - Use Alternative (1)valerian and codeine both increase sedation. Avoid or Use Alternate Drug.

• venlafaxine

  Monitor Closely (1)venlafaxine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)venlafaxine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• voxelotor

  Serious - Use Alternative (1)voxelotor will increase the level or effect of chlorpheniramine 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.

• xylometazoline

  Monitor Closely (4)chlorpheniramine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  codeine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  phenylephrine and xylometazoline both decrease sedation. Use Caution/Monitor.
  
  phenylephrine and xylometazoline both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

• yohimbe

  Serious - Use Alternative (1)yohimbe, phenylephrine. Mechanism: pharmacodynamic synergism. Contraindicated. Risk of acute hypertensive episode.

• yohimbine

  Monitor Closely (4)yohimbine and phenylephrine both decrease sedation. Use Caution/Monitor.
  
  phenylephrine and yohimbine both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.
  
  codeine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ziconotide

  Monitor Closely (3)codeine and ziconotide both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and ziconotide both increase sedation. Use Caution/Monitor.
  
  ziconotide increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)ziconotide, codeine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

• ziprasidone

  Monitor Closely (3)codeine and ziprasidone both increase sedation. Use Caution/Monitor.
  
  ziprasidone increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  chlorpheniramine and ziprasidone both increase sedation. Use Caution/Monitor.

• zotepine

  Monitor Closely (2)codeine and zotepine both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and zotepine both increase sedation. Use Caution/Monitor.