Dosing & Uses
Dosage Forms & Strengths
morphine/naltrexone
extended-release capsule: Schedule II
- 20mg/0.8mg
- 30mg/1.2mg
- 50mg/2mg
- 60mg/2.4mg
- 80mg/3.2mg
- 100mg/4mg
Chronic Severe Pain
Indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate
Opioid naïve: Initiate with lowest dose (ie, morphine/naltrexone 20 mg/0.8 mg PO q24hr); may adjust dose by titrating at 1-2 day intervals (steady-state plasma concentration are reached within 24-36 hr)
Conversion from other PO morphine: Administer one-half of daily dose q12hr OR administer total daily dose qDay
Conversion from PO opioids, parenteral morphine, or other parenteral opioids: Substantial inter-patient variation exist for conversion; for this reason, it is safer to underestimate patient’s 24-hour PO morphine dose during this transition and provide additional prompt-acting rescue analgesics until new daily dose established
Individualize dose
- Titrate no more frequently than q48hr to allow patient to stabilize before dose escalation
- For breakthrough pain, supplement with small dose (ie, <20% total daily dose) of short-acting analgesic
- If qDay dosing does not provide adequate analgesia, administer total daily dose divided q12hr
- Do not administer more frequently than q12hr
Opioid-tolerant definition
- Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression
- Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8 mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of another opioid
Limitations of use
- Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve for patients whom alternative treatment options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain
- Not indicated as a PRN analgesic
- Not indicated for acute/postoperative pain, mild pain, or short-term pain relief; only indicated for postoperative use if patient already receiving chronic opioid therapy prior to surgery, or if postoperative pain is expected to be moderate-to-severe and persist for an extended period of time
Renal Impairment
Caution in severe impairment; information on renal impairment dosing not available from the manufacturer
Hepatic Impairment
Caution in severe impairment; information on hepatic impairment dosing not available from the manufacturer
Administration
Swallow capsule whole; chewing, crushing, or dissolving contents of capsules will result in uncontrolled delivery of morphine and can lead to overdose or death
The capsules contain pellets that consist of morphine and sequestered naltrexone; the pellets in the capsules are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of morphine
Consuming capsules that have been altered by crushing, chewing, or dissolving the pellets can release sufficient naltrexone to precipitate withdrawal in opioid-dependent individuals
May sprinkle capsule contents on apple sauce and swallow immediately; do not chew; rinse the mouth to ensure all pellets have been swallowed
Do not administer pellets through a nasogastric or gastric tube
May administer qDay or q12hr; do not administer more frequently than q12hr
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (2)
- alvimopan
alvimopan, morphine. 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.
- safinamide
morphine, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.
Serious - Use Alternative (32)
- artemether/lumefantrine
artemether/lumefantrine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
- benzhydrocodone/acetaminophen
benzhydrocodone/acetaminophen, morphine. 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 morphine 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.
bremelanotide will decrease the level or effect of naltrexone 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 using bremelanotide with an orally administered naltrexone-containing product that is intended to treat alcohol and opioid addiction due to the potential for naltrexone treatment failure. - buprenorphine
buprenorphine, morphine. 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.
- naldemedine
naldemedine, naltrexone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive opioid receptor anatagonism and increased risk of opioid withdrawal.
- buprenorphine buccal
buprenorphine buccal, morphine. 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.
- butorphanol
butorphanol, morphine. 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.
- calcium/magnesium/potassium/sodium oxybates
morphine, 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.
- cimetidine
cimetidine increases effects of morphine by decreasing metabolism. Avoid or Use Alternate Drug.
- citalopram
morphine, citalopram. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
- clonidine
clonidine, morphine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration enhances CNS depressant effects.
- clopidogrel
morphine will decrease the level or effect of clopidogrel by Other (see comment). Avoid or Use Alternate Drug. coadministration of opioid agonists delay and reduce absorption of clopidogrel, presumably because of slowed gastric emptying, resulting in reduced exposure to its metabolites; consider use of parenteral antiplatelet agents in acute coronary syndrome patients requiring coadministration of morphine or other opioid agonists
- desvenlafaxine
morphine and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.
- diazepam intranasal
diazepam intranasal, morphine. 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.
- eluxadoline
morphine, 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. .
- erdafitinib
erdafitinib will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- escitalopram
morphine, escitalopram. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
- fentanyl
fentanyl, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fentanyl intranasal
fentanyl intranasal, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fentanyl transdermal
fentanyl transdermal, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fentanyl transmucosal
fentanyl transmucosal, morphine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.
- fluoxetine
fluoxetine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
morphine, fluoxetine. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. - hydrocodone
hydrocodone, morphine. 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.
- isocarboxazid
isocarboxazid and morphine both increase serotonin levels. Avoid or Use Alternate Drug.
isocarboxazid increases toxicity of morphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d. - lasmiditan
lasmiditan increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- linezolid
linezolid and morphine both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.
linezolid increases toxicity of morphine by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d. - lumefantrine
lumefantrine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
- methylene blue
methylene blue and morphine both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue morphine (if possible) and monitor for CNS toxicity. Morphine may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.
- metoclopramide intranasal
morphine, 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, morphine. 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.
- naloxegol
naloxegol, naltrexone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration; potential for additive effect of opioid receptor anatagonism and increased risk of opioid withdrawal.
- olopatadine intranasal
morphine 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.
Monitor Closely (145)
- 5-HTP
5-HTP and morphine both increase serotonin levels. Use Caution/Monitor.
- acamprosate
naltrexone increases levels of acamprosate by unspecified interaction mechanism. Use Caution/Monitor. No dosage adjustment is needed.
- albuterol
morphine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- alfentanil
alfentanil and morphine both increase sedation. Use Caution/Monitor.
- almotriptan
almotriptan and morphine both increase serotonin levels. Use Caution/Monitor.
- alprazolam
alprazolam and morphine both increase sedation. Use Caution/Monitor.
- amiodarone
amiodarone will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- amitriptyline
morphine and amitriptyline both increase sedation. Use Caution/Monitor.
amitriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. - amobarbital
amobarbital and morphine both increase sedation. Use Caution/Monitor.
- amoxapine
morphine and amoxapine both increase sedation. Use Caution/Monitor.
amoxapine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. - apalutamide
apalutamide will decrease the level or effect of naltrexone by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates.
apalutamide will decrease the level or effect of morphine by increasing elimination. Use Caution/Monitor. Apalutamide induces UGT and may decrease systemic exposure of drugs that are UGT substrates. - apomorphine
morphine and apomorphine both increase sedation. Use Caution/Monitor.
- dronabinol
naltrexone increases effects of dronabinol by Other (see comment). Use Caution/Monitor. Comment: Naltrexone may enhance therapeutic effects of cannabinoids. .
- arformoterol
morphine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- aripiprazole
morphine and aripiprazole both increase sedation. Use Caution/Monitor.
- armodafinil
morphine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- asenapine
asenapine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- azelastine
azelastine and morphine both increase sedation. Use Caution/Monitor.
- baclofen
baclofen and morphine both increase sedation. Use Caution/Monitor.
- belladonna and opium
morphine and belladonna and opium both increase sedation. Use Caution/Monitor.
- benperidol
morphine and benperidol both increase sedation. Use Caution/Monitor.
- benzphetamine
morphine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- berotralstat
berotralstat will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.
- brexanolone
brexanolone, morphine. Either increases toxicity of the other by sedation. Use Caution/Monitor.
- brompheniramine
brompheniramine and morphine both increase sedation. Use Caution/Monitor.
- buprenorphine
buprenorphine and morphine both increase sedation. Use Caution/Monitor.
- buprenorphine buccal
buprenorphine buccal and morphine both increase sedation. Use Caution/Monitor.
- buprenorphine, long-acting injection
morphine 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.
- bupropion
bupropion will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- buspirone
buspirone and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
- butabarbital
butabarbital and morphine both increase sedation. Use Caution/Monitor.
- butalbital
butalbital and morphine both increase sedation. Use Caution/Monitor.
- butorphanol
butorphanol and morphine both increase sedation. Use Caution/Monitor.
- caffeine
morphine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- cannabidiol
cannabidiol will increase the level or effect of morphine by Other (see comment). Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit UGT2B7 activity. Consider reducing the dose when concomitantly using UGT2B7 substrates.
- captopril
morphine, captopril. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Both drugs lower blood pressure. Monitor blood ressure.
- carbinoxamine
carbinoxamine and morphine both increase sedation. Use Caution/Monitor.
- carisoprodol
carisoprodol and morphine both increase sedation. Use Caution/Monitor.
- celecoxib
celecoxib will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- chloral hydrate
chloral hydrate and morphine both increase sedation. Use Caution/Monitor.
- chlordiazepoxide
chlordiazepoxide and morphine both increase sedation. Use Caution/Monitor.
- chloroquine
chloroquine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- chlorpheniramine
chlorpheniramine and morphine both increase sedation. Use Caution/Monitor.
- chlorpromazine
morphine and chlorpromazine both increase sedation. Use Caution/Monitor.
- chlorzoxazone
chlorzoxazone and morphine both increase sedation. Use Caution/Monitor.
- cimetidine
cimetidine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- cinnarizine
cinnarizine and morphine both increase sedation. Use Caution/Monitor.
- citalopram
citalopram and morphine both increase serotonin levels. Use Caution/Monitor. Combination may increase risk of serotonin syndrome or neuroleptic malignant syndrome-like reactions.
- clemastine
clemastine and morphine both increase sedation. Use Caution/Monitor.
- clobazam
morphine, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
- clomipramine
morphine and clomipramine both increase sedation. Use Caution/Monitor.
clomipramine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. - clonazepam
clonazepam and morphine both increase sedation. Use Caution/Monitor.
- clorazepate
clorazepate and morphine both increase sedation. Use Caution/Monitor.
- clozapine
morphine and clozapine both increase sedation. Use Caution/Monitor.
- cocaine topical
cocaine topical and morphine both increase serotonin levels. Use Caution/Monitor.
- codeine
codeine and morphine both increase sedation. Use Caution/Monitor.
- cyclizine
cyclizine and morphine both increase sedation. Use Caution/Monitor.
- cyclobenzaprine
cyclobenzaprine and morphine both increase sedation. Use Caution/Monitor.
- cyproheptadine
cyproheptadine and morphine both increase sedation. Use Caution/Monitor.
- dantrolene
dantrolene and morphine both increase sedation. Use Caution/Monitor.
- daridorexant
morphine 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 will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- desflurane
desflurane and morphine both increase sedation. Use Caution/Monitor. Opioids may decrease MAC requirements, less inhalation anesthetic may be required.
- desipramine
morphine and desipramine both increase sedation. Use Caution/Monitor.
desipramine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. - desvenlafaxine
desvenlafaxine will increase the level or effect of morphine 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
morphine and deutetrabenazine both increase sedation. Use Caution/Monitor.
- dexchlorpheniramine
dexchlorpheniramine and morphine both increase sedation. Use Caution/Monitor.
- dexfenfluramine
morphine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dexfenfluramine and morphine both increase serotonin levels. Use Caution/Monitor. - dexmedetomidine
dexmedetomidine and morphine both increase sedation. Use Caution/Monitor.
- dexmethylphenidate
morphine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dextroamphetamine
morphine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
dextroamphetamine and morphine both increase serotonin levels. Use Caution/Monitor. - dextromethorphan
dextromethorphan and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
- dextromoramide
dextromoramide and morphine both increase sedation. Use Caution/Monitor.
- diamorphine
diamorphine and morphine both increase sedation. Use Caution/Monitor.
- diazepam
diazepam and morphine both increase sedation. Use Caution/Monitor.
- dichlorphenamide
dichlorphenamide and morphine both decrease serum potassium. Use Caution/Monitor.
- diethylpropion
morphine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- difelikefalin
difelikefalin and morphine both increase sedation. Use Caution/Monitor.
- difenoxin hcl
difenoxin hcl and morphine both increase sedation. Use Caution/Monitor.
- dihydroergotamine
dihydroergotamine and morphine both increase serotonin levels. Use Caution/Monitor.
- dihydroergotamine intranasal
dihydroergotamine intranasal and morphine both increase serotonin levels. Use Caution/Monitor.
- dimenhydrinate
dimenhydrinate and morphine both increase sedation. Use Caution/Monitor.
- diphenhydramine
diphenhydramine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
diphenhydramine and morphine both increase sedation. Use Caution/Monitor. - diphenoxylate hcl
diphenoxylate hcl and morphine both increase sedation. Use Caution/Monitor.
- dipipanone
dipipanone and morphine both increase sedation. Use Caution/Monitor.
- dobutamine
morphine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dopamine
morphine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dopexamine
morphine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- dosulepin
morphine and dosulepin both increase sedation. Use Caution/Monitor.
- doxepin
morphine and doxepin both increase sedation. Use Caution/Monitor.
doxepin and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. - doxylamine
doxylamine and morphine both increase sedation. Use Caution/Monitor.
- dronedarone
dronedarone will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- droperidol
morphine and droperidol both increase sedation. Use Caution/Monitor.
- duloxetine
duloxetine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
duloxetine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. - elagolix
elagolix will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- eletriptan
eletriptan and morphine both increase serotonin levels. Use Caution/Monitor.
- eliglustat
eliglustat increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
- eltrombopag
eltrombopag increases levels of morphine by decreasing metabolism. Use Caution/Monitor. UGT inhibition; significance of interaction unclear.
- ephedrine
morphine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- epinephrine
morphine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- epinephrine racemic
morphine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- ergotamine
ergotamine and morphine both increase serotonin levels. Use Caution/Monitor.
- escitalopram
escitalopram and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
- esketamine intranasal
esketamine intranasal, morphine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.
- estazolam
estazolam and morphine both increase sedation. Use Caution/Monitor.
- ethanol
morphine and ethanol both increase sedation. Use Caution/Monitor.
- etomidate
etomidate and morphine both increase sedation. Use Caution/Monitor.
- fenfluramine
morphine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
fenfluramine and morphine both increase serotonin levels. Use Caution/Monitor. - flibanserin
morphine and flibanserin both increase sedation. Modify Therapy/Monitor Closely. Risk for sedation increased if flibanserin is coadministration with other CNS depressants.
- fluoxetine
fluoxetine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
- fluphenazine
morphine and fluphenazine both increase sedation. Use Caution/Monitor.
- flurazepam
flurazepam and morphine both increase sedation. Use Caution/Monitor.
- fluvoxamine
fluvoxamine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
- formoterol
morphine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- fostamatinib
fostamatinib will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp substrates. Monitor for toxicities of the P-gp substrate drug that may require dosage reduction when given concurrently with fostamatinib.
- frovatriptan
frovatriptan and morphine both increase serotonin levels. Use Caution/Monitor.
- gabapentin
gabapentin, morphine. Either increases effects of the other by Mechanism: 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, morphine. 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, morphine. 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
morphine and ganaxolone both increase sedation. Use Caution/Monitor.
- glecaprevir/pibrentasvir
glecaprevir/pibrentasvir will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- haloperidol
haloperidol will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
morphine and haloperidol both increase sedation. Use Caution/Monitor. - hydromorphone
hydromorphone and morphine both increase sedation. Use Caution/Monitor.
- hydroxyzine
hydroxyzine and morphine both increase sedation. Use Caution/Monitor.
- iloperidone
morphine and iloperidone both increase sedation. Use Caution/Monitor.
- imatinib
imatinib will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
- imipramine
morphine and imipramine both increase sedation. Use Caution/Monitor.
imipramine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. - isoniazid
isoniazid and morphine both increase serotonin levels. Use Caution/Monitor.
- isoproterenol
morphine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- istradefylline
istradefylline will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.
- ivacaftor
ivacaftor increases levels of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.
- ketamine
ketamine and morphine both increase sedation. Use Caution/Monitor.
- ketotifen, ophthalmic
morphine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
- L-tryptophan
L-tryptophan and morphine both increase serotonin levels. Use Caution/Monitor.
- lasmiditan
lasmiditan, morphine. 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, morphine. 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.
- levalbuterol
morphine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- levomilnacipran
levomilnacipran and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
- levonorgestrel oral/ethinylestradiol/ferrous bisglycinate
levonorgestrel oral/ethinylestradiol/ferrous bisglycinate will decrease the level or effect of morphine by unknown mechanism. Use Caution/Monitor.
- levorphanol
levorphanol and morphine both increase sedation. Use Caution/Monitor.
- lisdexamfetamine
morphine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
- lithium
lithium and morphine both increase serotonin levels. Use Caution/Monitor.
- lofepramine
morphine and lofepramine both increase sedation. Use Caution/Monitor.
lofepramine and morphine both increase serotonin levels. Modify Therapy/Monitor Closely. - lofexidine
morphine and lofexidine both increase sedation. Use Caution/Monitor.
lofexidine will decrease the level or effect of naltrexone by unknown mechanism. Modify Therapy/Monitor Closely. Coadministration of lofexidine with oral naltrexone resulted in statistically significant differences in the steady-state pharmacokinetics of naltrexone. The efficacy of oral naltrexone may be reduced if administered within 2 hours of taking lofexidine. Interaction not expected with other naltrexone routes of administration. - lonafarnib
lonafarnib will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.
- nabilone
naltrexone increases effects of nabilone by Other (see comment). Use Caution/Monitor. Comment: Naltrexone may enhance therapeutic effects of cannabinoids. .
Minor (10)
- benazepril
morphine, benazepril. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. May increase risk of hypotension.
- brimonidine
brimonidine increases effects of morphine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.
- celandine
celandine increases effects of morphine by unspecified interaction mechanism. Minor/Significance Unknown. Based on animal studies.
- dextroamphetamine
dextroamphetamine increases effects of morphine by unspecified interaction mechanism. Minor/Significance Unknown.
- eucalyptus
morphine and eucalyptus both increase sedation. Minor/Significance Unknown.
- lidocaine
lidocaine increases toxicity of morphine by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.
- rifabutin
rifabutin decreases levels of morphine by increasing metabolism. Minor/Significance Unknown.
- rifampin
rifampin decreases levels of morphine by increasing metabolism. Minor/Significance Unknown.
- sage
morphine and sage both increase sedation. Minor/Significance Unknown.
- ziconotide
ziconotide, morphine. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.
Adverse Effects
>10%
Somnolence
Constipation
Nausea
1-10% (selected)
Edema peripheral
Anxiety
Chills
Depression
Dizziness
Fatigue
Headache
Insomnia
Irritability
Lethargy
Restlessness
Sedation
Tremor
Hyperhidrosis
Pruritus
Hot flush
Abdominal pain
Anorexia
Dry mouth
Diarrhea
Dyspepsia
Decreased appetite
Flatulence
Stomach discomfort
Vomiting
Arthralgia
Muscle spasms
Frequency Not Defined
Cardiac arrest
Hypotension
Shock
Anaphylaxis
Apnea
Respiratory arrest
Respiratory depression
Opioid withdrawal
Warnings
Black Box Warnings
Opioid analgesic risk evaluation and mitigation strategy (REMS)
- To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products; under requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers
Healthcare providers are strongly encouraged to:
- Complete a REMS-compliant education program
- Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products
- Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist
- Consider other tools to improve patient, household, and community safety
Addiction, abuse, and misuse
- Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
- Assess each patient’s risk prior to prescribing and monitor all patients regularly for the development of these behaviors or conditions
Life-threatening respiratory depression
- Serious, life-threatening, or fatal respiratory depression may occur
- Monitor for respiratory depression, especially during initiation or following a dose increase
- Instruct patients to swallow tablet/capsule whole; crushing, chewing, or dissolving can cause rapid release and absorption of a potentially fatal morphine dose
Accidental exposure
- Accidental ingestion of even 1 dose, especially by children, can result in a fatal overdose
Neonatal opioid withdrawal syndrome
- Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts
- Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight
- Onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn
- If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Interaction with alcohol
- Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products that contain alcohol
- Coingestion of alcohol may cause rapid release of opioid content from long-acting tablet/capsule and result in increased plasma levels and a potentially fatal overdose
Central nervous system (CNS) depressants
- Coadministration with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death
- Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation
- Instruct patients not to consume alcoholic beverages or use alcohol-containing drug products while taking morphine due to risk of additive sedation and respiratory depression
Contraindications
Known hypersensitivity to morphine, morphine slats, naltrexone, or in any situation where opioids are contraindicated
Respiratory depression
Acute or severe asthma or hypercarbia
Gastrointestinal obstruction, including paralytic ileus
Cautions
Abuse-deterrent properties: Releases only the morphine in the capsule when swallowed whole; when crushed, the naltrexone blocks some of the euphoric effects of the morphine and can precipitate withdrawal in persons dependent on opioids
Pharmacologic effects vary widely; in addition to its therapeutic analgesic effect, may cause adverse effects including dysphoria, euphoria, somnolence, respiratory depression, diminished gastrointestinal motility, altered circulatory dynamics, histamine release, physical dependence, & alterations of the endocrine and autonomic nervous systems
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia; opioid use increases risk of CSA in a dose-dependent fashion; in patients who present with CSA, consider decreasing opioid dosage using best practices for opioid taper
Cases of serotonin syndrome, a potentially life-threatening condition, reported with concomitant use of serotonergic drugs; this may occur within the recommended dosage range; the onset of symptoms generally occur within several hours to a few days of concomitant use, but may occur later than that; discontinue therapy immediately if serotonin syndrome is suspected
Therapy may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients; there is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics); monitor patients for signs of hypotension after initiating or titrating dosage; in patients with circulatory shock, therapy may cause vasodilation that can further reduce cardiac output and blood pressure; avoid therapy in patients with circulatory shock
In patients who may be susceptible to intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory drive, and resultant CO2 retention can further increase intracranial pressure; monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy; opioids may obscure clinical course in a patient with a head injury; avoid the use in patients with impaired consciousness or coma
Contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus; may cause spasm of sphincter of Oddi; opioids may cause increases in serum amylase; monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms
Therapy may increase frequency of seizures in patients with seizure disorders and in other clinical settings associated with seizures; monitor patients for worsened seizure control during therapy
Avoid use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic; mixed agonist/antagonist and partial agonist analgesics may reduce analgesic effect and/or precipitate withdrawal symptoms; when discontinuing therapy in physically-dependent patient, gradually taper dosage; do not abruptly discontinue therapy in these patients
Warn patients not to drive or operate dangerous machinery unless they are tolerant to effects of drug and know how they will react to medication
While serious, life-threatening, or fatal respiratory depression can occur at any time during therapy, risk is greatest during initiation of therapy or following dosage increase; monitor patients closely for respiratory depression, especially within first 24 to 72 hr of initiating therapy with and following dosage increases; accidental ingestion of even one dose, especially by children, can result in respiratory depression and death due to overdose of opioid
Monoamine oxidase inhibitors (MAOIs) may potentiate effects of opioid, opioid’s active metabolite, including respiratory depression, coma, and confusion; therapy should not be administered within 14 days of initiating or stopping MAOIs
Not indicated for acute/postoperative pain, mild pain, or short-term pain relief; only indicated for postoperative use if patient already receiving chronic opioid therapy prior to surgery, or if postoperative pain is expected to be moderate-to-severe and persist for an extended period of time
Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there is a greater risk for overdose and death with extended-release opioids due to the larger amount of active opioid present (see Black Box Warnings)
Addiction, abuse, and misuse risks are increased in patients with a personal or family history of substance abuse or mental illness (eg, major depression); the potential for these risks should not, however, prevent the prescribing of proper pain management in any given patient; intensive monitoring is necessary (see Black Box Warnings)
Accidental exposure reported, including fatalities (see Black Box Warnings)
Do not abruptly discontinue therapy in a patient physically dependent on opioids; when discontinuing therapy, in a physically dependent patient, gradually taper the dosage; rapid tapering in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain
Neonatal opioid withdrawal syndrome reported with long-term use during pregnancy (see Black Box Warnings)
Opioid pharmacokinetics may be altered in patients with renal failure; clearance may be decreased and metabolites may accumulate much higher plasma levels in patients with renal failure as compared to patients with normal renal function; start with a lower than normal dosage or with longer dosing intervals and titrate slowly while monitoring for signs of respiratory depression, sedation, and hypotension
Profound sedation, respiratory depression, coma, and death may result from concomitant administration with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol); because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate; must not consume alcohol while taking morphine/naloxone
If the decision to begin morphine/naloxone is made, start with 20 mg/0.8 mg q24hr, monitor patients for signs of sedation and respiratory depression, and consider using a lower dose of the concomitant CNS depressant
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients
Use caution when selecting dosage for an elderly patient, usually starting at low end of dosing range, reflecting greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy; because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and may be useful to monitor renal function
Opioid analgesic risk evaluation and mitigation strategy (REMS)
- To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products
- Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed; use the following link to obtain the Patient Counseling Guide (PCG): www.fda.gov/OpioidAnalgesicREMSPCG
- Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them
- Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient-prescriber responsibilities
- To obtain further information on opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint
Pregnancy & Lactation
Pregnancy
Prolonged use of opioid analgesics during pregnancy can cause neonatal opioid withdrawal syndrome; there are no available data in pregnant women to inform a drug associated risk for major birth defects and miscarriage; published studies with morphine use during pregnancy have not reported a clear association with morphine and major birth defects
Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; the onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of drug by newborn; observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly
Labor and delivery
- Opioids cross placenta and may produce respiratory depression and psycho-physiologic effects in neonates; an opioid antagonist, such as naloxone, must be available for reversal of opioid induced respiratory depression in neonate; drug is not recommended for use in women during and immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate; opioid analgesics can prolong labor through actions that temporarily reduce strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor; monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression
Infertility
- Due to effects of androgen deficiency, chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether effects on fertility are reversible
Lactation
Morphine is present in breast milk; published lactation studies report variable concentrations of morphine in breast milk with administration of immediate-release morphine to nursing mothers in the early postpartum period with a milk-to-plasma morphine AUC ratio of 2.5:1 measured in one lactation study; however, there is insufficient information to determine effects of morphine on breastfed infant and effects of morphine on milk production; no information is available on effects of drug on breastfed infant or effects of drug on milk production
The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition
Monitor infants exposed to therapy through breast milk for excess sedation and respiratory depression; withdrawal symptoms can occur in breastfed infants when maternal administration of morphine is stopped, or when breastfeeding is stopped
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Morphine is a pure opioid agonist, relatively selective for the mu-opioid receptor; inhibits ascending pain pathways, which causes alteration in response to pain; produces analgesia, respiratory depression, and sedation
Naltrexone is a centrally acting mu-opioid antagonist; only becomes active and antagonizes opioid agonsists when the tablet is either chewed, crushed, or dissolved
Pharmacokinetics
Pharmacokinetic parameters are for morphine unless otherwise stated
Bioavailability: 20-40%
Peak Plasma Time: 7.5 hr
Protein Binding: 30-35%
Half-Life: 29 hr
Volume of distribution: 3-4 L/kg
Metabolism: Glucuronidation and sulfation in the liver to produce including morphine-3-glucuronide, M3G (about 50%) and morphine-6-glucuronide, M6G (about 5 to 15%) or morphine-3-etheral sulfate; naltrexone extensively metabolized to 6-beta-naltrexol
Clearance: 20-30 mL/min/kg
Excretion: Morphine: 10% excreted unchanged in urine, 55-65 metabolites excreted in urine
