Cimetidine and Morphine Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cimetidine
Morphine Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased risk of apnea, confusion and muscle twitching, an increased morphine exposure and an increased risk of morphine toxicity ((hypotension, respiratory depression, profound sedation, coma and respiratory depression)
Interaction Deep Dive
Morphine is metabolized primarily via glucuronidation pathways which would not be expected to be altered by cimetidine inhibition of the cytochrome systems. Morphine metabolism might be expected to be inhibited by a possible reduction in hepatic blood flow caused by cimetidine because morphine has a high hepatic extraction ratio10. The concomitant use of morphine and cimetidine has been reported to precipitate apnea, confusion, and muscle twitching 4. The concomitant use of cimetidine (P-gp inhibitor) can increase the exposure to morphine by two-fold and can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Evaluate patients for increased CNS depression. Also, evaluate patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of morphine and/or cimetidine as necessary 321.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of cimetidine
Literature reports
5 reports — tap to read
a) The pharmacokinetics of morphine was studied in a crossover design following four days pretreatment with 300 mg cimetidine every six hours or placebo. There was no demonstrable effect on morphine's clearance, AUC, or half-life 5.
b) Ventilatory response to added carbon dioxide was studied in eight healthy patients receiving cimetidine and morphine. The respiratory depression was greater when cimetidine was given with morphine than when morphine was given alone, but the magnitude of the interaction was small and not clinically significant in healthy subjects 6.
c) A 46-year-old, long term hemodialysis patient experienced two episodes of apnea, confusion, and seizure during morphine administration. The first episode occurred with the sixth dose of intramuscular morphine 15 mg every four hours after the patient had been receiving cimetidine 300 mg three times daily. The second episode occurred when cimetidine 150 mg twice daily and intramuscular Pantopon (15 mg total opium alkaloids) every three to six hours were started post-operatively 7.
d) The clearance of meperidine was reduced 22% when it was used with cimetidine, but not with ranitidine A cimetidine-induced reduction in meperidine oxidation was indicated by a 23% reduction in the AUC of normeperidine 89.
e) The concomitant use of morphine and cimetidine has been reported to precipitate apnea, confusion, and muscle twitching in an isolated report 4.
Common questions
Can I take Cimetidine and Morphine Injection together?
Increased risk of apnea, confusion and muscle twitching, an increased morphine exposure and an increased risk of morphine toxicity ((hypotension, respiratory depression, profound sedation, coma and respiratory depression) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Cimetidine and Morphine Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Cimetidine or Morphine Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (10)
- Product Information: MS CONTIN(R) oral extended-release tablets, morphine sulfate oral extended-release tablets. Purdue Pharma LP (per FDA), Stamford, CT, 2023. DailyMed
- Product Information: Morphine sulfate oral tablets, morphine sulfate oral tablets. Hikma Pharmaceuticals USA Inc.(Per FDA), Berkeley, NJ, 2023. DailyMed
- Product Information: Morphine sulfate oral solution, morphine sulfate oral solution. Hikma Pharmaceuticals USA Inc (per FDA), Berkeley Heights, NJ, 2023. DailyMed
- Product Information: Morphine sulfate intravenous injection, morphine sulfate intravenous injection. Mallinckrodt Inc (Per FDA), St. Louis, MO, 2023. DailyMed
- Mojaverian P, Fedder IL, Vlasses PH, et al: Cimetidine does not alter morphine disposition in man. Br J Clin Pharmacol 1982; 14:809-813. DOI
- Lam AM & Clement JL: Effect of cimetidine premedication on morphine-induced ventilatory depression. Can Anaesth Soc J 1984; 31:36-43. PubMed
- Fine A & Churchill DN: Potentially lethal interaction of cimetidine and morphine (letter). Can Med Assoc J 1981; 124:1434-1436.
- Guay DRP, Meatherall RC, Chalmers JL, et al: Cimetidine alters pethidine disposition in man. Br J Clin Pharmacol 1984; 18:907-914. DOI
- Guay DR, Meatherall RC, Chalmers JL, et al: Ranitidine does not alter pethidine disposition in man. Br J Clin Pharmacol 1985; 20:55-59. PubMed
- Sorkin EM & Darvey DL: Review of cimetidine drug interactions. Drug Intell Clin Pharm 1983; 17:110-120. DOI
Keep reading about Cimetidine
Keep reading about Morphine Injection
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