Morphine with Cimetidine Interaction Details

Brand Names Associated with Morphine

Brand Names Associated with Cimetidine

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 20, 2023

Interaction Effect

Morphine toxicity (CNS depression, respiratory depression)

Interaction Summary

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 ratio. However, a crossover study showed no effect on morphine pharmacokinetics by cimetidine administration, suggesting that cimetidine had no significant effect on hepatic blood flow . In addition, another study using ventilatory response showed only a small, clinically insignificant effect on morphine's respiratory effects by concurrent cimetidine administration . In contrast, one hemodialysis patient experienced morphine toxicity when given both drugs concurrently .

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Carefully monitor the patient for morphine toxicity (eg, CNS and respiratory depression). If an interaction is suspected with the concurrent or sequential use of cimetidine, carefully titrate the morphine dose until an adequate clinical response is observed.

Mechanism Of Interaction

Unknown; possibly decreased metabolism

Literature Reports

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 .

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 .

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.

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.

Morphine Overview

• Morphine is used to relieve moderate to severe pain. Morphine extended-release tablets and capsules are only used to relieve severe (around-the-clock) pain that cannot be controlled by the use of other pain medications. Morphine extended-release tablets and capsules should not be used to treat pain that can be controlled by medication that is taken as needed. Morphine is in a class of medications called opiate (narcotic) analgesics. It works by changing the way the brain and nervous system respond to pain.

Cimetidine Overview

• Cimetidine is used to treat ulcers; gastroesophageal reflux disease (GERD), a condition in which backward flow of acid from the stomach causes heartburn and injury of the food pipe (esophagus); and conditions where the stomach produces too much acid, such as Zollinger-Ellison syndrome. Over-the-counter cimetidine is used to prevent and treat symptoms of heartburn associated with acid indigestion and sour stomach. Cimetidine is in a class of medications called H₂ blockers. It decreases the amount of acid made in the stomach.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.