Rifampin and Morphine Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Rifampin
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 or reduced morphine exposure and an increased risk of morphine-related adverse effects (hypotension, respiratory depression, profound sedation, coma)
Interaction Deep Dive
Concomitant use of morphine and rifAMPin (P-gp inhibitor) may reduce morphine exposure456. Additionally, coadministration may increase the exposure of morphine by two-fold and increase the risk of adverse effects, including respiratory and CNS depression. If coadministration is required, monitor for signs of CNS depression. Evaluate patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of morphine and/or rifAMPin as necessary 132.
Why it happens (mechanism)
Inhibition of P-gp-mediated efflux transport of rifAMPin; unknown
Literature reports
1 report — tap to read
a) Ten healthy male volunteers participated in a double-blind, placebo-controlled study with a double crossover design to evaluate the effects of rifAMPin administration on the pharmacokinetics and analgesic properties of morphine. Oral morphine 10 mg or matching placebo were given on two separate occasions before and near the end of pretreatment with rifAMPin 600 mg daily. The area under the concentration-time curve (AUC) and maximum concentration (Cmax) of morphine were reduced from 132 pmol/h/mL to 97 pmol/h/mL and from 34.5 pmol/mL to 18.9 pmol/mL, respectively, during rifAMPin treatment. Analgesic effect was determined by the cold pressor test apparatus which consisted of an ice-water bath. The time interval from immersion of the forearm into the water bath to the first pain sensation was defined as the pain threshold, and the time interval from immersion to the point of intolerable pain was labeled the pain tolerance. Both the pain threshold and pain tolerance were significantly decreased when rifAMPin was coadministered with morphine when compared to morphine monotherapy and were similar to the values seen when placebo was administered 7.
Common questions
Can I take Rifampin and Morphine Injection together?
Increased or reduced morphine exposure and an increased risk of morphine-related adverse effects (hypotension, respiratory depression, profound sedation, coma) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Rifampin 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 "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Rifampin 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 (7)
- 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: RIFADIN(R) IV intravenous injection, rifampin intravenous injection. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Product Information: RIFADIN(R) oral capsules, rifampin oral capsules. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Product Information: RIFATER(R) oral tablets, rifampin, isoniazid, pyrazinamide oral tablets. sanofi-aventis US LLC (per FDA), Bridgewater, NJ, 2023. DailyMed
- Fromm MF, Eckhardt K, Li S, et al: Loss of analgesic effect of morphine due to coadministration of rifampin. Pain 1997; 72:261-267. PubMed
Keep reading about Rifampin
Keep reading about Morphine Injection
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