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Drug Interactions between Paxlovid and propoxyphene

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

propoxyphene ritonavir

Applies to: propoxyphene and Paxlovid (nirmatrelvir / ritonavir)

CONTRAINDICATED: Coadministration with ritonavir may increase the plasma concentrations of propoxyphene. The proposed mechanism is inhibition of the CYP450 2D6-mediated metabolism of propoxyphene by ritonavir. Clinical data have not been reported; however, the accumulation of propoxyphene may result in excessive central nervous system (CNS)- and/or respiratory-depressant effects. Excessive doses of propoxyphene, either alone or in combination with other CNS depressants, have been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, and/or drug or alcohol abuse. In a large Canadian study, propoxyphene use was also associated with a 60% increased risk of hip fracture in the elderly.

MANAGEMENT: Concomitant use of propoxyphene is considered contraindicated by the manufacturers of some ritonavir-containing products. If coadministration is required, caution and dosage reductions of propoxyphene are recommended.

References (3)
  1. EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
  2. Cerner Multum, Inc. "Australian Product Information."
  3. US Food and Drug Administration (2021) FACT SHEET FOR HEALTHCARE PROVIDERS EMERGENCY USE AUTHORIZATION FOR PAXLOVID. https://www.fda.gov/media/155050/download
Major

propoxyphene nirmatrelvir

Applies to: propoxyphene and Paxlovid (nirmatrelvir / ritonavir)

CONTRAINDICATED: Coadministration of ritonavir-boosted nirmatrelvir may lead to increased effects of propoxyphene. Ritonavir inhibits CYP450 isoenzymes and may interfere with the metabolism of propoxyphene. Clinical data have not been reported; however, the accumulation of propoxyphene may result in excessive CNS- and/or respiratory-depressant effects. Excessive doses of propoxyphene, either alone or in combination with other CNS depressants, have been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse. In a large Canadian study, propoxyphene use was also associated with a 60% increased risk of hip fracture in the elderly.

MANAGEMENT: The manufacturer of nirmatrelvir-ritonavir considers concomitant use with propoxyphene to be contraindicated.

References (2)
  1. EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
  2. US Food and Drug Administration (2021) FACT SHEET FOR HEALTHCARE PROVIDERS EMERGENCY USE AUTHORIZATION FOR PAXLOVID. https://www.fda.gov/media/155050/download

Drug and food interactions

Major

propoxyphene food

Applies to: propoxyphene

GENERALLY AVOID: Alcohol may have additive CNS- and/or respiratory-depressant effects with propoxyphene. Misuse of propoxyphene, either alone or in combination with other CNS depressants, has been a major cause of drug-related deaths, particularly in patients with a history of emotional disturbances, suicidal ideation, or alcohol and drug abuse.

MANAGEMENT: The use of alcohol during propoxyphene therapy should be avoided. Patients should be warned not to exceed the recommended dosage of propoxyphene and to avoid activities requiring mental alertness until they know how these agents affect them.

References (1)
  1. (2001) "Product Information. Darvon (propoxyphene)." Lilly, Eli and Company
Moderate

ritonavir food

Applies to: Paxlovid (nirmatrelvir / ritonavir)

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References (1)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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