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Drug Interactions between Plavix and rifampin

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

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Interactions between your drugs

Moderate

rifAMPin clopidogrel

Applies to: rifampin and Plavix (clopidogrel)

GENERALLY AVOID: Coadministration with potent inducers of CYP450 2C19 may enhance the metabolic activation of clopidogrel, resulting in increased platelet inhibition and possibly bleeding risk. Clopidogrel is a prodrug that is converted to its active metabolite (AM) primarily by CYP450 2C19, with contributions from several other CYP450 isoenzymes including CYP450 3A, 2B6, and 1A2. When clopidogrel (600 mg loading dose followed by 75 mg once daily for 7 days) was coadministered with the potent CYP450 2C19 and 3A4 inducer rifampin (300 mg twice daily for 14 days) in twelve healthy volunteers, mean clopidogrel AM peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 3.8-fold. Mean inhibition of platelet aggregation at 4 hours post loading dose was 34% higher in the presence of rifampin compared to clopidogrel administered alone. When clopidogrel (75 mg once daily for 6 days) was coadministered with rifampin (300 mg twice daily for 10 days) in another study of ten healthy volunteers, platelet aggregation was 33% as compared to 56% following clopidogrel alone for 6 days and 94% at baseline.

MANAGEMENT: Concomitant use of clopidogrel with potent CYP450 2C19 inducers should be avoided when possible. If coadministration is required, patients should be monitored closely for signs of bleeding.

References

  1. Lau WC, Waskell LA, Watkins PB, et al. (2003) "Atorvastatin reduces the ability of clopidogrel to inhibit platelet aggregation: a new drug-drug interaction." Circulation, 107, p. 32-7
  2. Lau WC, Gurbel PA, Watkins PB, et al. (2004) "Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance." Circulation, 109, p. 166-71
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
  5. Judge HM, Patil SB, Buckland RJ, Jakubowski JA, Storey RF (2010) "Potentiation of clopidogrel active metabolite formation by rifampicin leads to greater P2Y12 receptor blockade and inhibition of platelet aggregation after clopidogrel." J Thromb Haemost, 8, p. 1820-7
View all 5 references

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Drug and food interactions

Moderate

rifAMPin food

Applies to: rifampin

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.

References

  1. (2022) "Product Information. Rifampin (rifAMPin)." Akorn Inc
  2. (2022) "Product Information. Rifampicin (rifampicin)." Mylan Pharmaceuticals Inc
  3. (2023) "Product Information. Rifadin (rifampicin)." Sanofi
  4. (2024) "Product Information. Rifadin (rifaMPICin)." Sanofi-Aventis Australia Pty Ltd
  5. Peloquin CA, Namdar R, Singleton MD, Nix DE (2024) Pharmacokinetics of rifampin under fasting conditions, with food, and with antacids https://pubmed.ncbi.nlm.nih.gov/9925057/
  6. (2019) "Product Information. Rofact (rifampin)." Bausch Health, Canada Inc.
View all 6 references

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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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