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Drug Interactions between pirfenidone and vemurafenib

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

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Interactions between your drugs

Major

vemurafenib pirfenidone

Applies to: vemurafenib and pirfenidone

GENERALLY AVOID: Coadministration with moderate or potent inhibitors of CYP450 1A2 may significantly increase the plasma concentrations of pirfenidone, which is primarily (70% to 80%) metabolized by the isoenzyme. Other CYP450 isoenzymes also contribute to a minor extent, including CYP450 2C9, 2C19, 2D6, and 2E1. Concomitant inhibition of one or more of these isoenzymes in addition to CYP450 1A2 is expected to further increase the magnitude of interaction. In 27 healthy study subjects, administration of a single 801 mg dose of pirfenidone on day 6 of treatment with the moderate CYP450 1A2 inhibitor ciprofloxacin (750 mg twice daily) increased pirfenidone peak plasma concentration (Cmax) and systemic exposure (AUC) by 23% and 81%, respectively. In 25 healthy nonsmokers and 25 smokers who were administered a single dose of pirfenidone with the potent CYP450 1A2 inhibitor fluvoxamine (50 mg at bedtime for 3 days; 50 mg twice a day for 3 days; then 50 mg in the morning and 100 mg at bedtime for 4 days), pirfenidone AUC increased approximately 4-fold in nonsmoking subjects and 7-fold in smoking subjects. Fluvoxamine also inhibits CYP450 2C9, 2C19 and 2D6, although the extent to which these effects contribute to the interaction has not been established.

MANAGEMENT: Concomitant use of pirfenidone with a drug or combination of drugs that may produce moderate or potent inhibition of both CYP450 1A2 and one or more other CYP450 isoenzymes involved in the metabolism of pirfenidone (i.e., CYP450 2C9, 2C19, 2D6, and 2E1) should generally be avoided. These drugs should be discontinued prior to the initiation of pirfenidone and avoided during therapy. If concomitant use cannot be avoided, patients should be closely monitored for adverse reactions such as hepatotoxicity, photosensitivity, rash, nausea, diarrhea, vomiting and dyspepsia, and consideration be given to brief interruption or permanent discontinuation of pirfenidone if clinically necessary in accordance with the product labeling.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2013) "Product Information. Esbriet (pirfenidone)." Intermune Inc

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Drug and food interactions

Moderate

pirfenidone food

Applies to: pirfenidone

ADJUST DOSING INTERVAL: Food significantly slows the rate but only modestly reduces the extent of absorption of pirfenidone. In healthy, older adult volunteers aged 50 to 66 years, administration of a single 801 mg oral dose of pirfenidone in the fed state resulted in an approximately 50% reduction in peak plasma concentration (Cmax) and a 15% to 20% reduction in systemic exposure (AUC) compared to administration in the fasted state. Median time to reach peak concentration (Tmax) increased from 0.5 hours to 3 hours with food. Less nausea and dizziness were observed in fed subjects compared to fasted subjects.

GENERALLY AVOID: Consumption of grapefruit juice is associated with inhibition of CYP450 1A2 and may increase the plasma concentrations of pirfenidone, which is primarily metabolized by the isoenzyme.

GENERALLY AVOID: Cigarette smoking may reduce pirfenidone exposure due to induction of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of pirfenidone. Following a single 801 mg oral dose of pirfenidone in 25 smokers and 25 healthy nonsmokers, the Cmax and AUC of pirfenidone in smokers were 68% and 46% of those in nonsmokers, respectively.

MANAGEMENT: Pirfenidone should be administered with food to reduce the likelihood of dizziness and gastrointestinal side effects such as nausea, diarrhea, dyspepsia, and vomiting. Patients who experience intolerance to therapy due to these adverse events should be reminded to take pirfenidone with food. If symptoms do not improve, or they worsen in severity, a dosage reduction or discontinuation of therapy may be warranted. Patients should be advised to avoid consumption of grapefruit and grapefruit juice during treatment with pirfenidone. Cigarette smoking should also be avoided during therapy to prevent reduced exposure to pirfenidone.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Esbriet (pirfenidone)." Intermune Inc

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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