Skip to main content

Drug Interactions between pirfenidone and quinidine

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

quiNIDine pirfenidone

Applies to: quinidine and pirfenidone

MONITOR: Coadministration with moderate or potent inhibitors of CYP450 2C9, 2C19, 2D6, and/or 2E1 may increase the plasma concentrations of pirfenidone, especially when used in addition to a moderate or potent CYP450 1A2 inhibitor. Pirfenidone is primarily (70% to 80%) metabolized by CYP450 1A2, with minor contribution from CYP450 2C9, 2C19, 2D6, and 2E1. 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 systemic exposure (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. The interaction has not been studied with specific inhibitors of other isoenzymes involved in the metabolism of pirfenidone.

MANAGEMENT: Concomitant use of pirfenidone with moderate or potent inhibitors of CYP450 2C9, 2C19, 2D6, and/or 2E1 in addition to a moderate or potent inhibitor of CYP450 1A2 (e.g., certain fluoroquinolones, oral contraceptives, deferasirox, methoxsalen, mexiletine, thiabendazole, ticlopidine, zileuton) should be avoided. No particular precaution is necessary if pirfenidone and CYP450 2C9, 2C19, 2D6, and/or 2E1 inhibitors are coadministered without a moderate or potent CYP450 1A2 inhibitor. However, a prolonged duration of monitoring for adverse effects may be required depending on the elimination half-life of the concomitant drug. For example, it should be noted that rolapitant, a moderate CYP450 2D6 inhibitor, may increase plasma concentrations and the risk of adverse effects of pirfenidone for at least 28 days after administration of rolapitant.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2013) "Product Information. Esbriet (pirfenidone)." Intermune Inc
  3. (2015) "Product Information. Varubi (rolapitant)." Tesaro Inc.

Switch to consumer interaction data

Drug and food interactions

Moderate

quiNIDine food

Applies to: quinidine

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL (1983) "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos, 4, p. 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F (1995) "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol, 48, p. 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
View all 4 references

Switch to consumer interaction data

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

Switch to consumer interaction data

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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer