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Drug Interactions between Krazati and maraviroc

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

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Interactions between your drugs

Major

maraviroc adagrasib

Applies to: maraviroc and Krazati (adagrasib)

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of maraviroc, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of maraviroc (100 mg twice a day) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once a day) increased the mean maraviroc peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 3.5- and 5-fold, respectively, compared to administration alone. When the same dosage of maraviroc was administered with ritonavir (100 mg twice a day), maraviroc Cmax increased by nearly 1.3-fold and AUC by 2.6-fold. An even greater increase of nearly 5-fold in Cmax and 10-fold in AUC was observed during coadministration of maraviroc and saquinavir/ritonavir (1000 mg/100 mg twice a day). At 300 mg twice a day, mean maraviroc Cmax increased by approximately 2-fold and AUC by 3.6-fold during coadministration with atazanavir (400 mg once a day). When the same dosage of maraviroc was given with atazanavir/ritonavir (300 mg/100 mg once a day), maraviroc Cmax increased by 2.7-fold and AUC increased by nearly 5-fold. During coadministration with lopinavir/ritonavir (400 mg/100 mg twice a day), maraviroc Cmax and AUC increased by 2-fold and 4-fold, respectively. In patients with hepatic impairment, plasma drug concentrations are higher when maraviroc 150 mg is administered with a potent CYP450 3A4 inhibitor than when maraviroc 300 mg (normally recommended dose) is administered without a CYP450 3A4 inhibitor.

CONTRAINDICATED: Patients with severe renal impairment or end-stage renal disease (CrCl <30 mL/min) given maraviroc in combination with potent CYP450 3A4 inhibitors may have an increased risk of postural hypotension due to increased maraviroc exposure. Moreover, these patients often have cardiovascular comorbidities that could predispose them to adverse cardiovascular events triggered by postural hypotension. No studies have been performed in subjects with severe renal impairment or ESRD co-treated with maraviroc and potent CYP450 3A4 inhibitors. Hence, no dosage recommendation for maraviroc is available for these patients.

MANAGEMENT: Maraviroc should be administered at a dosage of 150 mg twice daily during coadministration with potent CYP450 3A4 inhibitors, including most protease inhibitors except tipranavir plus ritonavir. This dosage is recommended whether or not a concomitant CYP450 3A4 inducer (e.g., efavirenz, rifampin, carbamazepine, phenobarbital, phenytoin) is given. Patients with moderate hepatic impairment who receive 150 mg with a potent CYP450 3A4 inhibitor should be monitored closely for maraviroc-associated adverse events. Maraviroc is contraindicated for use in combination with potent CYP450 3A4 inhibitors in patients with severe renal impairment or end-stage renal disease (CrCl <30 mL/min).

References (1)
  1. (2007) "Product Information. Selzentry (maraviroc)." Pfizer U.S. Pharmaceuticals Group

Drug and food interactions

Major

adagrasib food

Applies to: Krazati (adagrasib)

ADJUST DOSING INTERVAL: Adagrasib can cause concentration-dependent, prolongation of the QT interval. Theoretically, coadministration with grapefruit juice before adagrasib has reached steady-state may significantly increase the plasma concentrations of adagrasib, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for the potent CYP450 3A4 inhibitor, itraconazole. In a clinical drug interaction study, adagrasib peak plasma concentration (Cmax) and systemic exposure (AUC) were increased by 2.4-fold and 4-fold, respectively following concomitant use of a single dose of adagrasib (200 mg) with itraconazole. No clinically significant differences in the pharmacokinetics of adagrasib at steady state were predicted when used concomitantly with itraconazole. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to adagrasib may increase the risk of adverse effects such as QT prolongation, diarrhea, fatigue, musculoskeletal pain, hepatotoxicity, and renal impairment.

Adagrasib pharmacokinetics were not significantly affected when administered with a high-fat meal.

MANAGEMENT: Although clinical data are lacking, it may be advisable to avoid the consumption of grapefruit or grapefruit juice until adagrasib concentrations have reached steady state (after approximately 8 days). Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Adagrasib may be administered with or without food.

References (1)
  1. (2022) "Product Information. Krazati (adagrasib)." Mirati Therapeutics, Inc.
Minor

maraviroc food

Applies to: maraviroc

Administration with food may reduce the bioavailability of maraviroc. According to the product labeling, coadministration of a 300 mg dose of maraviroc with a high-fat breakfast reduced maraviroc peak plasma concentration (Cmax) and systemic exposure (AUC) by 33% in healthy volunteers. However, no food restrictions were used in the clinical studies that demonstrated the safety and efficacy of maraviroc. Therefore, maraviroc can be taken with or without food at the recommended dosage.

References (1)
  1. (2007) "Product Information. Selzentry (maraviroc)." Pfizer U.S. Pharmaceuticals Group

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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