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Drug Interactions between Inlyta and ombitasvir / paritaprevir / ritonavir

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

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Interactions between your drugs

Major

ritonavir axitinib

Applies to: ombitasvir / paritaprevir / ritonavir and Inlyta (axitinib)

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of axitinib, which is primarily metabolized by the isoenzyme. In 32 healthy volunteers, administration of a single 5 mg dose of axitinib on day 4 of treatment with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 7 days) resulted in a 1.5-fold increase in mean axitinib peak plasma concentration (Cmax) and 2-fold increase in mean systemic exposure (AUC) compared to administration of axitinib alone. The mean plasma half-life of axitinib also increased from 9.4 hours when given alone to 13.1 hours in the presence of ketoconazole. The combination was well tolerated by study subjects. Most treatment-related adverse events were mild in severity, with headache and nausea reported most frequently. No clinically significant effects on blood pressure were observed for single-dose axitinib plus ketoconazole relative to axitinib alone.

MANAGEMENT: Concomitant use of axitinib with potent CYP450 3A4 inhibitors should generally be avoided. Some authorities recommend avoiding concomitant use of axitinib during and for 2 weeks after treatment with itraconazole. Alternative agents with no or minimal CYP450 3A4 inhibition potential are recommended whenever possible. Should concomitant treatment with a potent inhibitor be required, the manufacturer recommends that axitinib dosage be reduced by approximately one-half, as this is predicted to adjust the axitinib systemic exposure (AUC) to the range observed without inhibitors; however, clinical data are lacking. Subsequent dosage adjustments can be made according to individual therapeutic response and tolerability. Following discontinuation of the potent CYP450 3A4 inhibitor, the axitinib dosage should be returned (after 3 to 5 half-lives of the inhibitor) to that used prior to initiation of the inhibitor.

References

  1. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2012) "Product Information. Inlyta (axitinib)." Pfizer U.S. Pharmaceuticals Group
View all 4 references

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Drug and food interactions

Moderate

ritonavir food

Applies to: ombitasvir / paritaprevir / 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. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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Moderate

axitinib food

Applies to: Inlyta (axitinib)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of axitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients treated with axitinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Axitinib may be administered with or without food.

References

  1. (2012) "Product Information. Inlyta (axitinib)." Pfizer U.S. Pharmaceuticals Group

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Moderate

paritaprevir food

Applies to: ombitasvir / paritaprevir / ritonavir

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of ombitasvir, paritaprevir, ritonavir, and dasabuvir. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a moderate-fat meal (approximately 600 Kcal; 20% to 30% calories from fat) increased the mean systemic exposure (AUC) by 82%, 211%, 49%, and 30%, respectively. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a high-fat meal (approximately 900 Kcal; with 60% calories from fat) increased the mean AUC by 76%, 180%, 44%, and 22%, respectively.

MANAGEMENT: Ombitasvir/paritaprevir/ritonavir plus dasabuvir should always be administered with a meal. The fat or calorie content does not matter.

References

  1. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC

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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.

See also

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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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