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Drug Interactions between amprenavir and ombitasvir / paritaprevir / ritonavir

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

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Interactions between your drugs

Moderate

ritonavir amprenavir

Applies to: ombitasvir / paritaprevir / ritonavir and amprenavir

ADJUST DOSE: The concomitant administration of ritonavir may significantly increase amprenavir AUC and trough concentrations. In healthy subjects, amprenavir AUC increased by 62% to 64% and trough concentrations increased by 319% to 508% with ritonavir 200 mg/day. The mechanism is inhibition of CYP450 3A4 metabolism by ritonavir.

MANAGEMENT: The manufacturer recommends that the adult amprenavir dosage be reduced to 1200 mg once daily with ritonavir 200 mg once daily or 600 mg twice daily with ritonavir 100 mg twice daily.

References

  1. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome PROD (2001):

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Moderate

amprenavir paritaprevir

Applies to: amprenavir and ombitasvir / paritaprevir / ritonavir

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of paritaprevir, which is primarily metabolized by the isoenzyme. In 12 study subjects, ketoconazole 400 mg given once daily increased single-dose paritaprevir peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 37% and 98%, respectively. The risk of hyperbilirubinemia may be increased, as paritaprevir can cause elevations in indirect (unconjugated) bilirubin via inhibition of OATP1B1/1B3.

MANAGEMENT: Caution is advised if paritaprevir is prescribed in combination with potent CYP450 3A4 inhibitors. Patients should be monitored for signs and symptoms of hepatotoxicity (i.e., ALT and bilirubin elevations).

References

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

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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. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

amprenavir food

Applies to: amprenavir

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.

References

  1. "Product Information. Agenerase (amprenavir)." Glaxo Wellcome PROD (2001):
  2. Demarles D, Gillotin C, Bonaventure-Paci S, Vincent I, Fosse S, Taburet AM "Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice." Antimicrob Agents Chemother 46 (2002): 1589-1590

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

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Protease inhibitors

Therapeutic duplication

The recommended maximum number of medicines in the 'protease inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'protease inhibitors' category:

  • amprenavir
  • ombitasvir/paritaprevir/ritonavir

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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.