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Drug Interactions between dasabuvir / ombitasvir / paritaprevir / ritonavir and Lariam

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

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Interactions between your drugs

Minor

mefloquine ritonavir

Applies to: Lariam (mefloquine) and dasabuvir / ombitasvir / paritaprevir / ritonavir

The coadministration with mefloquine may decrease the steady-state, but not single-dose, plasma concentrations of ritonavir. The mechanism is unknown but may be due to reduction of bile production by mefloquine, which may interfere with the solubility and absorption of ritonavir in the small intestine. In a study consisting of 12 healthy volunteers, mefloquine (250 mg orally once daily for 3 days, then once weekly for 4 weeks) decreased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of ritonavir (200 mg orally twice daily for 7 days) by 36% and 31%, respectively. The clearance increased by an average of 45% with no change in half-life or plasma protein binding. However, not all subjects had decreased ritonavir concentrations. Also, in a separate phase of the study involving 11 volunteers (8 of whom participated in the first phase), single-dose pharmacokinetics of ritonavir were not altered by mefloquine. Thus, the effects of the interaction, if it exists, may be inconsistent and subject to interpatient variability. Ritonavir had minimal effect on the pharmacokinetics of mefloquine and its carboxylic acid metabolite, despite strong inhibition of CYP450 3A4 activity as demonstated by the erythromycin breath test. Further studies are necessary to confirm or disprove the interaction.

References

  1. Khaliq Y, Gallicano K, Tisdale C, Carignan, Cooper C, McCarthy A "Pharmacokinetic interaction between mefloquine and ritonavir in healthy volunteers." Br J Clin Pharmacol 51 (2001): 591-600

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Drug and food interactions

Moderate

mefloquine food

Applies to: Lariam (mefloquine)

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of mefloquine. The proposed mechanism is increased drug solubility in the presence of food. In 20 healthy volunteers, administration of a single 750 mg oral dose of mefloquine 30 minutes following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of mefloquine by 73% and 40%, respectively, compared to administration in the fasting state. The Cmax and AUC of the carboxylic acid metabolite were also increased by 35% and 33%, respectively, compared to fasting. In addition, the time to reach peak plasma concentration (Tmax) of mefloquine was significantly shorter after food intake (17 hours) than in the fasting state (36 hours). There was no difference in the elimination half-life of mefloquine and metabolite, or the Tmax for the metabolite.

MANAGEMENT: To ensure maximal oral absorption, mefloquine should be administered immediately after a meal with at least 8 ounces of water.

References

  1. "Product Information. Mefloquine Hydrochloride (mefloquine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation) (2021):
  2. Schmidt LE, Dalhoff K "Food-drug interactions." Drugs 62 (2002): 1481-502

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Moderate

ritonavir food

Applies to: dasabuvir / 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

paritaprevir food

Applies to: dasabuvir / 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

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

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