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Drug Interactions between nelfinavir and ritonavir

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

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Interactions between your drugs

Moderate

ritonavir nelfinavir

Applies to: ritonavir and nelfinavir

ADJUST DOSE: Coadministration with ritonavir may significantly increase the plasma concentrations of nelfinavir. The mechanism is ritonavir inhibition of CYP450 3A4 metabolism of nelfinavir. According to the nelfinavir product labeling, ritonavir (500 mg orally every 12 hours for 3 doses) increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of nelfinavir (750 mg single dose) by 44% and 152%, respectively, in 10 subjects (HIV status not stated). In a study involving 18 healthy volunteers, simultaneous administration of ritonavir (400 mg single oral dose) decreased the clearance of nelfinavir (750 mg single dose) 2-fold compared to when nelfinavir was administered alone. Nelfinavir had negligible effect on the pharmacokinetics of ritonavir.

MANAGEMENT: Alteration in dosages or regimen is recommended by the manufacturer of nelfinavir during concomitant therapy with ritonavir. However, appropriate dosages for the combination, with respect to safety and efficacy, have not been established. Patients receiving the combination should be closely monitored for toxicity such as elevations in liver function tests and undue gastrointestinal disturbances, and the dosage(s) adjusted as necessary.

References (4)
  1. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  2. Kempf DJ, Marsh KC, Kumar G, et al. (1997) "Pharmacokinetic enhancement of inhibitors of the human immunodeficiency virus protease by coadministration with ritonavir." Antimicrob Agents Chemother, 41, p. 654-60
  3. Kempf D, Marsh K, Denissen J, Kumar G, Rodrigues D, McDonald E, Flentge C, Green B, Chen X, Leonard J, Norbeck D (1996) "Coadministration with ritonavir enhances the plasma levels of HIV protease inhibitors by inhibition of cytochrome P450." 3rd Conf Retro and Opportun Infect, p. 79
  4. Lu JF, Blaschke TF, Flexner C, Rosenkranz SL, Sheiner LB (2002) "Model-based Analysis of the Pharmacokinetic Interactions Between Ritonavir, Nelfinavir, and Saquinavir after Simultaneous and Staggered Oral Administration." Drug Metab Dispos, 30, p. 1455-61

Drug and food interactions

Moderate

ritonavir food

Applies to: 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)
  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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.

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