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Drug Interactions between lopinavir / ritonavir and nevirapine

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

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Interactions between your drugs

Major

nevirapine lopinavir

Applies to: nevirapine and lopinavir / ritonavir

ADJUST DOSE: Coadministration with nevirapine may decrease the plasma concentrations of lopinavir, even in the presence of low-dose ritonavir as a pharmacokinetic booster. The proposed mechanism is nevirapine induction of lopinavir metabolism via CYP450 3A4. In a parallel group study consisting of HIV-1 positive adult subjects, coadministration of lopinavir-ritonavir (400 mg-100 mg capsule twice a day) with nevirapine (200 mg twice a day) to steady-state resulted in a 19% relative decrease in lopinavir peak plasma concentration (Cmax), a 27% relative decrease in systemic exposure (AUC), and a 51% relative decrease in trough plasma concentration (Cmin) in 22 subjects compared to administration of lopinavir-ritonavir alone in 19 subjects. Similar results were reported when the interaction was studied in a pediatric population of HIV-infected subjects ranging in age from 6 months to 12 years. In addition, the pharmacokinetics of lopinavir-ritonavir oral solution 300 mg-75 mg/m2 twice daily with nevirapine (7 mg/kg twice daily in patients 6 months to 8 years and 4 mg/kg twice daily in patients older than 8 years) and 230 mg-57.5 mg/m2 twice daily without nevirapine have been studied in a total of 53 pediatric patients ranging in age from 6 months to 12 years. Both regimens provided lopinavir plasma concentrations similar to those obtained in adult patients receiving the 400 mg-100 mg twice daily regimen without nevirapine. In healthy volunteers, lopinavir-ritonavir did not significantly affect the plasma concentrations of nevirapine. However, due to study discontinuations, there was limited power to detect changes in nevirapine pharmacokinetics in the presence of lopinavir-ritonavir.

MANAGEMENT: A dosage increase is recommended for lopinavir-ritonavir when used in combination with nevirapine. For adults, the dosage should be increased to 500 mg-125 mg (two 200 mg-50 mg tablets and one 100 mg-25 mg tablet) twice daily for the tablets and 533 mg-133 mg (6.5 mL) twice daily for the oral solution. Lopinavir-ritonavir should not be administered as a once daily regimen in combination with nevirapine. For pediatric patients 6 months to 18 years of age, the dosage should be increased to 300 mg-75 mg/m2 twice daily for the oral solution in both treatment-naive and treatment-experienced patients, not to exceed the recommended adult dosage of 533 mg-133 mg (6.5 mL) twice daily. If weight-based dosing is preferred, the recommended dosage is 13 mg-3.25 mg/kg given twice daily for patients under 15 kg and 11 mg-2.75 mg/kg given twice daily for patients 15 kg to 45 kg. Pediatric patients weighing more than 45 kg should receive the adult dosage of lopinavir-ritonavir. Please consult the manufacturer's product labeling for pediatric dosing of the tablet formulation. Lopinavir-ritonavir should not be administered in combination with nevirapine in patients under 6 months of age due to the lack of clinical data.

References (5)
  1. (2001) "Product Information. Kaletra (lopinavir-ritonavir)." Abbott Pharmaceutical
  2. Benson CA, Deeks SG, Brun SC, et al. (2002) "Safety and antiviral activity at 48 weeks of lopinavir/ritonavir plus nevirapine and 2 nucleoside reverse-transcriptase inhibitors in human immunodeficiency virus type 1--infected protease inhibitor--experienced patients." J Infect Dis, 185, p. 599-607
  3. Back D, Gibbons S, Khoo S (2003) "Pharmacokinetic drug interactions with nevirapine." J Acquir Immune Defic Syndr, 34 Suppl 1, S8-14
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink

Drug and food interactions

Moderate

ritonavir food

Applies to: lopinavir / 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
Moderate

lopinavir food

Applies to: lopinavir / ritonavir

ADJUST DOSING INTERVAL: Food significantly increases the bioavailability of lopinavir from the oral solution formulation of lopinavir-ritonavir. Relative to fasting, administration of lopinavir-ritonavir oral solution with a moderate-fat meal (500 to 682 Kcal; 23% to 25% calories from fat) increased lopinavir peak plasma concentration (Cmax) and systemic exposure (AUC) by 54% and 80%, respectively, whereas administration with a high-fat meal (872 Kcal; 56% from fat) increased lopinavir Cmax and AUC by 56% and 130%, respectively. No clinically significant changes in Cmax and AUC were observed following administration of lopinavir-ritonavir tablets under fed conditions versus fasted conditions. Relative to fasting, administration of a single 400 mg-100 mg dose (two 200 mg-50 mg tablets) with a moderate-fat meal (558 Kcal; 24.1% calories from fat) increased lopinavir Cmax and AUC by 17.6% and 26.9%, respectively, while administration with a high-fat meal (998 Kcal; 51.3% from fat) increased lopinavir AUC by 18.9% but not Cmax. Relative to fasting, ritonavir Cmax and AUC also increased by 4.9% and 14.9%, respectively, with the moderate-fat meal and 10.3% and 23.9%, respectively, with the high-fat meal.

MANAGEMENT: Lopinavir-ritonavir oral solution should be taken with meals to enhance bioavailability and minimize pharmacokinetic variability. Lopinavir-ritonavir tablets may be taken without regard to meals.

References (1)
  1. (2001) "Product Information. Kaletra (lopinavir-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.

Further information

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