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Drug Interactions between indinavir and Viramune

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

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Interactions between your drugs

Moderate

indinavir nevirapine

Applies to: indinavir and Viramune (nevirapine)

ADJUST DOSE: Coadministration with nevirapine may significantly decrease the plasma concentrations of most protease inhibitors (PIs) except ritonavir. The mechanism is nevirapine induction of PI metabolism via CYP450 3A4. In seven patients with advanced HIV disease who were starting dual nucleoside analogs and nelfinavir (750 mg three times a day) as salvage therapy, mean nelfinavir peak plasma concentration (Cmax), 8-hour area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) decreased by 43%, 50% and 53%, respectively, following addition of nevirapine 3 days later (200 mg daily for 2 weeks followed by 200 mg twice daily for 1 week). The time to reach Cmax was reduced from 4 to 2 hours. Autoinduction of nelfinavir metabolism may have played a role, as supported by a study involving 23 patients in which pre- and post-nevirapine plasma levels of nelfinavir taken presumably after both drugs have reached steady state demonstrated no evidence of a significant pharmacokinetic interaction. In another study, nevirapine decreased the median steady-state Cmax, AUC and Cmin of indinavir (800 mg three times a day) by 11%, 27% and 47%, respectively, after 4 weeks of coadministration in 17 HIV-infected subjects. However, antiretroviral response was significantly greater following addition of nevirapine. Ritonavir added as a pharmacokinetic booster has been shown to counteract the inductive effect of nevirapine in some cases, although a decrease in lopinavir concentrations was demonstrated in a pediatric study involving Kaletra and nevirapine.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, caution is advised if nevirapine is prescribed in combination with PIs, particularly if only one PI is used in the antiretroviral regimen. PI dosages may need to be increased when coadministered with nevirapine, although appropriate dosages with respect to safety and efficacy have not been established.

References

  1. (2001) "Product Information. Viramune (nevirapine)." Boehringer-Ingelheim
  2. Merry C, Barry MG, Mulcahy F, Ryan M, Tjia JF, Halifax KL, Breckenridge AM, Back DJ (1998) "The pharmacokinetics of combination therapy with nelfinavir plus nevirapine." AIDS, 12, p. 1163-7
  3. Skowron G, Leoung C, Kerr B, Dusek A, Anderson R, Beebe S, Grosso R (1998) "Lack of pharmacokinetic interaction between nelfinavir and nevirapine." AIDS, 12, p. 1243-4
  4. Mulcahy F, Barry M, Merry C, Back D (1998) "Nelfinavir and nevirapine interaction?" AIDS, 12, p. 2361
  5. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  6. Barry M, Mulcahy F, Merry C, Gibbons S, Back D (1999) "Pharmacokinetics and potential interactions amongst antiretroviral agents used to treat patients with HIV infection." Clin Pharmacokinet, 36, p. 289-304
  7. Acosta EP, Henry K, Baken L, Page LM, Fletcher CV (1999) "Indinavir concentrations and antiviral effect." Pharmacotherapy, 19, p. 708-12
  8. Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, DelGiudice P, Montagne N, Schapiro JM, Dellamonica P (2000) "Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study." Aids, 14, p. 1333-9
  9. Back D, Gibbons S, Khoo S (2003) "Pharmacokinetic drug interactions with nevirapine." J Acquir Immune Defic Syndr, 34 Suppl 1, S8-14
  10. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  11. Murphey RL, Sommadossi JP, Lamson M, Hall DB, Myers M, Dusek A (1999) "Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1." J Infect Dis, 179, p. 1116-23
View all 11 references

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Drug and food interactions

Moderate

indinavir food

Applies to: indinavir

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).

References

  1. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  2. Yeh KC, Deutsch PJ, Haddix H, Hesney M, Hoagland V, Ju WD, Justice SJ, Osborne B, Sterrett AT, Stone JA, Woolf E, Waldman S (1998) "Single-dose pharmacokinetics of indinavir and the effect of food." Antimicrob Agents Chemother, 42, p. 332-8
  3. Shelton MJ, Wynn HE, Newitt RG, DiFrancesco R (2001) "Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects." J Clin Pharmacol, 41, p. 435-42

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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.

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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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