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Drug Interactions between indinavir and Viekira XR

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

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Interactions between your drugs

Moderate

ritonavir indinavir

Applies to: Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir) and indinavir

ADJUST DOSE: Coadministration with ritonavir may significantly increase the plasma concentrations of indinavir. The mechanism is ritonavir inhibition of indinavir metabolism via CYP450 3A4. In a study with healthy volunteers, ritonavir (200 mg to 400 mg every 12 hours) increased the peak plasma concentration (Cmax) and systemic exposure (AUC) of indinavir by up to 110% and 475%, respectively, compared to administration of indinavir alone. Increasing indinavir concentrations may increase the risk of urological complications, such as nephrolithiasis. However, increasing ritonavir dosage did not yield proportional increases in indinavir Cmax and AUC. Ritonavir reduced intersubject variability in indinavir plasma levels and has also been shown to eliminate food effects on the bioavailability of indinavir. Indinavir had negligible effect on the pharmacokinetics of ritonavir.

MANAGEMENT: Based on the magnitude of interaction, indinavir dosage should be reduced when coadministered with ritonavir. A regimen of (indinavir:ritonavir) 400:400 mg twice a day with food has been well tolerated in clinical trials and is recommended by some HIV experts. This dosing reportedly produces comparable indinavir AUC as standard indinavir (i.e., unboosted indinavir 800 mg three times a day) but increases plasma trough levels by 4-fold and reduces Cmax by over 50%, which may enhance dosing convenience as well as the safety-to-efficacy profile of indinavir. Lower doses of ritonavir (100 to 200 mg) plus 800 mg of indinavir twice daily with food are also recommended by HIV experts. These regimens appear to be equally effective as standard indinavir but may be somewhat less well tolerated, as indicated by an increased rate of treatment discontinuation and adverse effects such as nephrolithiasis, taste disturbances, and gastrointestinal intolerance in some studies. One trial also found that ritonavir-boosted indinavir (800:100 mg twice daily) had poorer tolerability and caused greater plasma lipid increases than ritonavir-boosted saquinavir (1000:100 mg twice daily), although virologic responses were similar. Limited data suggest that once-daily regimens with indinavir 1200 mg and ritonavir 200 to 400 mg may also be efficacious and warrant further investigation.

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  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. Hsu A, Granneman GR, Cao GL, Carothers L, Japour A, ElShourbagy T, Dennis S, Berg J, Erdman K, Leonard JM, Sun EG (1998) "Pharmacokinetic interaction between ritonavir and indinavir in healthy volunteers." Antimicrob Agents Chemother, 42, p. 2784-91
  4. vanHeeswijk RPG, Veldkamp AI, Hoetelmans RMW, Mulder JW, Schreij G, Hsu A, Lange JMA, Beijnen JH, Meenhorst PL (1999) "The steady-state plasma pharmacokinetics of indinavir alone and in combination with a low dose of ritonavir in twice daily dosing regimens in HIV-1-infected individuals." AIDS, 13, f95-9
  5. Burger DM, Hugen PWH, vanderEnde ME, vanWijngaarden P, Aarnoutse RE, Reiss P, Lange JMA (2000) "Once-daily indinavir plus ritonavir: preliminary results of the PIPO study." Aids, 14, p. 2621-3
  6. Rathbun RC, Rossi DR (2002) "Low-dose ritonavir for protease inhibitor pharmacokinetic enhancement." Ann Pharmacother, 36, p. 702-6
  7. Burger D, Boyd M, Duncombe C, et al. (2003) "Pharmacokinetics and pharmacodynamics of indinavir with or without low-dose ritonavir in HIV-infected Thai patients." J Antimicrob Chemother, 51, p. 1231-8
  8. Aarnoutse RE, Wasmuth JC, Fatkenheuer G, et al. (2003) "Administration of indinavir and low-dose ritonavir (800/100 mg twice daily) with food reduces nephrotoxic peak plasma levels of indinavir." Antivir Ther, 8, p. 309-14
  9. Developed by the panel of Clinical Practices for Treatment of HIV Infection convened by the Department of Health and Human Services (DHHS) (2004) Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. http://AIDSinfo.nih.gov
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  11. Cerner Multum, Inc. "Australian Product Information."
View all 11 references

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Moderate

indinavir paritaprevir

Applies to: indinavir and Viekira XR (dasabuvir / 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. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC

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Drug and food interactions

Moderate

ritonavir food

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

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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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Moderate

paritaprevir food

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

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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:

  • indinavir
  • Viekira XR (dasabuvir/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.