Skip to main content

Drug Interactions between nelfinavir and saquinavir

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

saquinavir nelfinavir

Applies to: saquinavir and nelfinavir

GENERALLY AVOID: Coadministration with nelfinavir may significantly increase the bioavailability of saquinavir from both the hard gelatin capsule (HGC) and soft gelatin capsule (SGC) formulations. The mechanism is nelfinavir inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of saquinavir. In six HIV+ patients stabilized on their antiretroviral regimen, addition of nelfinavir (750 mg orally three times a day for 2 days) resulted in mean peak plasma concentration (Cmax) and 8-hour area under the concentration-time curve (AUC) for saquinavir (HGC 600 mg three times a day) that were approximately five times those at baseline. In 14 HIV+ patients, coadministration of nelfinavir (750 mg orally three times a day for 4 days) and saquinavir (SGC 1200 mg single dose) yielded increases in saquinavir Cmax and AUC of 179% and 392%, respectively, according to the product labelings. In 18 healthy volunteers, simultaneous administration of nelfinavir (750 mg single oral dose) decreased the clearance of saquinavir (SGC 800 mg single dose) 10-fold compared to when saquinavir was administered alone. Saquinavir had negligible effect on the pharmacokinetics of nelfinavir. In addition, in 12 HIV+ patients administered multiple doses of saquinavir-ritonavir (1000 mg-100 mg twice a day) with nelfinavir (1250 mg twice a day), there were negligible increases in the AUC and Cmax of saquinavir of 13% and 9%, respectively. There were also negligible changes in the AUC and Cmax of nelfinavir, with a reduction of 6% and 5%, respectively.

MANAGEMENT: Due to a high degree of interpatient variability in saquinavir bioavailability, the interaction with nelfinavir may benefit some patients while exposing others to excessively high saquinavir levels and potential toxicity. The combination of ritonavir-boosted saquinavir and nelfinavir is generally not recommended; 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, including elevations in liver function tests and serum creatinine phosphokinase and neutropenia, and the dosage(s) adjusted as necessary.

References (7)
  1. (2001) "Product Information. Invirase (saquinavir)." Roche Laboratories
  2. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  3. Merry C, Barry MG, Mulcahy F, Halifax KL, Back DJ (1997) "Saquinavir pharmacokinetics alone and in combination with nelfinavir in HIV-infected patients." AIDS, 11, f117-20
  4. (2001) "Product Information. Fortovase (saquinavir)." Roche Laboratories
  5. 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
  6. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  7. Cerner Multum, Inc. "Australian Product Information."

Drug and food interactions

Moderate

saquinavir food

Applies to: saquinavir

ADJUST DOSING INTERVAL: Food significantly increases the absorption of saquinavir.

MONITOR: Coadministration with grapefruit juice may increase the plasma concentrations of saquinavir. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In eight healthy volunteers, ingestion of 400 mL of grapefruit juice prior to administration of a 600 mg dose of saquinavir mesylate increased the area under the plasma concentration-time curve and oral bioavailability of saquinavir by 50% and 100%, respectively, compared to water; however, the increase is not considered clinically relevant. A high degree of intersubject variability in the grapefruit juice effect was also observed. The extent to which this interaction may occur with the saquinavir free base soft gelatin capsule is unknown. However, the saquinavir soft gelatin capsule formulation is no longer commercially available.

MANAGEMENT: Saquinavir mesylate should be taken with meals or within 2 hours after eating to enhance bioavailability. Patients should be advised to avoid the consumption of large amounts of grapefruit and grapefruit juice during saquinavir therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation.

References (6)
  1. (2001) "Product Information. Invirase (saquinavir)." Roche Laboratories
  2. Kupferschmidt HHT, Fattinger KE, Ha HR, Follath F, Krahenbuhl S (1998) "Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man." Br J Clin Pharmacol, 45, p. 355-9
  3. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  4. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  6. Cerner Multum, Inc. "Australian Product Information."

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:

  • nelfinavir
  • saquinavir

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.

See also

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer