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Drug Interactions between AccessPak for HIV PEP Basic and Invirase

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

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Interactions between your drugs

Moderate

saquinavir tenofovir

Applies to: Invirase (saquinavir) and AccessPak for HIV PEP Basic (emtricitabine / tenofovir)

MONITOR: Coadministration with ritonavir, with or without lopinavir, has been suggested in postmarketing reports to increase the proximal tubular intracellular concentrations of tenofovir and potentiate the risk of tenofovir-induced nephrotoxicity. The proposed mechanism is ritonavir inhibition of tenofovir renal tubular secretion into the urine via multidrug resistance protein MRP2. Analysis of data from a compassionate access study in which 271 patients with advanced HIV disease received the combination for a mean duration of 63 weeks revealed no clinically significant nephrotoxicity associated with coadministration. However, there have been case reports of renal failure associated with acute tubular necrosis, Fanconi's syndrome, and nephrogenic diabetes insipidus in patients treated with tenofovir disoproxil fumarate in combination with ritonavir. Some patients had incomplete recovery of renal function more than a year after cessation of tenofovir therapy. Ritonavir given in combination with lopinavir has also been reported to modestly increase the plasma concentrations of tenofovir. In contrast, both slight decreases and no change in lopinavir and ritonavir concentrations have been reported.

MANAGEMENT: Caution is advised if tenofovir disoproxil fumarate is prescribed with ritonavir. Renal function should be monitored regularly, including surveillance for signs of tubulopathy such as glycosuria, acidosis, increases in serum creatinine level, electrolyte disturbances (e.g., hypokalemia, hypophosphatemia), and proteinuria. The same precaution may be applicable during therapy with other protease inhibitors based on their similar pharmacokinetic profile, although clinical data are lacking. Nelfinavir reportedly does not alter the pharmacokinetics of tenofovir, or vice versa. Tenofovir administration should be discontinued promptly if nephropathy develops.

References

  1. "Product Information. Viread (tenofovir)." Gilead Sciences (2001):
  2. Verhelst D, Monge M, Meynard JL, et al. "Fanconi syndrome and renal failure induced by tenofovir: A first case report." Am J Kidney Dis 40 (2002): 1331-3
  3. Creput C, Gonzalez-Canali G, Hill G, Piketty C, Kazatchkine M, Nochy D "Renal lesions in HIV-1-positive patient treated with tenofovir." AIDS 17 (2003): 935-7
  4. Karras A, Lafaurie M, Furco A, et al. "Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, fanconi syndrome, and nephrogenic diabetes insipidus." Clin Infect Dis 36 (2003): 1070-3
  5. Kearney BP, Mittan A, Sayre J, et al. "Pharmacokinetic drug interaction and long term safety profile of tenofovir DF and lopinavir/ritonavir. http://www.icaac.org/ICAAC.asp" (2003):
  6. Rollot F, Nazal EM, Chauvelot-Moachon L, et al. "Tenofovir-related fanconi syndrome with nephrogenic diabetes insipidus in a patient with acquired immunodeficiency syndrome: the role of lopinavir-ritonavir-Didanosine." Clin Infect Dis 37 (2003): E174-6
  7. Zimmermann AE, Pizzoferrato T, Bedford J, Morris A, Hoffman R, Braden G "Tenofovir-associated acute and chronic kidney disease: a case of multiple drug interactions." Clin Infect Dis 42 (2006): 283-90
  8. Kapadia J, Shah S, Desai C, et al. "Tenofovir induced Fanconi syndrome: a possible pharmacokinetic interaction." Indian J Pharmacol 45 (2013): 191-2
View all 8 references

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Drug and food interactions

Moderate

saquinavir food

Applies to: Invirase (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

  1. "Product Information. Invirase (saquinavir)." Roche Laboratories PROD (2001):
  2. Kupferschmidt HHT, Fattinger KE, Ha HR, Follath F, Krahenbuhl S "Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man." Br J Clin Pharmacol 45 (1998): 355-9
  3. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  4. Eagling VA, Profit L, Back DJ "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 (1999): 543-52
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. Cerner Multum, Inc. "Australian Product Information." O 0
View all 6 references

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Minor

tenofovir food

Applies to: AccessPak for HIV PEP Basic (emtricitabine / tenofovir)

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.

References

  1. "Product Information. Viread (tenofovir)." Gilead Sciences (2001):

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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.

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