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Drug Interactions between amprenavir and Prograf

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

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Interactions between your drugs

Major

tacrolimus amprenavir

Applies to: Prograf (tacrolimus) and amprenavir

MONITOR CLOSELY: Coadministration with protease inhibitors (PIs) may significantly increase the blood concentrations of tacrolimus. The proposed mechanism is PI inhibition of intestinal and hepatic CYP450 3A4, the isoenzyme responsible for the metabolic clearance of tacrolimus. Enhanced tacrolimus oral bioavailability due to inhibition of intestinal P-glycoprotein (P-gp) efflux transporter may also contribute. There have been numerous reports of tacrolimus interaction with various PI-containing regimens in the medical literature, which necessitated substantial (> 10-fold) reductions or interruptions in tacrolimus dosing.

MANAGEMENT: Caution is advised when tacrolimus is used with protease inhibitors (PIs). Dosage reduction and/or prolongation of the dosing interval for tacrolimus will likely be required. Tacrolimus blood levels and renal function should be checked frequently and the dosage adjusted accordingly, particularly following initiation or discontinuation of PI therapy. Patients should be closely monitored for development of serious adverse effects such as nephrotoxicity, lymphoma and other malignancies, infections, diabetes, neurotoxicity (tremor, paraesthesia, encephalopathy, delirium, coma), hyperkalemia, QT prolongation, myocardial hypertrophy, and hypertension. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References (19)
  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Cakaloglu Y, Tredger JM, Devlin J, Williams R (1994) "Importance of cytochrome p-450IIIA activity in determining dosage and blood levels of FK 506 and cyclosporine in liver transplant recipients." Hepatology, 20, p. 309-16
  3. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  4. (2001) "Product Information. Crixivan (indinavir)." Merck & Co., Inc
  5. (2001) "Product Information. Viracept (nelfinavir)." Agouron Pharma Inc
  6. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  7. (2001) "Product Information. Fortovase (saquinavir)." Roche Laboratories
  8. Jain AK, Venkataramanan R, Shapiro R, et al. (2002) "The interaction between antiretroviral agents and tacrolimus in liver and kidney transplant patients." Liver Transpl, 8, p. 841-5
  9. Jain AK, Venkataramanan R, Shapiro R, et al. (2002) "Interaction between tacrolimus and antiretroviral agents in human immunodeficiency virus-positive liver and kidney transplantation patients." Transplant Proc, 34, p. 1540-1
  10. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  11. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  12. Schonder KS, Shullo MA, Okusanya O (2003) "Tacrolimus and lopinavir/ritonavir interaction in liver transplantation." Ann Pharmacother, 37, p. 1793-6
  13. Jain AB, Venkataramanan R, Eghtesad B, et al. (2003) "Effect of coadministered lopinavir and ritonavir (Kaletra) on tacrolimus blood concentration in liver transplantation patients." Liver Transpl, 9, p. 954-60
  14. (2006) "Product Information. Prezista (darunavir)." Ortho Biotech Inc
  15. Teicher E, Vincent I, Bonhomme-Faivre L, et al. (2007) "Effect of Highly Active Antiretroviral Therapy on Tacrolimus Pharmacokinetics in Hepatitis C Virus and HIV Co-Infected Liver Transplant Recipients in the ANRS HC-08 Study." Clin Pharmacokinet, 46, p. 941-52
  16. Pea F, Tavio M, Pavan F, et al. (2008) "Drop in trough blood concentrations of tacrolimus after switching from nelfinavir to fosamprenavir in four HIV-infected liver transplant patients." Antivir Ther, 13, p. 739-42
  17. Mertz D, Battegay M, Marzolini C, Mayr M (2009) "Drug-Drug Interaction in a Kidney Transplant Recipient Receiving HIV Salvage Therapy and Tacrolimus." Am J Kidney Dis
  18. Barau C, Blouin P, Creput C, Taburet AM, Durrbach A, Furlan V (2009) "Effect of coadministered HIV-protease inhibitors on tacrolimus and sirolimus blood concentrations in a kidney transplant recipient." Fundam Clin Pharmacol, 23, p. 423-5
  19. Tsapepas DS, Webber AB, Aull MJ, Figueiro JM, Saal SD (2011) "Managing the atazanavir-tacrolimus drug interaction in a renal transplant recipient." Am J Health Syst Pharm, 68, p. 138-42

Drug and food interactions

Moderate

tacrolimus food

Applies to: Prograf (tacrolimus)

ADJUST DOSING INTERVAL: Consumption of food has led to a 27% decrease in the bioavailability of orally administered tacrolimus.

MANAGEMENT: Tacrolimus should be administered at least one hour before or two hours after meals.

GENERALLY AVOID: Grapefruit juice has been reported to increase tacrolimus trough concentrations. Data are limited, but inhibition of the CYP450 enzyme system appears to be involved.

MANAGEMENT: The clinician may want to recommend that the patient avoid ingesting large amounts of grapefruit juice while taking tacrolimus.

References (2)
  1. (2001) "Product Information. Prograf (tacrolimus)." Fujisawa
  2. Hooks MA (1994) "Tacrolimus, a new immunosuppressant--a review of the literature." Ann Pharmacother, 28, p. 501-11
Moderate

amprenavir food

Applies to: amprenavir

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.

References (2)
  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. Demarles D, Gillotin C, Bonaventure-Paci S, Vincent I, Fosse S, Taburet AM (2002) "Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice." Antimicrob Agents Chemother, 46, p. 1589-1590

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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