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Drug Interactions between Agenerase and Lunelle

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

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Interactions between your drugs

Major

medroxyPROGESTERone amprenavir

Applies to: Lunelle (estradiol / medroxyprogesterone) and Agenerase (amprenavir)

GENERALLY AVOID: Coadministration with some hormonal contraceptives may decrease the plasma concentrations of amprenavir. The mechanism of interaction is unknown. In 10 study subjects coadministered amprenavir (1200 mg twice a day for 28 days) and ethinyl estradiol-norethindrone (0.035 mg-1 mg for 1 cycle), amprenavir systemic exposure (AUC) and trough plasma concentration (Cmin) were reduced by 22% and 20%, respectively, compared to administration of amprenavir alone. Conversely, the Cmin of ethinyl estradiol was increased by 32%, while the Cmin and AUC of norethindrone were increased by 45% and 18%, respectively.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, alternative (i.e., nonhormonal) methods of birth control should be considered in patients treated with amprenavir.

References

  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. 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
  3. (2005) "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care, 31, p. 139-51

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Drug and food interactions

Moderate

amprenavir food

Applies to: Agenerase (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

  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

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Minor

estradiol food

Applies to: Lunelle (estradiol / medroxyprogesterone)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T (1995) "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet, 20, p. 219-24

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.