Skip to main content

Drug Interactions between emtricitabine / nelfinavir / tenofovir and estradiol / medroxyprogesterone

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

medroxyPROGESTERone nelfinavir

Applies to: estradiol / medroxyprogesterone and emtricitabine / nelfinavir / tenofovir

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations and pharmacologic effects of medroxyprogesterone, which is primarily metabolized by the isoenzyme. Aminoglutethimide, a CYP450 3A4 inducer, has been shown to significantly decrease the serum levels of medroxyprogesterone by 50% or more when administered at 250 mg two to four times daily to women with breast cancer receiving high-dose medroxyprogesterone orally. The decrease was accompanied by an increase in serum cortisol level, which suggests diminished adrenal suppressive effect of medroxyprogesterone. The interaction has not been studied with depot formulations of medroxyprogesterone. Because the clearance of medroxyprogesterone is approximately equal to the rate of hepatic blood flow, drugs that induce CYP450 3A4 are not expected to significantly affect the pharmacokinetics of medroxyprogesterone administered parenterally. In one study, no interaction was reported when medroxyprogesterone was administered intravenously with aminoglutethimide.

MANAGEMENT: Pharmacologic response to medroxyprogesterone should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary. When administered as the depot formulation for contraception, no dosage adjustment for medroxyprogesterone is currently recommended during coadministration with CYP450 3A4 inducers. However, consideration may be given to decreasing the dosing interval (e.g., from one injection every 12 weeks to every 10 weeks) if an interaction is suspected.

References

  1. Lundgren S, Lonning PE, Aakvaag A, Kvinnsland S, Lnning PE "Influence of aminoglutethimide on the metabolism of medroxyprogesterone acetate and megestrol acetate in postmenopausal patients with advanced breast cancer." Cancer Chemother Pharmacol 27 (1990): 101-5
  2. Halpenny O, Bye A, Cranny A, Feely J, Daly PA "Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate." Med Oncol Tumor Pharmacother 7 (1990): 241-7
  3. "Product Information. Depo-Provera (medroxyprogesterone)." Pharmacia and Upjohn PROD (2001):
  4. "Product Information. Provera (medroxyprogesterone)." Pharmacia and Upjohn PROD (2001):
  5. Kobayashi K, Mimura N, Fujii H, et al. "Role of human cytochrome P450 3A4 in metabolism of medroxyprogesterone acetate." Clin Cancer Res 6 (2000): 3297-303
  6. "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care 31 (2005): 139-51
  7. O'Brien MD, Guillebaud J "Contraception for women with epilepsy." Epilepsia 47 (2006): 1419-22
View all 7 references

Switch to consumer interaction data

Moderate

estradiol nelfinavir

Applies to: estradiol / medroxyprogesterone and emtricitabine / nelfinavir / tenofovir

MONITOR: Coadministration of conjugated estrogens with ritonavir or nelfinavir may lead to decreased plasma concentrations of conjugated estrogens. The proposed mechanism may involve induction of the CYP450 3A4-mediated metabolism of conjugated estrogens by ritonavir and nelfinavir. Increased metabolism of estrogens may lead to decreased efficacy of the hormone replacement therapy. Ritonavir is a known CYP450 3A4 substrate and inhibitor; however, it has also been shown to reduce plasma concentrations of contraceptive hormones via a possible mechanism involving induction of glucuronosyltransferase and/or CYP450 hydroxylation. In addition, along with being a strong CYP450 3A4 inhibitor, nelfinavir has also been shown to possess CYP450 3A4-inducing properties.

MANAGEMENT: Dosage adjustments as well as increased clinical and laboratory monitoring should be considered whenever ritonavir or nelfinavir is added to or withdrawn from therapy with conjugated estrogens.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  2. Ouellet D, Qian J, Locke CS, Eason CJ, Cavanaugh JH "Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers." Br J Clin Pharmacol 46 (1998): 111-6
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Dixit V, Hariparsad N, Li F, Desai P, Thummel KE, Unadkat JD "Cytochrome P450 enzymes and transporters induced by anti-human immunodeficiency virus protease inhibitors in human hepatocytes: implications for predicting clinical drug interactions." Drug Metab Dispos 35 (2007): 1853-9
  5. Cerner Multum, Inc. "Australian Product Information." O 0
  6. Faculty of Sexual & Reproductive Healthcare "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf" (2016):
View all 6 references

Switch to consumer interaction data

Drug and food interactions

Minor

estradiol food

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

Switch to consumer interaction data

Minor

tenofovir food

Applies to: emtricitabine / nelfinavir / 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):

Switch to consumer interaction data

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.

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