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Drug Interactions between enzalutamide and Nuvelle TS Phase I

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

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Interactions between your drugs

Moderate

estradiol enzalutamide

Applies to: Nuvelle TS Phase I (estradiol) and enzalutamide

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of estrogens and progestins. Estrogens have been shown in in vitro and in vivo studies to be partially metabolized by CYP450 3A4, and other steroids including progestins are also believed to undergo metabolism by this isoenzyme. The interaction has been reported primarily with oral contraceptives. There have been case reports of menstrual breakthrough bleeding or unwanted pregnancy in women receiving low-dose oral contraceptives following the addition of known CYP450 3A4 inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort. Inadequate response to estrogen replacement therapy has also been reported in a patient treated with phenytoin. Aminoglutethimide, a CYP450 3A4 inducer, has been shown to decrease medroxyprogesterone and megestrol serum levels by 74% in six patients stabilized on their progestin regimen.

MANAGEMENT: Pharmacologic response to estrogens and progestins should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the hormone dosage adjusted as necessary. For patients receiving hormonal contraceptives, additional or alternative non-hormonal birth control may be advisable during concomitant therapy with CYP450 3A4 inducers. Additional or alternative non-hormonal birth control may be recommended beyond discontinuation of the CYP450 3A4 inducer(s). Individual product labeling should be consulted for specific time frames. Intrauterine systems are unlikely to be significantly affected because of their local action. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed. Patients should be advised to notify their physician if they experience inadequate control of symptoms associated with estrogen deficiency (e.g., nocturnal sweating, vasomotor disturbances, atrophic vaginitis) or changes in the uterine bleeding profile.

References

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  2. Venkatesan K (1992) "Pharmacokinetic drug interactions with rifampicin." Clin Pharmacokinet, 22, p. 47-65
  3. Borcherding SM, Baciewicz AM, Self TH (1992) "Update on rifampin drug interactions." Arch Intern Med, 152, p. 711-6
  4. Weber JC (1984) "Interaction between oral contraceptives and griseofulvin." Br Med J, 288, p. 1125-6
  5. McDaniel PA, Caldroney RD (1986) "Oral contraceptives and griseofulvin interaction." Drug Intell Clin Pharm, 20, p. 384
  6. Cote J (1990) "Interaction of griseofulvin and oral contraceptives." J Am Acad Dermatol, 22, p. 124-5
  7. Baciewicz AM (1985) "Oral contraceptive drug interactions." Ther Drug Monit, 7, p. 26-35
  8. Skolnick JL, Stoler BS, Katz DB, Anderson WH (1976) "Rifampin, oral contraceptives, and pregnancy." JAMA, 236, p. 1382
  9. Lundgren S, Lonning PE, Aakvaag A, Kvinnsland S, Lnning PE (1990) "Influence of aminoglutethimide on the metabolism of medroxyprogesterone acetate and megestrol acetate in postmenopausal patients with advanced breast cancer." Cancer Chemother Pharmacol, 27, p. 101-5
  10. Halpenny O, Bye A, Cranny A, Feely J, Daly PA (1990) "Influence of aminoglutethimide on plasma levels of medroxyprogesterone acetate." Med Oncol Tumor Pharmacother, 7, p. 241-7
  11. Mumford JP (1974) "Letter: Drugs affecting oral contraceptives." Br Med J, 2, p. 333-4
  12. Back DJ, Bates M, Bowden A, et al. (1980) "The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy." Contraception, 22, p. 495-503
  13. Dossetor J (1975) "Drug interactions with oral contraceptives." Br Med J, 4, p. 467-8
  14. Baciewicz AM, Self TH (1984) "Rifampin drug interactions." Arch Intern Med, 144, p. 1667-71
  15. Nocke-finck L (1973) "Effects of rifampicin on menstral cycle and on estrogen excretion in patients taking oral contraceptives." JAMA, 226, p. 378
  16. Bolt HM, Bolt M, Kappus H (1977) "Interaction of rifampicin treatment with pharmacokinetics and metabolism of ethinyloestradiol in man." Acta Endocrinol (Copenh), 85, p. 189-97
  17. Back DJ, Breckenridge AM, Crawford FE, et al. (1980) "The effect of rifampicin on the pharmacokinetics of ethynylestradiol in women." Contraception, 21, p. 135-43
  18. Furlan AJ, Rothner AD (1974) "Anti-epileptic drugs and failure of oral contraceptives." Lancet, 1, p. 1113
  19. Coulam CB, Annegers JF (1979) "Do anticonvulsants reduce the efficacy of oral contraceptives?" Epilepsia, 20, p. 519-26
  20. Szoka PR, Edgren RA (1988) "Drug interactions with oral contraceptives: compilation and analysis of an adverse experience report database." Fertil Steril, 49, s31-8
  21. Mattson RH, Cramer JA, Darney PD, Naftolin F (1986) "Use of oral contraceptives by women with epilepsy." JAMA, 256, p. 238-40
  22. van Dijke CP, Weber JC (1984) "Interaction between oral contraceptives and griseofulvin." Br Med J (Clin Res Ed), 288, p. 1125-6
  23. Laengner H, Detering K (1974) "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet, 2, p. 600
  24. Janz D, Schmidt D (1974) "Letter: Anti-epileptic drugs and failure of oral contraceptives." Lancet, 1, p. 1113
  25. Curran MA (1986) "Drug interactions with the pill." Med J Aust, 144, p. 670-1
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  27. D'Arcy PF (1986) "Drug interactions with oral contraceptives." Drug Intell Clin Pharm, 20, p. 353-62
  28. Notelovitz M, Tjapkes J, Ware M (1981) "Interaction between estrogen and dilantin in a menopausal woman." N Engl J Med, 304, p. 788-9
  29. (2001) "Product Information. Premarin (conjugated estrogens)." Wyeth-Ayerst Laboratories
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  35. Weisberg E (1999) "Interactions between oral contraceptives and antifungals antibacterials - Is contraceptive failure the result?." Clin Pharmacokinet, 36, p. 309-13
  36. Klosterskov Jensen P, Saano V, Haring P, Svenstrup B, Menge GP (1992) "Possible interaction between oxcarbazepine and an oral contraceptive." Epilepsia, 33, p. 1149-52
  37. Wilbur K, Ensom MHH (2000) "Pharmacokinetic drug interactions between oral contraceptives and second-generation anticonvulsants." Clin Pharmacokinet, 38, p. 355-65
  38. Durr D, Stieger B, KullakUblick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K (2000) "St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4." Clin Pharmacol Ther, 68, p. 598-604
  39. Weaver K, Glasier A (1999) "Interaction between broad-spectrum antibiotics and the combined oral contraceptive pill: a literature review." Contraception, 59, p. 71-8
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  42. (2003) "Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception." Br J Clin Pharmacol, 55, p. 112-113
  43. Pfrunder A, Schiesser M, Gerber S, Haschke M, Bitzer J, Drewe J (2003) "Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial." Br J Clin Pharmacol, 56, p. 683-90
  44. Hall SD, Wang Z, Huang SM, et al. (2003) "The interaction between St John's wort and an oral contraceptive." Clin Pharmacol Ther, 74, p. 525-35
  45. Gorski JC, Hamman MA, Wang Z, Vasvada N, Huang S, Hall SD (2002) "The effect of St. John's wort on the efficacy of oral contraception." Clin Pharmacol Ther, 71, P25
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View all 47 references

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Drug and food interactions

Minor

estradiol food

Applies to: Nuvelle TS Phase I (estradiol)

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.

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