Drug Interaction Report
6 potential interactions and/or warnings found for the following 2 drugs:
- Cinvanti (aprepitant)
- Pirmella 7/7/7 (ethinyl estradiol / norethindrone)
Interactions between your drugs
ethinyl estradiol aprepitant
Applies to: Pirmella 7/7/7 (ethinyl estradiol / norethindrone), Cinvanti (aprepitant)
ADDITIONAL CONTRACEPTION RECOMMENDED: Aprepitant and its prodrug, fosaprepitant, may reduce the efficacy of low-dose hormonal contraceptives during and for up to 28 days after treatment. The proposed mechanism is aprepitant induction of CYP450 3A4, the isoenzyme partially responsible for the metabolic clearance of contraceptive hormones. According to the product labeling, coadministration of aprepitant (100 mg once a day for 14 days) and an oral contraceptive containing ethinyl estradiol-norethindrone (35 mcg-1 mg) resulted in a 43% decrease in the area under the plasma concentration-time curve (AUC) of ethinyl estradiol and an 8% decrease in the AUC of norethindrone. In another study, coadministration of an oral contraceptive containing ethinyl estradiol-norethindrone on days 1 through 21 and aprepitant on days 8 through 10 (125 mg on day 8 and 80 mg/day on days 9 and 10, with ondansetron 32 mg IV on day 8 and oral dexamethasone 12 mg on day 8 and 8 mg/day on days 9, 10, and 11) resulted in a 19% decrease in the ethinyl estradiol AUC on day 10 and up to a 64% decrease in ethinyl estradiol trough concentrations during days 9 through 21. While there was no effect of aprepitant on the AUC of norethindrone on day 10, up to a 60% decrease in norethindrone trough concentrations was observed during days 9 through 21.
MANAGEMENT: Women using low-dose hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with aprepitant or fosaprepitant. Alternative or additional methods of birth control is recommended during treatment with aprepitant and for one month following the last dose of aprepitant. Data are not available for single-dosing of aprepitant 40 mg. However, since the timing of aprepitant administration relative to ovulation could cause contraceptive failure, the same precaution as for the 125 mg/80 mg regimen should be observed. 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.
References
- (2003) "Product Information. Emend (aprepitant)." Merck & Co., Inc
- (2008) "Product Information. Emend for Injection (fosaprepitant)." Merck & Co., Inc
- Faculty of Sexual & Reproductive Healthcare (2016) "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf"
norethindrone aprepitant
Applies to: Pirmella 7/7/7 (ethinyl estradiol / norethindrone), Cinvanti (aprepitant)
ADDITIONAL CONTRACEPTION RECOMMENDED: Aprepitant and its prodrug, fosaprepitant, may reduce the efficacy of low-dose hormonal contraceptives during and for up to 28 days after treatment. The proposed mechanism is aprepitant induction of CYP450 3A4, the isoenzyme partially responsible for the metabolic clearance of contraceptive hormones. According to the product labeling, coadministration of aprepitant (100 mg once a day for 14 days) and an oral contraceptive containing ethinyl estradiol-norethindrone (35 mcg-1 mg) resulted in a 43% decrease in the area under the plasma concentration-time curve (AUC) of ethinyl estradiol and an 8% decrease in the AUC of norethindrone. In another study, coadministration of an oral contraceptive containing ethinyl estradiol-norethindrone on days 1 through 21 and aprepitant on days 8 through 10 (125 mg on day 8 and 80 mg/day on days 9 and 10, with ondansetron 32 mg IV on day 8 and oral dexamethasone 12 mg on day 8 and 8 mg/day on days 9, 10, and 11) resulted in a 19% decrease in the ethinyl estradiol AUC on day 10 and up to a 64% decrease in ethinyl estradiol trough concentrations during days 9 through 21. While there was no effect of aprepitant on the AUC of norethindrone on day 10, up to a 60% decrease in norethindrone trough concentrations was observed during days 9 through 21.
MANAGEMENT: Women using low-dose hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with aprepitant or fosaprepitant. Alternative or additional methods of birth control is recommended during treatment with aprepitant and for one month following the last dose of aprepitant. Data are not available for single-dosing of aprepitant 40 mg. However, since the timing of aprepitant administration relative to ovulation could cause contraceptive failure, the same precaution as for the 125 mg/80 mg regimen should be observed. 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.
References
- (2003) "Product Information. Emend (aprepitant)." Merck & Co., Inc
- (2008) "Product Information. Emend for Injection (fosaprepitant)." Merck & Co., Inc
- Faculty of Sexual & Reproductive Healthcare (2016) "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf"
Drug and food interactions
norethindrone food
Applies to: Pirmella 7/7/7 (ethinyl estradiol / norethindrone)
MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
MANAGEMENT: Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.
References
- Edgar B, Bailey D, Bergstrand R, et al. (1992) "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance." Eur J Clin Pharmacol, 42, p. 313-7
- Jonkman JH, Sollie FA, Sauter R, Steinijans VW (1991) "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther, 49, p. 248-55
- Bailey DG, Arnold JM, Munoz C, Spence JD (1993) "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther, 53, p. 637-42
- Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
- Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A (1994) "Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation." Pharmazie, 49, p. 522-4
- Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD (1993) "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther, 54, p. 589-94
- Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG (1995) "Drug-food interactions in clinical practice." J Fam Pract, 40, p. 376-84
- (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
- Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
- Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
- Majeed A, Kareem A (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics." Pediatr Nephrol, 10, p. 395
- Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS (1996) "Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice." Br J Clin Pharmacol, 42, p662
- Josefsson M, Zackrisson AL, Ahlner J (1996) "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol, 51, p. 189-93
- Kantola T, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid." Clin Pharmacol Ther, 63, p. 397-402
- Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A (1998) "Interaction between grapefruit juice and diazepam in humans." Eur J Drug Metab Pharmacokinet, 23, p. 55-9
- Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
- Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR (1998) "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther, 64, p. 248-56
- Garg SK, Kumar N, Bhargava VK, Prabhakar SK (1998) "Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther, 64, p. 286-8
- Lilja JJ, Kivisto KT, Neuvonen PJ (1998) "Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors." Clin Pharmacol Ther, 64, p. 477-83
- Fuhr U, Maier-Bruggemann A, Blume H, et al. (1998) "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther, 36, p. 126-32
- Lilja JJ, Kivisto KT, Neuvonen PJ (1999) "Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin." Clin Pharmacol Ther, 66, p. 118-27
- Eagling VA, Profit L, Back DJ (1999) "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, p. 543-52
- Damkier P, Hansen LL, Brosen K (1999) "Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine." Br J Clin Pharmacol, 48, p. 829-38
- Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC (1999) "The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study." Clin Ther, 21, p. 1890-9
- Dresser GK, Spence JD, Bailey DG (2000) "Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition." Clin Pharmacokinet, 38, p. 41-57
- Gunston GD, Mehta U (2000) "Potentially serious drug interactions with grapefruit juice." S Afr Med J, 90, p. 41
- Takanaga H, Ohnishi A, Maatsuo H, et al. (2000) "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol, 49, p. 49-58
- Libersa CC, Brique SA, Motte KB, et al. (2000) "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol, 49, p. 373-8
- Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
- Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E (2001) "Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers." Ther Drug Monit, 23, p. 369-73
- Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K (1993) "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol, 44, p. 295-8
- Flanagan D (2005) "Understanding the grapefruit-drug interaction." Gen Dent, 53, 282-5; quiz 286
ethinyl estradiol food
Applies to: Pirmella 7/7/7 (ethinyl estradiol / norethindrone)
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
- Weber A, Jager R, Borner A, et al. (1996) "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception, 53, p. 41-7
- 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
ethinyl estradiol food
Applies to: Pirmella 7/7/7 (ethinyl estradiol / norethindrone)
The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.
References
- Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80
norethindrone food
Applies to: Pirmella 7/7/7 (ethinyl estradiol / norethindrone)
The central nervous system effects and blood levels of ethanol may be increased in patients taking oral contraceptives, although data are lacking and reports are contradictory. The mechanism may be due to enzyme inhibition. Consider counseling women about this interaction which is unpredictable.
References
- Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80
Therapeutic duplication warnings
No duplication 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.
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
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. | |
No interaction information available. |
Learn more
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
Check Interactions
To view an interaction report containing 4 (or more) medications, please sign in or create an account.
Save Interactions List
Sign in to your account to save this drug interaction list.