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Drug Interactions between carfilzomib and ethinyl estradiol / norelgestromin

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

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Interactions between your drugs

Major

ethinyl estradiol carfilzomib

Applies to: ethinyl estradiol / norelgestromin and carfilzomib

GENERALLY AVOID: Venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), have occurred during treatment with carfilzomib, and concurrent use of hormonal contraception also associated with this adverse effect can potentiate the risk. In clinical trials, the reported incidence of venous thromboembolic events was up to 15.3% with carfilzomib plus lenalidomide and dexamethasone versus 9% with lenalidomide and dexamethasone. In addition, the reported incidence of venous thromboembolic events was up to 10.6% with carfilzomib plus dexamethasone versus 3.1% with bortezomib plus dexamethasone. The incidence of thromboembolic events was 2% with carfilzomib monotherapy.

MANAGEMENT: Hormonal contraception associated with a risk of thrombosis should generally be avoided during use of carfilzomib. Advise female and male patients of reproductive potential to use effective contraception or abstain from sexual activity during treatment with carfilzomib for at least 30 and 90 days, respectively, following completion of therapy. Advise the patient to contact their physician immediately if pregnancy does occur during these times.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Faculty of Sexual & Reproductive Healthcare (2016) "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf"
Major

norelgestromin carfilzomib

Applies to: ethinyl estradiol / norelgestromin and carfilzomib

GENERALLY AVOID: Venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), have occurred during treatment with carfilzomib, and concurrent use of hormonal contraception also associated with this adverse effect can potentiate the risk. In clinical trials, the reported incidence of venous thromboembolic events was up to 15.3% with carfilzomib plus lenalidomide and dexamethasone versus 9% with lenalidomide and dexamethasone. In addition, the reported incidence of venous thromboembolic events was up to 10.6% with carfilzomib plus dexamethasone versus 3.1% with bortezomib plus dexamethasone. The incidence of thromboembolic events was 2% with carfilzomib monotherapy.

MANAGEMENT: Hormonal contraception associated with a risk of thrombosis should generally be avoided during use of carfilzomib. Advise female and male patients of reproductive potential to use effective contraception or abstain from sexual activity during treatment with carfilzomib for at least 30 and 90 days, respectively, following completion of therapy. Advise the patient to contact their physician immediately if pregnancy does occur during these times.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. 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

Moderate

ethinyl estradiol food

Applies to: ethinyl estradiol / norelgestromin

MONITOR: Coadministration of ethinyl estradiol may increase the plasma concentrations of drugs that are primarily metabolized by CYP450 1A2. In a study of 30 healthy volunteers administered the CYP450 1A2 substrate tizanidine, the systemic exposure (AUC) of tizanidine was 3.9 times greater in women using an oral contraceptive containing ethinyl estradiol.

MANAGEMENT: Patients should be monitored for increased adverse effects of the CYP450 1A2 substrate during concomitant use with ethinyl estradiol. Product labeling for the specific CYP450 1A2 substrate should be consulted for additional recommendations.

References (1)
  1. Granfors MT, Backman JT, Laitila J, Neuvonen PJ (2005) "Oral contraceptives containing ethinyl estradiol and gestodene markedly increase plasma concentrations and effects of tizanidine by inhibiting cytochrome P450 1A2." Clin Pharmacol Ther, 78, p. 400-11
Minor

ethinyl estradiol food

Applies to: ethinyl estradiol / norelgestromin

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 (2)
  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
Minor

ethinyl estradiol food

Applies to: ethinyl estradiol / norelgestromin

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 (1)
  1. 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 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

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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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