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Drug Interactions between Demulen and Lynparza

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

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Interactions between your drugs

Moderate

ethinyl estradiol olaparib

Applies to: Demulen (ethinyl estradiol / ethynodiol) and Lynparza (olaparib)

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with olaparib may decrease the plasma concentrations and efficacy of contraceptive hormones. The proposed mechanism is olaparib induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of sex hormones. Clinical data are lacking.

MANAGEMENT: Some authorities recommend that women avoid pregnancy during olaparib treatment due to its potential teratogenic effects. In women of childbearing potential, alternative or additional non-hormonal methods of birth control should be considered during treatment and for one month after receiving the last dose of olaparib. Regular pregnancy tests are also recommended. 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

  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"

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Moderate

ethynodiol olaparib

Applies to: Demulen (ethinyl estradiol / ethynodiol) and Lynparza (olaparib)

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with olaparib may decrease the plasma concentrations and efficacy of contraceptive hormones. The proposed mechanism is olaparib induction of CYP450 3A4, the isoenzyme primarily responsible for the metabolic clearance of sex hormones. Clinical data are lacking.

MANAGEMENT: Some authorities recommend that women avoid pregnancy during olaparib treatment due to its potential teratogenic effects. In women of childbearing potential, alternative or additional non-hormonal methods of birth control should be considered during treatment and for one month after receiving the last dose of olaparib. Regular pregnancy tests are also recommended. 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

  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"

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Drug and food interactions

Major

olaparib food

Applies to: Lynparza (olaparib)

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of olaparib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In a drug interaction study with 57 patients, olaparib systemic exposure (AUC) was increased approximately 2.7-fold by the potent CYP450 3A4 inhibitor itraconazole. Simulations using physiologically-based pharmacokinetic (PBPK) models suggest that a moderate inhibitor (fluconazole) may increase the AUC of olaparib by 2-fold. The interaction has not been studied with grapefruit juice. 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. Increased exposure to olaparib may increase the risk of adverse effects such as hematologic toxicity, nausea, vomiting, diarrhea, anorexia, dyspepsia, and abdominal pain or discomfort.

MANAGEMENT: Patients treated with olaparib should avoid consumption of grapefruit, grapefruit juice, starfruit (carambola), and Seville oranges.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2014) "Product Information. Lynparza (olaparib)." Astra-Zeneca Pharmaceuticals

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Minor

ethinyl estradiol food

Applies to: Demulen (ethinyl estradiol / ethynodiol)

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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Minor

ethinyl estradiol food

Applies to: Demulen (ethinyl estradiol / ethynodiol)

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. Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80

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Minor

ethynodiol food

Applies to: Demulen (ethinyl estradiol / ethynodiol)

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. Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80

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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.

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