Drug Interaction Report
6 potential interactions and/or warnings found for the following 2 drugs:
- Demulen 1/50 (ethinyl estradiol / ethynodiol)
- ritonavir
Interactions between your drugs
ethinyl estradiol ritonavir
Applies to: Demulen 1/50 (ethinyl estradiol / ethynodiol), ritonavir
ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with ritonavir may decrease the plasma concentrations of contraceptive hormones. In a pharmacokinetic study, 22 of 23 healthy women who received single doses of an oral contraceptive containing ethinyl estradiol 50 mcg and ethynodiol 1 mg had reduced serum levels of ethinyl estradiol following the addition of ritonavir (500 mg twice a day) for 2 weeks. Specifically, the mean peak serum concentration (Cmax) decreased by 32%, the mean systemic exposure (AUC) decreased by 41%, and the mean terminal elimination rate constant increased by 31%. The exact mechanism of interaction is unknown but may involve ritonavir induction of glucuronosyltransferase and/or CYP450 hydroxylation. Since estrogens and progestins may share common routes of metabolism, the possibility of a similar interaction should be considered in patients receiving contraceptive hormones other than ethinyl estradiol.
MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with ritonavir. Alternative or additional methods of birth control should be used during and for at least 4 weeks after ritonavir therapy. If a combination oral contraceptive pill is used, a regimen containing at least 50 mcg of ethinyl estradiol per day or equivalent should be selected. Although breakthrough bleeding is not necessarily indicative of low ethinyl estradiol serum levels or increased risk of ovulation, some clinicians suggest that women who experience breakthrough bleeding during enzyme-inducing therapy may be prescribed an increased dose of ethinyl estradiol above 50 mcg daily by combining more than one formulation of contraceptive pill if necessary. For emergency contraception in patients who have used an hepatic enzyme inducer in the past 4 weeks, a non-hormonal emergency contraceptive (e.g., copper intrauterine device) is considered preferable. If this is not possible, some authorities recommend that the usual dose of levonorgestrel (1.5 mg) should be doubled to 3 mg and taken as a single dose as soon as possible (within 72 hours of unprotected sexual intercourse). However, there are no data on efficacy, compliance, or side effects of this regimen. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action. Injectable progestin-only contraceptives are also thought to be unaffected by enzyme-inducing drugs.
References (1)
- (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
- Ouellet D, Qian J, Locke CS, Eason CJ, Cavanaugh JH (1998) "Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers." Br J Clin Pharmacol, 46, p. 111-6
- (2005) "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care, 31, p. 139-51
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Faculty of Sexual & Reproductive Healthcare (2016) "FSRH Clinical Guidance: Drug Interactions with Hormonal Contraception. file:///C:/Users/df033684/Downloads/ceuguidancedruginteractionshormonal.pdf"
ethynodiol ritonavir
Applies to: Demulen 1/50 (ethinyl estradiol / ethynodiol), ritonavir
ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with ritonavir may decrease the plasma concentrations of contraceptive hormones. In a pharmacokinetic study, 22 of 23 healthy women who received single doses of an oral contraceptive containing ethinyl estradiol 50 mcg and ethynodiol 1 mg had reduced serum levels of ethinyl estradiol following the addition of ritonavir (500 mg twice a day) for 2 weeks. Specifically, the mean peak serum concentration (Cmax) decreased by 32%, the mean systemic exposure (AUC) decreased by 41%, and the mean terminal elimination rate constant increased by 31%. The exact mechanism of interaction is unknown but may involve ritonavir induction of glucuronosyltransferase and/or CYP450 hydroxylation. Since estrogens and progestins may share common routes of metabolism, the possibility of a similar interaction should be considered in patients receiving contraceptive hormones other than ethinyl estradiol.
MANAGEMENT: Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with ritonavir. Alternative or additional methods of birth control should be used during and for at least 4 weeks after ritonavir therapy. If a combination oral contraceptive pill is used, a regimen containing at least 50 mcg of ethinyl estradiol per day or equivalent should be selected. Although breakthrough bleeding is not necessarily indicative of low ethinyl estradiol serum levels or increased risk of ovulation, some clinicians suggest that women who experience breakthrough bleeding during enzyme-inducing therapy may be prescribed an increased dose of ethinyl estradiol above 50 mcg daily by combining more than one formulation of contraceptive pill if necessary. For emergency contraception in patients who have used an hepatic enzyme inducer in the past 4 weeks, a non-hormonal emergency contraceptive (e.g., copper intrauterine device) is considered preferable. If this is not possible, some authorities recommend that the usual dose of levonorgestrel (1.5 mg) should be doubled to 3 mg and taken as a single dose as soon as possible (within 72 hours of unprotected sexual intercourse). However, there are no data on efficacy, compliance, or side effects of this regimen. No precautions or recommendations are available for women using hormone-releasing intrauterine systems, but a significant interaction with these systems is thought to be unlikely due to their local action. Injectable progestin-only contraceptives are also thought to be unaffected by enzyme-inducing drugs.
References (2)
- (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
- Ouellet D, Qian J, Locke CS, Eason CJ, Cavanaugh JH (1998) "Effect of ritonavir on the pharmacokinetics of ethinyl oestradiol in healthy female volunteers." Br J Clin Pharmacol, 46, p. 111-6
- (2005) "FFPRHC Guidance (April 2005). Drug interactions with hormonal contraception." J Fam Plann Reprod Health Care, 31, p. 139-51
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- 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
ritonavir food
Applies to: ritonavir
ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.
MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.
References (3)
- (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
ethinyl estradiol food
Applies to: Demulen 1/50 (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 (4)
- 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: Demulen 1/50 (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 (5)
- Hobbes J, Boutagy J, Shenfield GM (1985) "Interactions between ethanol and oral contraceptive steroids." Clin Pharmacol Ther, 38, p. 371-80
ethynodiol food
Applies to: Demulen 1/50 (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 (6)
- 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. |
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