Drug Interactions between ethinyl estradiol / norelgestromin and st. john's wort

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with St. John's wort may reduce the efficacy of contraceptive hormones. The exact mechanism of interaction is unknown but may involve reduced absorption as well as accelerated clearance of the hormones due to induction of intestinal P-glycoprotein drug efflux transporter and intestinal/hepatic CYP450 3A4 metabolism by constituents of St. John's wort. There have been case reports of menstrual breakthrough bleeding following the addition of St. John's wort in patients receiving long-term oral contraceptives, and cases of unplanned pregnancies have also been reported. Between 2000 and 2014, the British Medicines and Healthcare Products Regulatory Agency (MHRA) has received 19 reports of suspected interactions; 15 of which resulted in unintended pregnancies and four resulted in breakthrough bleeding. Clinical trials in healthy female volunteers also demonstrated a higher incidence of breakthrough bleeding during coadministration of low-dose oral contraceptives with St. John's wort compared to administration of the contraceptives alone. However, neither ovarian activity nor endogenous hormone concentrations were affected. St. John's wort also seems to affect the pharmacokinetics of some progestins, probably due to induction of their clearance.

MANAGEMENT: In general, patients should consult a healthcare provider before taking any herbal or alternative medicine. Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with St. John's wort. Alternative or additional methods of birth control should be used during and for at least two weeks after short-term and 4 weeks after long-term (greater than 4 weeks) St. John's wort 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. For women with the etonogestrel subdermal implant, the addition of a barrier method is recommended during concomitant use and for 28 days after discontinuation of hepatic enzyme inducing drugs. It is recommended to remove the implant and to prescribe a nonhormonal method in women who require long-term treatment with hepatic enzyme inducing drugs. 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.

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with St. John's wort may reduce the efficacy of contraceptive hormones. The exact mechanism of interaction is unknown but may involve reduced absorption as well as accelerated clearance of the hormones due to induction of intestinal P-glycoprotein drug efflux transporter and intestinal/hepatic CYP450 3A4 metabolism by constituents of St. John's wort. There have been case reports of menstrual breakthrough bleeding following the addition of St. John's wort in patients receiving long-term oral contraceptives, and cases of unplanned pregnancies have also been reported. Between 2000 and 2014, the British Medicines and Healthcare Products Regulatory Agency (MHRA) has received 19 reports of suspected interactions; 15 of which resulted in unintended pregnancies and four resulted in breakthrough bleeding. Clinical trials in healthy female volunteers also demonstrated a higher incidence of breakthrough bleeding during coadministration of low-dose oral contraceptives with St. John's wort compared to administration of the contraceptives alone. However, neither ovarian activity nor endogenous hormone concentrations were affected. St. John's wort also seems to affect the pharmacokinetics of some progestins, probably due to induction of their clearance.

MANAGEMENT: In general, patients should consult a healthcare provider before taking any herbal or alternative medicine. Women using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant therapy with St. John's wort. Alternative or additional methods of birth control should be used during and for at least two weeks after short-term and 4 weeks after long-term (greater than 4 weeks) St. John's wort 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. For women with the etonogestrel subdermal implant, the addition of a barrier method is recommended during concomitant use and for 28 days after discontinuation of hepatic enzyme inducing drugs. It is recommended to remove the implant and to prescribe a nonhormonal method in women who require long-term treatment with hepatic enzyme inducing drugs. 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.