Possible interactions with "morning-after pill" - double dose or copper IUD required
New recommendations for levonorgestrel emergency contraceptives in case of interactions with CYP3A4-inducing drugs.
In Austria, the current recommendations of the European Medicines Agency are being implemented following a technical review of emergency contraceptives (containing the active ingredient levonorgestrel).
The efficacy of emergency contraceptives containing levonorgestrel ("morning-after pill") may be reduced under certain conditions. This reduction in efficacy occurs when other drugs taken at the same time increase the activity of a specific liver enzyme (CYP3A4). This is referred to as enzyme induction. The active ingredients that trigger such an induction include, for example, St. John's wort preparations, rifampicin, certain HIV medications or antiepileptic drugs (see table below).
Therefore, for women who wish to use emergency contraception with levonorgestrel-containing drugs and who have taken CYP3A4-inducing drugs within the last 4 weeks, there is an increased risk of decreased levonorgestrel plasma levels and thus decreased efficacy of the morning-after pill. This may result in emergency contraception not working reliably at the usual dosage (single dose of 1.5 mg). It is therefore necessary either to switch to alternatives or to double the dose.
Specifically, this means that women who have taken enzyme-inducing drugs within the last 4 weeks and need emergency contraception are recommended to primarily use non-hormonal emergency contraception (i.e., a copper IUD) or, if these women cannot or do not wish to use a copper IUD, to alternatively take a double dose of levonorgestrel, i.e., two tablets together (at 1.5 mg each, for a total of 3 mg).
Note: The alternative active ingredient ulipristal acetate (EllaOne 30 mg tablet), which is also approved for hormonal emergency contraception, is not recommended in the case of the above-described interactions according to the currently available data (neither in single nor double dosage), as it is subject to a particularly significant active ingredient plasma level reduction, in some cases up to more than 90%, when administered simultaneously with CYP3A4-inducing drugs.
The following drug products are approved in Austria:
- Vikela 1.5 mg tablet
- Levodonna 1500 microgram tablet
- Navela 1.5 mg tablet
- Postinor 1500 microgram tablet
- Velafam 750 microgram tablets
Levonorgestrel is an emergency contraceptive used to prevent unintended pregnancy by taking it within 72 hours (3 days) after unprotected intercourse or failure of a contraceptive method. Levonorgestrel works mainly by preventing or delaying ovulation. The sooner the medicine is taken after unprotected intercourse, the more effective it is. It is available either as a single tablet containing 1500 micrograms (= 1.5 mg) of levonorgestrel or as two tablets of 750 micrograms of levonorgestrel each. Examples of CYP3A4 inducers:
- Carbamazepine
- Efavirenz
- Griseofulvin
- St. John's wort
- Phenytoin
- Primidone
- Rifabutin
- Rifampicin
Recommendations for patients:
- Emergency contraception with the pill-after may be used to prevent unintended pregnancy after unprotected intercourse or after a contraceptive breakdown. - Levonorgestrel is an emergency contraceptive used to prevent unintended pregnancy by taking it within 72 hours (3 days) after unprotected intercourse or failure of a contraceptive method. The sooner the medicine is taken after unprotected intercourse, the more effective it is. - Tell your pharmacist or doctor if you are taking or have recently taken any other medicines, including non-prescription or herbal medicines. This is because some medicines may prevent the morning-after pill from working effectively.
- If you have taken any of the following medicines during the last 4 weeks, the "morning after pill" may be less suitable for you: Barbiturates and other medicines used to treat epilepsy (for example, primidone, phenytoin, and carbamazepine).
Medicines used to treat tuberculosis (for example, rifampicin, rifabutin). Medicines for the treatment of HIV (ritonavir, efavirenz).
Medicines used to treat fungal infections (griseofulvin).
Herbal remedies containing St. John's wort (Hypericum perforatum). - Your doctor may then prescribe another type of emergency (non-hormonal) contraception, i.e. a copper IUD. If this is not an option for you, or if it is not possible for you to see your doctor right away, you can take a double dose of Vikela. - Talk to your pharmacist or doctor if you need further advice on the correct dose.
More information:
European Medicines Agency press release (Aug. 09, 2016) link.
Queries:
Dr. Christoph Baumgärtel, Tel.: 050555/36004
E-mail: christoph.baumgaertel@ages.at
Queries (for media):
Communications Management, Tel.: 050555/25000
E-mail: presse@ages.at
