Progestogen (hormonal contraception)
Levonorgestrel is a hormone (progestogen) used for emergency contraception (the “morning-after pill”) and in several hormonal contraceptive methods. For emergency contraception, it should be taken as soon as possible after unprotected sex.
Also known as: Levonelle, Postinor
Carbamazepine can reduce the effectiveness of levonorgestrel (including emergency contraception). If you take both, talk to your doctor or pharmacist.
Carbamazepine induces CYP3A4 and glucuronidation, accelerating levonorgestrel elimination and reducing contraceptive effectiveness — the levonorgestrel OTC label explicitly warns that seizure medicines can reduce effectiveness, and the Prontuário states that enzyme inducers (barbiturates, phenytoin, primidone, carbamazepine, rifampicin) reduce the effectiveness of progestogens. In regular hormonal contraception, an alternative or complementary method is recommended; for emergency contraception, the copper IUD is the reliable alternative.
Enzyme inducers (carbamazepine, phenytoin, rifampicin, barbiturates) accelerate progestogen metabolism and reduce contraceptive effectiveness. For emergency contraception with levonorgestrel, consider an alternative (ulipristal acetate is not a reliable alternative with inducers; copper IUD).
CYP3A4 induction, accelerating levonorgestrel metabolism.
Contraceptive effectiveness; irregular cycles may indicate reduced hormonal exposure.
Unplanned pregnancy; irregular bleeding.
Use a non-hormonal contraceptive (copper IUD) or an additional barrier method; for emergency contraception, prefer the copper IUD.
DailyMed/FDA (NIH/NLM) — approved Levonorgestrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07567b80-d8a1-41c0-95e4-33afa584bbc4 ; approved Carbamazepine label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=9f3d91cd-a959-4e07-a51b-8a4e9ba9ece2 ; PubMed — https://pmc.ncbi.nlm.nih.gov/articles/PMC2848501/ ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Phenytoin can reduce the effectiveness of levonorgestrel. If you take both, consider an additional or alternative contraceptive method.
Phenytoin is an enzyme inducer that accelerates the metabolism of levonorgestrel and other progestogens, compromising contraceptive effectiveness. The Prontuário lists phenytoin among the inducers that reduce progestogen effectiveness, and the levonorgestrel OTC label warns that seizure medicines can reduce effectiveness. In women with epilepsy on hormonal contraception, a non-hormonal method or high-oestrogen hormonal contraception is recommended according to clinical guidance.
Enzyme inducers (phenytoin) reduce progestogen effectiveness. Recommend a non-hormonal method (copper IUD) or an additional barrier method; for emergency contraception, the copper IUD.
Enzyme induction, accelerating levonorgestrel metabolism.
Contraceptive effectiveness and cycle regularity.
Unplanned pregnancy.
Use a copper IUD or an additional barrier method; reassess contraception with the doctor.
DailyMed/FDA (NIH/NLM) — approved Levonorgestrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07567b80-d8a1-41c0-95e4-33afa584bbc4 ; approved Phenytoin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ef4e97a7-cd18-47a9-a016-2eca5481a87e ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Rifampicin can reduce the effectiveness of levonorgestrel. The medicine label itself advises asking a doctor if you take rifampicin (tuberculosis treatment).
The levonorgestrel over-the-counter label (DailyMed) explicitly instructs asking a doctor or pharmacist before use if taking efavirenz or rifampicin (tuberculosis treatment) or seizure medicines, as these can reduce the effectiveness of levonorgestrel. Rifampicin induces CYP3A4 and accelerates progestogen elimination. In patients with tuberculosis, hormonal emergency contraception is unreliable — the copper IUD is the alternative.
The levonorgestrel OTC label warns that rifampicin can reduce effectiveness. In patients taking rifampicin, prefer the copper IUD for emergency contraception and a non-hormonal method for regular contraception.
CYP3A4 induction by rifampicin, accelerating levonorgestrel elimination.
Contraceptive effectiveness.
Unplanned pregnancy.
Prefer the copper IUD for emergency contraception; a non-hormonal method for regular contraception during rifampicin.
DailyMed/FDA (NIH/NLM) — approved Levonorgestrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07567b80-d8a1-41c0-95e4-33afa584bbc4 ; approved Rifampicin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; Prontuário Terapêutico do INFARMED (11th ed., 2012)
Oral contraceptives can be taken with or without food; taking them with food may reduce nausea.
Take at the same time every day, with or without food.
DailyMed/FDA (NIH/NLM) — approved Levonorgestrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07567b80-d8a1-41c0-95e4-33afa584bbc4
Grapefruit juice can raise ethinylestradiol/levonorgestrel concentrations (CYP3A4 inhibition), with a risk of oestrogenic adverse effects.
Avoid grapefruit juice while using hormonal contraceptives.
DailyMed/FDA (NIH/NLM) — approved Levonorgestrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07567b80-d8a1-41c0-95e4-33afa584bbc4
Combined hormonal contraceptives are contraindicated in patients with a history of venous or arterial thrombosis (increased risk of thromboembolic events).
Do not use combined contraceptives; consider oestrogen-free methods.
DailyMed/FDA (NIH/NLM) — approved Levonorgestrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07567b80-d8a1-41c0-95e4-33afa584bbc4
Uncontrolled hypertension is a relative/absolute contraindication to combined contraceptives (risk of stroke and cardiovascular events).
Control blood pressure before starting; consider an alternative if BP remains elevated.
DailyMed/FDA (NIH/NLM) — approved Levonorgestrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07567b80-d8a1-41c0-95e4-33afa584bbc4
Emergency contraception with levonorgestrel is not teratogenic (extensive data show no increase in malformation risk), but it must not be used as a regular method.
Do not use if pregnancy is already confirmed (it will not be effective); after inadvertent use in pregnancy, there is no indication to terminate.
Levonorgestrel is excreted into milk in small amounts; it can be used during breastfeeding for emergency contraception.
Occasional use as emergency contraception; it does not replace regular contraception.
DailyMed/FDA (NIH/NLM) — approved Levonorgestrel label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07567b80-d8a1-41c0-95e4-33afa584bbc4
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Progestin used in combined oral contraception (with ethinyl estradiol) and in emergency contraception. In oral contraceptives, pregnancy prevention results mainly from suppression of ovulation.
Levonorgestrel is a progestin that suppresses ovulation (main mechanism in combined contraceptives), increases cervical mucus viscosity and alters the endometrium.
Levonorgestrel is completely absorbed (bioavailability of nearly 100%, without first-pass metabolism), with peak plasma concentrations in about 1.3 hours; ethinyl estradiol has a bioavailability of about 43%. Levonorgestrel is 97.5 to 99% protein-bound, mainly to SHBG.
After absorption, levonorgestrel is conjugated at the 17-beta-OH position (sulfate and, to a lesser extent, glucuronide); the phase I metabolites are excreted mainly as glucuronides. Ethinyl estradiol undergoes hepatic 2-hydroxylation by CYP3A4. About 45% of levonorgestrel and its metabolites is excreted in urine and 32% in faeces.
The terminal half-life of levonorgestrel is about 34 hours and that of ethinyl estradiol about 18 hours; ethinyl estradiol undergoes enterohepatic recirculation.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
