ethinylestradiol/levonorgestrel
Combined hormonal contraceptive· Brands: Microgynon, Levlen, Ovranette, Rigevidon, Alesse, LogynonPO
Mechanism of action
Combined hormonal contraceptives work by suppressing ovulation through combined actions on the hypothalamus and pituitary. The estrogen component inhibits follicle-stimulating hormone, while the progestogen inhibits luteinising hormone, preventing follicular maturation and release of the ovum. Additionally, the progestogen thickens cervical mucus, impeding sperm penetration, and alters endometrial histology to reduce implantation likelihood.
Pharmacokinetics
Both components are absorbed from the gastrointestinal tract, with ethinylestradiol undergoing extensive first-pass metabolism in the liver. Levonorgestrel is rapidly and almost completely absorbed, and is highly bound to sex hormone binding globulin. Both are metabolised by cytochrome P450 enzymes, mainly CYP3A4 for ethinylestradiol. The metabolites are excreted in urine and faeces. The half-life of ethinylestradiol is about 24 hours, and that of levonorgestrel is about 24 to 32 hours, with steady state reached after approximately 1 week of daily dosing.
Indications & dosing
Contraception
Take one tablet daily for 21 days, then 7 tablet-free days (or follow pack instructions).
- adult · PO: 1 tablet once daily · Take one tablet daily for 21 days, then 7 tablet-free days (or follow pack instructions).
Acne vulgarisoff-label
Considered off-label for acne; use when other treatments have failed.
- adult · PO: 1 tablet once daily · Considered off-label for acne; use when other treatments have failed.
Dysmenorrhoeaoff-label
Off-label use for primary dysmenorrhoea.
- adult · PO: 1 tablet once daily · Off-label use for primary dysmenorrhoea.
Contraindications & precautions
- Pregnancy
- Venous thromboembolism (current or history) · Includes deep vein thrombosis, pulmonary embolism
- Arterial thromboembolism (current or history) · Includes myocardial infarction, stroke, transient ischaemic attack
- Severe hypertension (≥160/100 mmHg) · Uncontrolled hypertension
- Migraine with aura · Increased risk of stroke
- Breast cancer (current or history) · Hormone-sensitive malignancy
- Liver disease with impaired function · Includes acute hepatitis, cirrhosis
- Age ≥35 years with ≥15 cigarettes/day · Consider alternative contraception
- Take at the same time each day to maintain consistent hormone levels.
- Use additional contraception if vomiting or diarrhoea occurs within 2 hours of taking the pill.
- Seek urgent medical advice for symptoms of VTE (leg pain, swelling), cardiovascular events (chest pain, breathlessness), or neurological symptoms (severe headache, visual disturbance).
- Avoid smoking, especially if over 35 years of age, due to increased cardiovascular risk.
- Inform the prescriber of any new medications, particularly enzyme inducers (e.g., rifampicin, phenytoin), which may reduce contraceptive efficacy.
- Monitor blood pressure regularly, especially in the first months of use.
Adverse effects
- Nausea
- Breast tenderness
- Headache
- Irregular bleeding (spotting)
- Mood changes
- Weight gain
- Acne
- Deep vein thrombosisserious
- Strokeserious
- Hepatic adenomaserious
Interactions
- carbamazepinemajorAvoid co-prescribing carbamazepine and combined oral contraceptives. If concurrent use is necessary, use an alternative contraceptive method such as a copper intrauterine device or a barrier method. Consider a progestogen-only method not reliant on CYP3A4, or a higher-dose combined pill, but no method is fully reliable. Counsel on breakthrough bleeding and the need for additional contraception during and for at least 28 days after stopping carbamazepine. Monitor for pregnancy.
- rifampicinmajorAvoid co-prescription where possible. If rifampicin is essential, advise a non-hormonal contraceptive method or an alternative contraception (e.g., barrier method or copper intrauterine device) for the entire duration of rifampicin therapy and for at least 28 days after stopping. Monitor for breakthrough bleeding and arrange pregnancy testing if appropriate.
Renal & hepatic adjustment
- Hepatic impairment (mild): No dose adjustment required. Monitor liver function tests.
- Hepatic impairment (moderate): Use with caution. Consider alternative contraception if hepatic impairment is significant.
- Hepatic impairment (severe): Contraindicated due to risk of adverse effects on liver function and potential for hepatic tumours. (avoid)
Monitoring, pregnancy & toxicity
- Blood pressure · At baseline, then every 6-12 months
- Liver function tests · If symptoms of liver dysfunction occur
- Signs of thromboembolism · At each review
- Pregnancy: Contraindicated in pregnancy. Discontinue immediately if pregnancy is suspected.
- Toxicity: Symptoms include nausea, vomiting, and withdrawal bleeding. · Treatment is supportive; no specific antidote. Large doses may require observation.
Clinical notes
Common side effects include nausea, breast tenderness, headache, and breakthrough bleeding. Serious risks include venous thromboembolism, particularly in smokers and women over 35. Contraindications include history of thrombosis, liver disease, and known sex-steroid sensitive malignancies. Interactions with enzyme-inducing drugs such as rifampicin and carbamazepine can reduce efficacy. Counsel patients that irregular bleeding is common in the first 3 months. Also note that it can be used for acne and menstrual cycle regulation, but prescribe according to local guidelines.
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BNF; local formulary