Levonorgestrel + Ethinylestradiol

Oral
Contraception

Use with caution and monitor BP.

Contraindicated.

Pregnancy, undiagnosed vaginal bleeding, severe arterial disease (or family history of atherogenic lipid profile); liver adenoma; porphyria; after evacuation of hydatidiform mole; history of breast cancer; hepatic impairment; thrombophloebitis or thromboembolic disorders; breast carcinoma except in selected patients being treated for metastatic disease; oestrogen-dependent tumour; smoking ≥40 cigarettes daily; >50 yr; diabetes complications present; BMI >39 kg/m²; migraine with typical focal aura, lasting >72 hr despite treatment or migraine treated with ergot derivatives; BP >160 mmHg systolic and 100 mmHg diastolic; transient ischaemic attacks without headaches; SLE; gallstones; history of haemolytic uraemic syndrome, pruritis during pregnancy; cholestatic jaundice; chorea or deterioration of otosclerosis pemphigoid; breast feeding during 1st 6 mth after delivery.

Sex-steroid dependent cancer; past ectopic pregnancy; malabsorption syndromes; functional ovarian cysts; active liver disease, recurrent cholestatic jaundice, history of jaundice in pregnancy; history of CV or renal impairment; DM; asthma; epilepsy; migraine; depression; lactation; conditions exacerbated by fluid retention; hypercalcaemia; CV and gall bladder diseases; lipid effects; familial defects of lipoprotein metabolism; patients at risk of venous thromboembolism, breast cancer, preexisting uterine leiomyomata and benign hepatic adenoma; family history of arterial disease in 1st degree relative <45 yr; BP > systolic 140 mmHg and diastolic 90 mmHg; >35 yr; BMI 30-39 kg/m²; migraine without focal aura, controlled with 5HT₁; GI upset (vomiting and diarrhoea), missed pills and interaction with other drugs may require additional contraceptive precautions. Should be taken at same time each day.

Menstrual irregularities; headache, dizziness; breast discomfort; gynaecomastia; depression; disturbance of appetite; wt changes; fluid retention; oedema; changes in libido; hair loss or hirsutism; GI disturbances (nausea and vomiting); genitourinary changes; haematologic disorders; endocrine and metabolic disorders; cholestatic jaundice; local skin reactions; chorea; contact lens intolerance; steeping of corneal curvature; pulmonary thromboembolism; carbohydrate and/or glucose intolerance; depression; chloasma; BP increase, liver impairment; reduced menstrual loss, 'spotting' in early cycles, absence of withdrawal bleeding; rarely photosensitivity; increased risk in breast cancer; elevation of plasma bound iodine, cortisol and thyroid binding, erythrocyte sedimentation may be accelerated; increases in plasma copper, iron and alkaline phosphatase; may affect serum triglyceride and lipoprotein levels; retinal vascular thrombosis.
Potentially Fatal: Hepatic tumours; increased risk of thromboembolism.

PO: X

Symptoms: nausea and vomiting, withdrawal bleeding may occur in females. Treatment: symptom specific and supportive; emesis and charcoal administration may be used.

CYP3A4 inducers may decrease levels/effects eg aminoglutethimide, carbamazepine, nafcillin, nevirapine, atazanavir, nelfinavir, phenobarbital, phenytoin, lamotrigine, rifamycins, griseofulvin and ritonavir; ampicillin, tetracycline and other antibiotics may reduce efficacy; oestrogens may antagonise anticoagulant effect of coumarins; may inhibit metabolism of prednisolone and ciclosporin; may reduce clearance of alprazolam, chlordiazepoxide, diazepam; may increase clearance of lorazepam, oxazepam, temazepam.

St John's Wort (Hypericum perforatum) may reduce levels and effect; avoid; alfalfa, black cohosh, bloodroot, hops, kudzu, licorice, red clover, saw palmetto, soybean, thyme, wild yam, yucca may have oestrogenic properties and increase the adverse and toxic effects; bloodroot, chasteberry, damiana, oregano, yucca have progestogenic properties and may increase the adverse and toxic effects; oral contraceptives may reduce metabolism and levels of cyanocobalamin, increased dietary intake or supplementation may be necessary; grapefruit juice antagonises metabolism.

Estradiol has reduced response to metyrapone test.

Description: Combination of hormonal contraceptives inhibits ovulation by modulating pituitary secretion of gonadotrophins, luteinising hormone and follicle stimulating hormone through a negative feedback system. They reduce sperm penetration if ovulation does occur by altering the cervical mucus; cause changes in the endometrium which reduce the risk of nidation and may change the tubal transport of the ova through the fallopian tubes.
Pharmacokinetics:
Absorption: Absorbed by GI tract. Bioavailability: ethinyl estradiol: 38-48%; levonorgestrel: 100%.
Distribution: Distribution: Ethinyl estradiol: 4.3 L/kg; Levonorgestrel: 1.8 L/kg. Protein binding: Ethinyl estradiol: 95-97%; Levonorgestrel: 97-99% bind to sex hormone-binding globulin and albumin.
Metabolism: Slowly metabolised. Estradiol: hepatic via oxidation and conjugation in GI tract; hydroxylated via CYP3A4 to metabolites; first-pass effect; enterohepatic recirculation; reversibly converted to estrone and estriol. Levonorgestrel: hepatic involving CYP3A4; undergoes reduction and conjugation followed by hydroxylation; forms metabolites.
Excretion: Half life elimination: estradiol: 12-23 hr; levonorgestrel: 22-49 hr. Excretion: levonorgestrel: urine (40-68% parent drug and metabolites) and faeces (16-48% as metabolites); estradiol: through urine as metabolites estrone and estriol, also through faeces in small quantities as glucuronide and sulphate conjugates.

Oral Contraceptives