Levonorgestrel + Ethinylestradiol


Concise Prescribing Info
Indications/Uses
Contraception.
Dosage/Direction for Use
Adult : PO Monophasic combined OC: As tab containing levonogestrel 150-250 mcg and ethinylestradiol 30 mcg: 1 tab once daily. Triphasic combined OC: Levonorgestrel 50-125 mcg + ethinylestradiol 30-40 mcg: 1 tab once daily.
Dosage Details
Oral
Contraception
Adult: Monophasic combined oral contraceptive (COC): levonorgestrel 150-250 mcg + ethinylestradiol 30 mcg once daily. Triphasic COC: levonorgestrel 50-125 mcg + ethinylestradiol 30-40 mcg once daily.
Renal Impairment
Use with caution and monitor BP.
Hepatic Impairment
Contraindicated.
Contraindications
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.
Special Precautions
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.
Adverse Reactions
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.
Overdosage
Symptoms: nausea and vomiting, withdrawal bleeding may occur in females. Treatment: symptom specific and supportive; emesis and charcoal administration may be used.
Drug Interactions
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.
Food Interaction
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.
Lab Interference
Estradiol has reduced response to metyrapone test.
Action
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.
MIMS Class
Disclaimer: This information is independently developed by MIMS based on Levonorgestrel + Ethinylestradiol from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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