Ethinylestradiol + Levonorgestrel

Indications

Ethinylestradiol + Levonorgestrel is used for: Contraception

Adult Dose

Contraception Monophasic 1 active tablet PO daily for 21 days, then 1 inert (iron) tablet PO daily for 7 days Missed Active Contraceptive Dose One active tablet missed Take 1 tablet as soon as possible, or take 2 tablets on following day Alternatively, take 1 tablet, discard missed tablet, and continue taking subsequent tablets as scheduled Use other forms of contraception for next 7 days after missed dose or until menses occur Two active tablets missed consecutively Take 2 tablets as soon as remembered and continue taking as scheduled Alternatively, take 2 tablets daily for the next 2 days and continue taking as scheduled Missed 3rd week of cycle and patient is Sunday Starter: Take 1 pill every day until Sunday; discard rest of pack, and start new pack that same day Missed 3rd week of cycle and patient is day-1 starter: Discard rest of pack, and start new pack that same day Use other forms of contraception for next 7 days after missed dose or until menses occur Menses may not occur this month; if menses do not occur for 2 consecutive months, contact healthcare provider about possibility of pregnancy Three active tablets missed consecutively Sunday starter: Take 1 pill every day until Sunday; discard rest of pack, and start new pack that same day Day-1 starter: Discard rest of pack, and start new pack that same day Use other forms of contraception for next 7 days after missed dose or until menses occur Menses may not occur this month; if menses do not occur for 2 consecutive months, contact healthcare provider about possibility of pregnancy Dosing Considerations Post pregnancy After vaginal birth: Wait >3 weeks before initiating oral contraception After cesarean section birth: Wait >6 weeks before initiating oral contraception Women with other risk factors for VTE in addition to postpartum: Do not use combined hormonal contraceptives Presence of other VTE risk factors in addition to postpartum status: Do not use combined hormonal contraceptives Hepatic impairment: Do not administer

Child Dose

Renal Dose

Renal impairment: Use with caution

Administration

Contra Indications

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.

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. Lactation: Small amounts of steroids are excreted in breast milk; estrogens may reduce quality or quantity of milk; use of other forms of birth control may be advisable until infant is fully weaned (American Academy of Pediatrics committee states that formulation is compatible with nursing)

Pregnancy-Lactation

Pregnancy Contraindicated in pregnancy because there is no reason to use combined hormonal contraceptives (CHCs) in pregnancy Epidemiologic studies and meta-analyses have not found an increased risk of genital or nongenital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to CHCs before conception or during early pregnancy Lactation Combined hormonal contraceptives (CHCs) and/or metabolites are present in human milk and in breastfed infants CHCs, including levonorgestrel oral/ethinylestradiol/ferrous bisglycinate, can reduce milk production in breastfeeding females; reduction can occur at any time but is less likely to occur once breastfeeding Advise nursing female to use other methods of contraception until she discontinues breastfeeding

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.

Adverse Effects

Side effects of Ethinylestradiol + Levonorgestrel : 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.

Mechanism of Action

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.