Adult: Available preparation:
Norgestrel 0.3 mg and ethinylestradiol 0.03 mg tab
1 tab once daily, exactly as directed on the blister pack. Doses must be taken continuously at the same time each day. Refer to individual product guidelines on how to manage missed doses and for detailed dosing instructions.
High risk of arterial or venous thrombotic diseases such as coronary artery disease, cerebrovascular disease, current or history of DVT or pulmonary embolism, inherited or acquired hypercoagulopathies (e.g. protein C or S deficiency, factor V Leiden mutation, prothrombin mutation, antithrombin deficiency), thrombogenic valvular or rhythm diseases of the heart (e.g. subacute bacterial endocarditis with vascular disease, atrial fibrillation); diabetes mellitus with vascular disease, uncontrolled hypertension or hypertension with vascular disease; headaches with focal neurological symptoms, migraine with aura or migraine headaches in women aged >35 years, SLE with unknown or positive antiphospholipid antibodies, women aged >35 years who smoke. Current or history of breast cancer or other estrogen- or progestin-sensitive cancer (e.g. endometrial cancer), undiagnosed abnormal uterine bleeding, cholestatic jaundice of pregnancy, jaundice with prior combination hormonal contraceptive use, hepatic tumours (benign or malignant) or hepatic disease (e.g. acute viral hepatitis, severe [decompensated] cirrhosis). Pregnancy. Concomitant use with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.
Patient with a tendency to or history of chloasma gravidarum; current or family history of hypertriglyceridaemia, risk factors for CV disease (e.g. hypertension, high LDL, low HDL, smoking), diabetes or prediabetes, diseases which may be exacerbated by fluid retention; history of depression; hereditary angioedema, strong family history of breast cancer, breast nodules. Not indicated for use prior to menarche or in postmenopausal women. Not recommended for women with complicated organ transplants. Obese patient. Renal impairment. Lactation. Consider discontinuation at least 4 weeks before and 2 weeks after elective surgery associated with increased risk of thromboembolism and during or after periods of prolonged immobilisation.
Significant: Increased risk of breast and cervical cancer; chloasma; unscheduled (breakthrough or intracyclic) vaginal bleeding and spotting; amenorrhoea, oligomenorrhoea; cholestasis, gallbladder disease; changes in lipid levels (including serum triglycerides), decreased glucose tolerance, hypertension, fluid retention; increased thyroid-binding globulin, sex hormone-binding globulin and cortisol-binding globulin levels; retinal vascular thrombosis; depression; severe headache/migraine. Rarely, hepatocellular carcinoma (long-term use). Eye disorders: Steepening of corneal curvature, intolerance to contact lenses. Gastrointestinal disorders: Nausea, vomiting, abdominal pain or cramps, bloating. General disorders and administration site conditions: Fatigue. Investigations: Weight increase or decrease. Metabolism and nutrition disorders: Increased appetite. Nervous system disorders: Headache, nervousness. Reproductive system and breast disorders: Breast tenderness, enlargement, or secretion; cervical erosion, dysmenorrhoea, vaginal discharge, vaginal candidiasis. Skin and subcutaneous tissue disorders: Acne, rash. Vascular disorders: Aggravation of varicose veins. Potentially Fatal: Venous thromboembolism, arterial thrombosis (e.g. MI, stroke). Rarely, hepatic adenomas.
Assess pregnancy status prior to therapy and before initiating a new dosing cycle when 2 consecutive menstrual periods are missed. Monitor blood pressure (at baseline and yearly), lipid profile (in patients with hyperlipidaemias), glucose (in diabetic patients), and LFTs. Obtain weight at baseline (BMI at baseline may be helpful to monitor changes during therapy). Monitor signs and symptoms of depression, thromboembolic disorders, bleeding irregularities, and vision changes. Perform adequate diagnostic measures to rule out malignancy in all cases of undiagnosed abnormal vaginal bleeding.
Decreased serum concentration with CYP3A4 inducers (e.g. phenytoin, barbiturates, carbamazepine, topiramate, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, rifabutin, rufinamide, aprepitant, etravirine). Increased serum concentration with CYP3A4 inhibitors (e.g. itraconazole, ketoconazole).
Ethinylestradiol: May decrease the serum concentration of lamotrigine. May increase the serum concentration of ciclosporin, tizanidine, and theophylline. May diminish the therapeutic effect of thyroid products. Decreased exposure with colesevelam. Increased serum concentration when given with ascorbic acid. Potentially Fatal: Ethinylestradiol: Increased risk of ALT elevations when used concomitantly with combination drug regimen containing ombitasvir/paritaprevir/ritonavir, with or without dasabuvir.
Plasma levels may be decreased with St. John's wort. Increased plasma concentrations with grapefruit juice.
May interfere with the results of certain tests (e.g. lipids, glucose tolerance, coagulation factors, binding proteins).
Description: Norgestrel and ethinylestradiol suppress ovulation by negative feedback mechanism on the hypothalamus that changes the normal gonadotrophin secretion pattern of FSH and LH by the anterior pituitary gland, thereby blocking the follicular FSH phase and the midcycle surge of gonadotrophins. They also produce alterations in the genital tract and the tubal transport of the ova through the fallopian tubes. The changes in cervical mucus and the endometrium led to inhibition of sperm penetration into the uterus and an unfavourable environment for nidation, respectively.
Norgestrel is a 2nd generation synthetic progestin with moderate to high androgenic activity and minimal estrogenic activity. It is a racemic mixture of active and inactive enantiomers, of which, levonorgestrel is the active component.
Ethinylestradiol is a potent, synthetic estrogen with actions similar to estradiol. Pharmacokinetics: Absorption: Norgestrel: Readily absorbed from the gastrointestinal tract.
Ethinylestradiol: Rapidly and completely absorbed from the gastrointestinal tract. Bioavailability: 20-65%. Time to peak plasma concentration: 2-3 hours (initial); 12 hours (secondary). Distribution: Widely distributed. Enters breast milk (small amounts).
Norgestrel: Plasma protein binding: >90%, mainly to albumin and sex steroid-binding globulin.
Ethinylestradiol: Volume of distribution: 2.2-3.8 L/kg. Plasma protein binding: >90%, mainly to albumin. Metabolism: Norgestrel: Metabolised in the liver to form sulfate and glucuronide conjugates.
Ethinylestradiol: Metabolised in the liver via aromatic hydroxylation by CYP3A4 isoenzyme to form 2-hydroxyethinylestradiol and various conjugated metabolites; undergoes extensive enterohepatic recirculation. Excretion: Norgestrel: Mainly via urine; faeces (lesser extent). Elimination half-life: Approx 20 hours.
Ethinylestradiol: Via urine (60%) and faeces (40%) as metabolites. Elimination half-life: 5-30 hours.