Norgestimate

Oral
Atrophic vaginitis, Progestogen component in menopausal hormonal replacement therapy, Prophylaxis of osteoporosis

Oral
Part of combined oral contraceptive

Undiagnosed abnormal vaginal bleeding; history of or current thrombophlebitis or venous thromboembolic disorders; active or recent (within 1 year) arterial thromboembolic disease (e.g. stroke, MI); breast carcinoma, oestrogen-dependent tumour; hepatic impairment or disease; pregnancy.

Lactation. CV or renal impairment, DM, asthma, epilepsy and migraine. Conditions which may be made worse by fluid retention. Patients with a history of depression. Large doses should be used with caution in patients who are susceptible to thromboembolism. When used as a contraceptive, its efficacy may be compromised during episodes of vomiting or diarrhoea.

GI discomfort, changes in appetite or wt, fluid retention, oedema, acne, chloasma (melasma), allergic skin rashes, urticaria, mental depression, changes in libido, hair loss, hirsutism, fatigue, drowsiness or insomnia, fever, headache. May alter menstrual cycles. May alter serum lipid levels and LFTs.

Enzyme inducers e.g. carbamazepine, griseofulvin, phenobarbital, phenytoin, and rifampicin may increase clearance of progesterone and progestogens. Aminoglutethimide may reduce the serum levels of norgestimate. May inhibit ciclosporin metabolism. May also affect the efficacy of antidiabetic medications thus requiring a change in the antidiabetic dosage.

Description:
Mechanism of Action: Norgestimate is a progestogen that is structurally related to levonorgestrel. It binds to androgen and progestogen receptors but not oestrogen receptors. It counters oestrogenic effects by decreasing the number of nuclear oestradiol receptors and suppressing epithelial DNA synthesis in endometrial tissue. It is commonly used as the progestogenic component in combined oral contraceptives and menopausal HRT.
Pharmacokinetics:
Absorption: Largely metabolised in the GI/liver during 1st pass effect; its main active metabolite, 17-deacetylnorgestimate, reaches Cmax at approximately 2 hr after dose.
Distribution: Protein binding of 17-deacetylnorgestimate: Approximately 99%.
Excretion: Half-life of 17-deacetylnorgestimate: About 37 hr. Norgestimate metabolites are excreted via urine and faeces.

Oestrogens, Progesterones & Related Synthetic Drugs