Conjugated oestrogens + Medroxyprogesterone

Oral
Menopausal hormone replacement therapy

Oral
Menopausal vasomotor symptoms

Oral
Menopausal atrophic vaginitis

Oral
Prophylaxis of postmenopausal osteoporosis

Contraindicated.

Hypersensitivity to conjugated oestrogens or medroxyprogesterone. History, suspected or current breast cancer, oestrogen-dependent tumour (e.g. endometrial cancer) and thromboembolic disease (e.g. DVT, pulmonary embolism, stroke, MI). Undiagnosed genital bleeding, untreated endometrial hyperplasia, severe uncontrolled hypertension, thrombophilic disorders (e.g. protein C or S and antithrombin deficiency). Hepatic impairment. Pregnancy and lactation.

Patient with history of endometrial hyperplasia, risk factors for CV disorders (e.g. family history, obesity, hypercholesterolaemia, diabetes mellitus, hypertension, SLE), oestrogen-dependent tumour; hypertriglyceridaemia, hypoparathyroidism, otosclerosis, migraine, epilepsy, asthma, cholelithiasis, leiomyoma or endometriosis, bone cancer, porphyria, cardiac impairment; to undergo surgery. Renal impairment.

Significant: Increased risk of breast, endometrial and ovarian cancers, CV disorders (e.g. DVT, pulmonary embolism, stroke, MI), dementia, gallbladder disease; hypersensitivity reactions, retinal vascular thrombosis (manifested by partial or complete loss of vision, diplopia, proptosis, migraine), hypertension.
Cardiac disorders: Palpitation, chest pain.
Gastrointestinal disorders: Nausea, diarrhoea, dyspepsia, eructation, flatulence, abdominal pain.
General disorders and administration site conditions: Asthenia, back or pelvic pain.
Infections and infestations: Flu syndrome, moniliasis.
Investigations: Increased triglycerides, decreased glucose tolerance.
Metabolism and nutrition disorders: Weight gain/loss, increased appetite, oedema.
Musculoskeletal and connective tissue disorders: Leg cramp, arthralgia, hypertonia.
Nervous system disorders: Headache, migraine, dizziness.
Psychiatric disorders: Depression, emotional lability, nervousness, insomnia.
Renal and urinary disorder: Urinary incontinence.
Reproductive system and breast disorders: Breast pain, tenderness, enlargement or discharge; cervix disorder, menstrual disorder, metrorrhagia, menorrhagia, dysmenorrhoea, breakthrough bleeding or spotting, leucorrhoea, vaginitis.
Skin and subcutaneous tissue disorders: Acne, dry skin, diaphoresis, rash, pruritus.
Vascular disorders: Vasodilation.
Potentially Fatal: Anaphylaxis.

Assess personal and family medical history prior to start of treatment and at regular intervals thereafter. Include blood pressure, breast examinations (e.g. mammography) and Papanicolaou smear. Monitor for signs and symptoms of breast, endometrial and ovarian cancers and CV disorders. Periodically evaluate the need to continue treatment.

Symptoms: Nausea, vomiting, abdominal pain, drowsiness, fatigue, breast tenderness and withdrawal bleeding. Management: Symptomatic treatment.

Decreased effect with CYP enzyme system inducers (e.g. carbamazepine, phenobarbital, rifampicin). Increased adverse reactions with CYP enzyme system inhibitors (e.g. erythromycin, ketoconazole, ritonavir). May decrease effect of metyrapone. Conjugated oestrogens: Decrease the effect of thyroid hormone replacement therapy. Medroxyprogesterone: Decreased exposure with aminoglutethimide.

Decreased effect with St. John’s wort. Increased adverse reactions with grapefruit juice.

Decreased prothrombin time, partial thromboplastin time, platelet aggregation time. Increased platelet count. Increases thyroid-binding globulin, corticosteroid binding globulin and sex hormone-binding globulin.

Description:
Mechanism of Action: Conjugated oestrogens is a mixture of synthetic sex hormones including estrone sulfate, equilin sulfate, 17α-estradiol, 17α-dihydroequilin and 17β-dihydroequilin. During menopause, these hormones substitutes for oestrogen production and alleviates its symptoms. These hormones also prevent bone loss following menopause or ovariectomy. Medroxyprogesterone reduces the oestrogen-induced risk of endometrial hyperplasia in non-hysterectomised women.
Pharmacokinetics:
Absorption: Conjugated oestrogens: Well absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 7 hours (estrone). Medroxyprogesterone: Well absorbed from the gastrointestinal tract. Bioavailability: 0.6-10%. Time to peak plasma concentration: 2-4 hours.
Distribution: Conjugated oestrogens: Widely distributed. Mainly bound to sex hormone binding globulin and albumin. Medroxyprogesterone: Enters breast milk. Plasma protein binding: Approx 90%, mainly to albumin.
Metabolism: Conjugated oestrogens: Estradiol is metabolised in the liver by CYP enzyme system into estrone and estriol; estrone into estradiol and estriol; estriol into estradiol. Undergoes enterohepatic recycling via sulfate and glucuronide conjugation. Medroxyprogesterone: Extensively metabolised in the liver via hydroxylation and conjugation.
Excretion: Conjugated oestrogens: Via urine (mainly as estriol; as estradiol, estrone and conjugates). Elimination half-life: Approx 27 hours (estrone). Medroxyprogesterone: Via urine. Elimination half-life: Approx 16-30 hours.

Store between 20-25°C.

Oestrogens, Progesterones & Related Synthetic Drugs

G03FB06 - medroxyprogesterone and estrogen ; Belongs to the class of progestogens and estrogens in sequential preparations.
G03FA12 - medroxyprogesterone and estrogen ; Belongs to the class of progestogens and estrogens in fixed combinations.

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