Medroxyprogesterone/ Oestrogen

Registered South African indications:

• Menopause

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Known, suspected, or past cancer of the breast
• Known or suspected oestrogen-dependent neoplasia
• Known or suspected pregnancy
• Undiagnosed abnormal genital bleeding
• Active thrombophlebitis or thromboembolic disorders or a history of confirmed venous thromboembolism (e.g. deep venous thrombosis, pulmonary embolism)
• Active or recent arterial thromboembolic disease (e.g. stroke, myocardial infarction)
• Liver dysfunction or disease as long as liver function tests have failed to return to normal
• Porphyria

Cautions

• Breastfeeding
• Renal impairment
• Elderly
• Leiomyoma
• Endometriosis
• Risk factors for thromboembolic disorders
• Risk factors for oestrogen dependent tumours 
• Hypertension
• Diabetes mellitus
• Cholelithiasis
• Migraine or headaches
• Systemic lupus erythematosus
• History of endometrial hyperplasia
• Epilepsy
• Asthma
• Otosclerosis
• Cardiac impairment
• Pre-existing hypertriglyceridemia
• Thyroid dysfunction
• Severe hypocalcaemia
• Galactose intolerance
• Fructose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption 
• Sucrase-isomaltase insufficiency 

Forms avail. in SA and covered in this monograph: tab

Vasomotor symptoms- moderate to severe
- In women with intact uterus
Prevention and management of osteoporosis 
- In women with intact uterus
- Significant risk of osteoporosis when non-oestrogen medications are inappropriate
Atrophic vaginitis or urethrits 
- In women with intact uterus

Fixed dose combination
Medroxyprogesterone/ Oestrogen
2.5/0.625 (mg)
5/0.625 (mg)

• Oral (tab): 1 tab, dly

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A starting dose of 5mg of medroxyprogesterone acetate is appropriate for those patients in whom cycles without bleeding are to be achieved

Consider lowering the dose to the 2.5mg regimen after achieving amenorrhoea or within 12 months of initiating therapy

If bleeding occurs following the reduction of medroxyprogesterone acetate to 2.5mg, consider resuming the 5mg regimen

Not established for use in children

Pregnancy

• Contraindicated

Breastfeeding

• Caution; not recommended

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Contraindicated

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Depression
• Changes in libido
• Mood disturbances
• Irritability
• Dizziness
• Headache
• Migraine
• Anxiety
• Stroke
• Exacerbation of epilepsy
• Exacerbation of chorea

Cardiovascular Disorders

• Myocardial infarction
• Pulmonary embolism
• Superficial thrombophlebitis
• Increase in blood pressure

Respiratory Disorders

• Exacerbation of asthma

Gastrointestinal Disorders

• Nausea and vomiting
• Bloating
• Abdominal pain
• Pancreatitis

Hepatobiliary Disorders

• Gallbladder disease
• Cholestatic jaundice

Genitourinary Disorders

• Breast pain
• Breakthrough bleeding
• Dysmenorrhoea
• Breast tenderness
• Breast enlargement
• Nipple discharge
• Change in cervical ectropion and secretion
• Change in menstrual flow
• Galactorrhoea
• Increased size of uterine leiomyomata
• Vaginitis
• Vaginal candidiasis

Endocrine and Metabolic Disorders

• Glucose intolerance
• Exacerbation of porphyria
• Hypocalcaemia
• Changes in weight

Musculoskeletal Disorders

• Arthralgia
• Leg cramps

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Acne
• Pruritus
• Chloasma
• Melasma
• Hirsutism
• Rash
• Oedema

Immune, Blood and Lymphatic System Disorders

• Increased triglycerides
• Anaphylactic reactions
• Ribrocystic breast changes
• Ovarian cancer
• Enlargement of hepatic hemangiomas

Sensory Disorders

• Intolerance to contact lenses
• Retinal vascular thrombosis

• Anticonvulsants 
• Anti-infectives
• CYP450 inducers
• Ritonavir 
• Nelfinavir
• St John's wort 
• Metyrapone 
• Aminogluthimide 

• Breast examination
• Mammogram
• Papanicolaou smear

Specific cases may require

• Thyroid function
• Blood glucose
• Lipid profile
• Bone density scan
• Endometrial sampling
• Ophthalmic examination

Administration directions

• In women who are not taking hormone replacement therapy or women who switch from another continuous combined hormone replacement therapy product, treatment may be started on any convenient day
• In women transferring from a sequential hormone replacement therapy regimen, treatment should begin the day following completion of the prior regimen

Missed dose

• If a tablet is forgotten, it should be taken as soon as the patient remembers, therapy should then be continued as before
• If more than one tablet has been forgotten only the most recent tablet should be taken, the patient should not take double the usual dose to make up for missed tablets
• Missed pills may cause breakthrough bleeding

Medroxyprogesterone/ Oestrogen provides hormonal replacement therapy to alleviate some of the symptoms and/or conditions associated with oestrogen deficiency. Oestrogen replacement is provided by conjugated oestrogen and progestogen is supplied by medroxyprogesterone acetate in this combined tablet. The combined therapy of conjugated oestrogen and medroxyprogesterone acetate administered to postmenopausal women reduces the incidence of endometrial hyperplasia and hence may reduce the risk of endometrial carcinoma.

COMBINATION PREPARATIONS

Fixed combination preparations

Medroxyprogesterone/ Oestrogen

Tablet 2.5mg/0.625mg

• Premelle (Pfizer) originator (Discontinued 19 Oct 2018)

Tablet 5mg/0.625mg

• Premelle (Pfizer) originator (Discontinued 19 Oct 2018)