Medroxyprogesterone Acetate

Registered South African indications:

• Dysfunctional uterine bleeding
• Mild to moderate endometriosis
• Opposition of endometrial effects of oestrogen in menopausal women treated with oestrogen
• Alleviation of menopausal vasomotor symptoms
• Diagnostics in amenorrhoea
• Recurrent and/or metastatic endometrial cancer (100mg, 500mg tab)
• Recurrent and/or metastatic renal cancer (100mg, 500mg tab)
• Recurrent and/or metastatic breast cancer in post-menopausal women (100mg, 500mg tab)

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy (known or suspected)
• Hepatic impairment
• Porphyria
• Breast cancer (suspected or early breast carcinoma)
• Hypercalcaemia in patients with osseous metastases
• Missed abortion
• Metrorrhagia
• Undiagnosed vaginal bleeding
• Previous idiopathic or current venous thromboembolism
• Deep vein thrombosis
• Pulmonary embolism
• Active or recent arterial thromboembolic disease (e.g. angina, myocardial infarction)
• Thrombophlebitis or at high risk of
• Thromboembolic disorders or at high risk of
• Presence or history of atrial fibrillation
• Valvular disorders
• Endocarditis
• Heart failure
• Pulmonary embolism
• Thromboembolic ischaemic attack (TIA)
• Cerebral infarction
• Atherosclerosis
• Immediate post-surgery period

Cautions

• Breastfeeding
• Renal impairment
• Diabetes mellitus with or without vascular involvement
• Hypertension
• Liver disorders (e.g. liver adenoma)
• Epilepsy
• Asthma
• Cardiac dysfunction
• History of mental depression
• Cholelithiasis
• Hyperlipidaemia
• History of thromboembolic disorders
• Known thromboembolic states
• Personal or family history of VTE
• Severe obesity (BMI >30 kg/m²)
• Systemic lupus erythematosus
• Prolonged immobilisation
• Major trauma or major surgery
• Migraine or severe headache
• Prolonged use
• High doses
• Risk factors for oestrogen dependent tumours (e.g. 1 degree heredity for breast cancer)
• Otosclerosis
• Unexpected vaginal bleeding
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

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

Dysfunctional (anovulatory) uterine bleeding

• Oral (tab): 2.5-10mg, dly for 5-10 days starting any day between the 16th-21st day of the menstrual cycle; Treatment duration: Continue for 2 cycles

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If bleeding occurs from a poorly developed proliferative endometrium, conventional oestrogen therapy may be employed in conjunction with medroxyprogesterone acetate in doses of 5-10 mg for 10 days

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Secondary amenorrhoea

• Oral (tab): 2.5-10mg, dly for 5-10 days starting any day between the 16th-21st day of the menstrual cycle; Treatment duration: Repeat for 3 cycles

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If amenorrhoea associated with a poorly developed proliferative endometrium, conventional oestrogen therapy may be employed in conjunction with medroxyprogesterone acetate in doses of 5-10 mg for 10 days

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Endometriosis - mild to moderate

• Oral (tab): 10mg, 8hrly; Treatment duration: 90 days continuously

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Initiate on day 1 of the menstrual cycle (1st day of menstruation = 1st day of cycle)

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Breakthrough bleeding, which is self-limiting, may occur. No additional hormonal therapy is recommended for the management of this bleeding

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To oppose the endometrial effects of oestrogen in oestrogen-treated postmenopausal women

• Oral (tab): 5-10mg, dly beginning on the 16th day of a 25 day course of oestrogen therapy: Treatment duration: At least 10 days

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Progestin withdrawal bleeding should occur, beginning on the 3rd to 7th day post medroxyprogesterone acetate treatment

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Alleviation of menopausal vasomotor symptoms

• Oral (tab): 10-20mg, dly

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Primary amenorrhoea

• Oral (tab): 5-10mg, dly; Treatment duration: 10 days

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Progestin withdrawal bleeding should ensue within 3-7 days if the endometrium has been previously primed with adequate endogenous oestrogen

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Pregnancy must be excluded before administration of medroxyprogesterone acetate

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Advanced or metastatic endometrial cancer
Palliative treatment of
- Recurrent and/or metastatic endometrial cancer
- Recurrent and/or metastatic renal cancer
- Recurrent and/or metastatic breast cancer in post-menopausal women

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Consult specialist for dosages and regimens

Not indicated for use in children

Pregnancy

• Contraindicated
• Medroxyprogesterone acetate is contraindicated in women who are pregnant

• Some reports suggest an association between intrauterine exposure to progestational drugs in the first trimester of pregnancy and genital abnormalities in male and female foetuses. If medroxyprogesterone acetate is used during pregnancy, or if the patient becomes pregnant while using this drug, the patient should be apprised of the potential hazard to the foetus

  Infants from unintentional pregnancies that occur 1 to 2 months after injection of medroxyprogesterone acetate injectable suspension may be at an increased risk of low birth weight, which, in turn, is associated with an increased risk of neonatal death. The attributable risk is low because pregnancies while on medroxyprogesterone acetate are uncommon

Breastfeeding

• Caution
• Medroxyprogesterone acetate and its metabolites are secreted in breast milk
• In breastfeeding mothers treated with medroxyprogesterone acetate injection 150mg IM every 3 months, milk composition, quality, and amount are not adversely affected
• Neonates and infants exposed to MPA from breast milk have been studied for developmental and behavioural effects through puberty. No adverse effects have been noted
• However, due to limitations of the data regarding the effects of MPA in breastfed infants less than six weeks old, medroxyprogesterone acetate should be given no sooner than six weeks post-partum when the infant's enzyme system is more developed

Fertility

• Medroxyprogesterone acetate at oral doses may inhibit ovulation
• Women may experience a delay in return to fertility (conception) following discontinuation of medroxyprogesterone acetate

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Contraindicated

Elderly

• 5-10mg: Not indicated for use in geriatric patients
• 100-500mg: No dose adjustment recommended 

Porphyria Information

• Probably porphyrinogenic (PRP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Insomnia
• Depression
• Euphoria
• Changes in libido
• Nervousness
• Confusion
• Headache
• Dizziness
• Tremors
• Cerebral infarction
• Somnolence
• Loss of concentration
• Malaise

Cardiovascular Disorders

• Congestive heart failure
• Myocardial infarction
• Tachycardia
• Palpitations
• Thrombophlebitis
• Embolism
• Thrombosis
• Increased blood pressure
• Adrenergic-like effects
• Hypertension
• Oedema

Respiratory Disorders

• Pulmonary embolism

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Diarrhoea
• Dry mouth

Hepatobiliary Disorders

• Hepatobiliary disorders
• Abnormal hepatic function
• Abnormal liver function test
• Jaundice

Genitourinary Disorders

• Glycosuria
• Erectile dysfunction
• Dysfunctional uterine bleeding (irregular, increase, decrease, spotting)
• Breast pain
• Amenorrhoea
• Uterine cervical erosions
• Cervical discharge
• Galactorrhea

Endocrine and Metabolic Disorders

• Corticoid-like effects
• Prolonged anovulation
• Weight fluctuation
• Increased appetite
• Diabetes mellitus exacerbated
• Hypercalcaemia
• Decreased glucose tolerance
• Sodium retention

Musculoskeletal Disorders

• Muscle spasms

Skin and Subcutaneous Tissue Disorders

• Hyperhidrosis
• Acne
• Hirsutism
• Alopecia
• Rash
• Urticaria
• Pruritus

Immune, Blood and Lymphatic System Disorders

• Angioedema
• Hypersensitivity
• Anaphylactic reactions
• Anaphylactoid reaction
• Increased white blood cell count 
• Increased platelet count
• Fever

Sensory Disorders

• Retinal embolism and thrombosis
• Cataract
• Visual impairment
• Proptosis
• Diplopia
• Papilloedema
• Retinal vascular lesions

• CYP450 inducers
• Anticonvulsants
• Phenobarbital
• Phenytoin
• Carbamazepine
• Anti-infectives
• Rifampicin
• Rifabutin
• Nevirapine
• Efavirenz
• Ritonavir
• Nelfinavir
• Aminoglutethimide
• Ciclosporin
• Oral anticoagulants
• Agents which cause fluid retention
• Vasodilators
• Nonsteroidal anti-inflammatory drugs
• Cytotoxic agents
• St John's wort (Hypericum Perforatum)

None routine. Specific cases may require

• Hepatic function
• Mental status
• Ophthalmic examination
• Blood glucose level
• Blood pressure
• Pelvic examination

None routine. Specific cases may require

• Body mass index
• Bone mineral density
• Mammography
• Cervical cytology
• Pregnancy test
• Lipid profile

Medroxyprogesterone acetate (MPA) has actions and uses similar to those of progesterone. MPA has minimal androgenic activity compared to progesterone and virtually no oestrogenic activity. Progestogens are used in the treatment of dysfunctional uterine bleeding, secondary amenorrhoea and endometriosis.

Tablet 5mg

• Hexal-Mpa 5 (Sandoz)
• Provera (Pfizer) originator

Tablet 10mg

• Hexal-MPA 5 (Sandoz)
• Provera (Pfizer) originator

Tablet 100mg

• Provera (Pfizer) originator

Tablet 500mg

• Provera (Pfizer) originator

Also available in the following form: Injection.

COMBINATION PREPARATIONS

Conjugated oestragen/ Medroxyprogesterone

Tablet 0.625mg/2.5mg

• Premelle 2.5 (Pfizer) originator

Tablet 0.625mg/5mg

• Premelle 5 (Pfizer) originator

Tablet 0.625mg/2.5mg

• Premelle cycle-5 (Pfizer) originator

Medroxyprogesterone acetate/ Oestradiol valerate/ Oestradiol valerate/ Placebo

Tablet 20mg/2mg/2mg/86.5mg

• Trivina (Pharmacare)