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Drug Details
FARLUTAL
- Drug Class Description
Progestogens. - Generic Name
Medroxyprogesterone acetate - Presentation
Tablets - Description
Medroxyprogesterone acetate BP 100 mg, 250 mg and 500 mg respectively. - Indications
Palliative treatment of hormone-sensitive malignancies. Farlutal has been successfully used to produce regressions in breast, endometrial, prostatic and renal cell carcinoma. High dose Farlutal treatment has proved especially useful in breast carcinoma and in achieving subjective improvements in terminally ill patients, notably pain relief and improved performance status. - Adult Dosage
Route of administration: Oral
Adults and elderly
Suggested dosage schemes are as follows:-
Breast carcinoma
400 - 1500 mg daily is recommended, although doses of up to 2000 mg daily have been used. There is an alternative Farlutal formulation for injection. To be effective, daily oral administration must be at least 2-3 times the recommended i.m. dosage where the initial dose is 500-1000 mg/day i.m. for 4 weeks and maintenance dose 500 mg i.m. twice a week. The two treatment modalities, oral and i.m., may be mixed, especially in maintenance therapy to reduce the number of i.m. injections (and possible related adverse effects) and yet maintain high plasma levels with a minimum of oral therapy.
Other hormone dependent malignancies
The oral dose is 100-600 mg/day. For i.m. treatment of endometrial cancer the recommended initial dose is 400-1000 mg per week. If improvement is noted within a few weeks or months and the disease appears to be stabilised, it may be possible to maintain improvement with as little as 400 mg per month.
- Child Dosage
Not applicable. - Contra Indications
Medroxyprogesterone acetate is contraindicated in the following conditions:
• thrombophlebitis, thrombo-embolic disorders, and where there is a high risk of developing such manifestations [presence or history of atrial fibrillation, valvular disorders, endocarditis, heart failure, pulmonary embolism; thrombo-embolic ischaemic attack (TIA), cerebral infarction; atherosclerosis; immediate post surgery period]
• Previous idiopathic or current venous thromboembolism (deep vein thrombosis, pulmonary embolism)
• Active or recent arterial thrombo-embolic disease (e.g., angina, myocardial infarction)
• severe hepatic insufficiency
• hypercalcaemia in patients with osseous metastases
• suspected or early breast carcinoma
• missed abortion, metrorrhagia, known or suspected pregnancy
• undiagnosed vaginal bleeding
• known hypersensitivity to medroxyprogesterone acetate or any other component of Farlutal Tablets.
Progestogens are known to be porphyrogenic. Patients with a history of attacks or aged under 30 are at greatest risk of an acute attack while on progesterone treatment. A careful assessment of potential benefit should be made where this risk is present.
- Special Precautions
Warnings
Farlutal should be used under the direction of those experienced in cancer chemotherapy.
Since medroxyprogesterone acetate appears to enhance blood clotting potential, treatment should be discontinued upon the appearance of thrombo-embolic episodes, migraine or associated ocular problems such as sudden or partial or total loss of vision, diplopia or vascular lesions of the retina.
Treatment with medroxyprogesterone acetate should be discontinued in the event of:
• jaundice or deterioration in liver function
• significant increase in blood pressure
• new onset of migraine-type headache
In the event of vaginal bleeding occurring, an accurate diagnosis should be made. If a histological examination is indicated, the laboratory should be informed that the patient has been receiving a progestogen.
The pathologist or laboratory should be advised that the patient is receiving medroxyprogesterone acetate as this can decrease the levels of the following endocrine biomarkers:
• Plasma/urinary steroids (e.g., cortisol, oestrogen, pregnanediol, progesterone, testosterone)
• Plasma/urinary gonadotrophins (e.g., LH and FSH)
• Sex-hormone-binding-globulin
Precautions
Animal studies have shown that medroxyprogesterone acetate possesses adrenocorticoid activity and this effect has also been observed in humans. Patients treated with high doses continuously over long periods should be carefully observed for signs normally associated with adrenocorticoid therapy, such as hypertension, sodium retention, oedema, etc. Care is needed in treating patients with diabetes and/or arterial hypertension.
When used in oncology indications, medroxyprogesterone acetate may cause partial adrenal insufficiency (decrease in pituitary-adrenal axis response) during metyrapone testing. Thus the ability of the adrenal cortex to respond to ACTH should be demonstrated before metyrapone is administrated. The pathologist/laboratory should be made aware that the patient is being treated with medroxyprogesterone acetate.
Patients with the following conditions should be carefully monitored while taking progestogens:
• Conditions which may be influenced by potential fluid retention
o Epilepsy
o Migraine
o Asthma
o Cardiac dysfunction
o Renal dysfunction
• Hyperlipidaemia
• History of mental depression
• Diabetes (a decrease in glucose tolerance has been observed in some patients)
Farlutal may raise plasma calcium levels; some cases of hypercalcaemia have been reported in the treatment of breast carcinoma.
Risk of venous thromboembolism (VTE)
The risk of VTE has not been assessed for progesterone alone. However, VTE is a known risk factor of oestrogen-only and combined hormone replacement therapy. When prescribing medroxyprogesterone acetate for oncology indications the following precautions and risk factors should be considered in the light of the patient's condition, the dose of medroxyprogesterone acetate and the duration of therapy:
• Generally recognised risk factors for VTE include a personal or family history of VTE or known thrombo-embolic states, severe obesity (BMI> 30 kg/m2) and systemic lupus erythematosus
• The risk of VTE may be temporarily increased with prolonged immobilisation, major trauma or major surgery.
If VTE develops after initiating therapy, medroxyprogesterone acetate should be discontinued. Patients should be told to contact their doctor immediately if they become aware of a symptom suggestive of potential thromboembolism (e.g. painful swelling of a leg, sudden pain in the chest, dyspnoea).
- Interactions
Interaction with other medicaments
The metabolism of progestogens may be increased by concomitant administration of compounds known to induce drug-metabolising enzymes, specifically cytochrome P450 enzymes. These compounds include anticonvulsants (e.g., phenobarbital, phenytoin, carbamezapine) and anti-infectives (e.g., rifampicin, rifabutin, nevirapine, efavirenz).
Ritonavir and nelfinavir, although known as strong inhibitors, by contrast exhibit inducing properties when used concomitantly with steroid hormones. Herbal preparations containing St John's Wort (Hypericum Perforatum) may induce the metabolism of progestogens. Progestogen levels may therefore be reduced.
Aminoglutethimide has been reported to decrease plasma levels of some progestogens.
When used in combination with cytotoxic drugs, it is possible that progestogens may reduce the haematological toxicity of chemotherapy.
Special care should be taken when progestogens are administered with other drugs which also cause fluid retention, such as NSAIDs and vasodilators.
Progestogens may inhibit the metabolism of cyclosporin, leading to increased plasma cyclosporin concentrations.
Interactions with other medicinal treatments (including oral anti-coagulants) have rarely been reported, but causality has not been determined. The possibility of interaction should be born in mind in patients receiving concurrent treatment with other drugs.
Other forms of interaction
Progestogens can influence certain laboratory tests (e.g., tests for hepatic function, thyroid function and coagulation).
- Adverse Drug Reactions
Genitourinary Abnormal uterine bleeding (irregular, increase, decrease), amenorrhoea, alterations of cervical secretions, cervical erosions, prolonged anovulation Breast Galactorrhoea, mastodynia, tenderness Central Nervous System Confusion, depression, dizziness, euphoria, fatigue, headache, insomnia, loss of concentration, nervousness, somnolence, vision disorders Gastrointestinal/ Hepatobiliary Constipation, diarrhoea, dry mouth, disturbed liver function, jaundice, nausea, vomiting Metabolic & Nutritional Adrenergic-like effects (e.g., fine-hand tremors, sweating, cramps in calves at night), corticoid-like effects (e.g., facies lunaris, Cushingoid syndrome), decreased glucose tolerance, diabetic cataract, exacerbation of diabetes mellitus, glycosuria Cardiovascular Cerebral and myocardial infarction, congestive heart failure, increased blood pressure, palpitations, pulmonary embolism, retinal thrombosis, tachycardia, thrombo-embolic disorders, thrombophlebitis Haematological Elevation of white blood cells and platelet counts Skin & Mucous Membranes Acne, alopecia, hirsutism, pruritus, rash, urticaria Allergy Hypersensitivity reactions (e.g., anaphylaxis & anaphylactoid reactions, angioedema) Miscellaneous Changes in appetite, changes in libido, oedema/fluid retention, hypocalcaemia, malaise, pyrexia, weight change