Progestogen (breast/endometrial cancer)
Megestrol is a progestogen used in hormone-dependent breast and endometrial cancer and, in another indication, to stimulate appetite and weight in patients with cachexia (severe weight loss). As a hormone, it blocks the hormonal environment that feeds certain tumours. It may cause vaginal bleeding and fluid retention; it is contraindicated in pregnancy.
Also known as: Megestrol, Megace
Megestrol + warfarin: megestrol may increase INR — monitor anticoagulation closely.
The megestrol label is explicit: "Megestrol acetate may interact with warfarin and increase International Normalized Ratio (INR). Closely monitor INR in patients taking megestrol acetate and warfarin". The mechanism is not fully established, but the effect on INR may be clinically relevant, especially in oncology patients with cachexia whose nutritional status is already unstable. When starting, adjusting or stopping megestrol, monitor INR more frequently and adjust the warfarin dose to target. Instruct the patient to report bleeding signs (gums, epistaxis, bruising, dark stools) and to avoid NSAIDs or other anticoagulants without supervision.
Megestrol + warfarin: monitor INR closely — megestrol may raise INR and bleeding risk.
The FDA label explicitly documents: "Megestrol acetate may interact with warfarin and increase International Normalized Ratio (INR). Closely monitor INR in patients taking megestrol acetate and warfarin".
Frequent INR during the combination and after any megestrol dose change.
Signs of bleeding (gums, epistaxis, bruising, dark stools) or INR above target.
Closely monitor INR when starting, adjusting or stopping megestrol in anticoagulated patients; adjust warfarin dose as needed.
DailyMed/FDA (NIH/NLM) — approved Megestrol label (Natco): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=582cff8a-1def-43d6-ba7e-dce49e3e9f27 ; approved Warfarin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=541c9a70-adaf-4ef3-94ba-ad4e70dfa057
Megestrol + rifampicin: rifampicin (CYP3A4 inducer) may reduce the effect of megestrol.
Like other progestogens, megestrol is metabolised by hydroxylation via CYP3A4, and the Prontuário records for the class "Rifampicin: reduction of effect". Rifampicin, a potent CYP3A4 inducer, reduces exposure to megestrol and may compromise the palliative hormonal effect in breast or endometrial cancer (and the orexigenic effect in cachexia). The combination is particularly relevant in oncology patients receiving tuberculosis treatment. Monitor clinical response (oncological control and nutritional status) and consider an alternative or adjustment when the combination is unavoidable.
Megestrol + rifampicin: monitor hormonal response — rifampicin may reduce the effect of megestrol.
Like other progestogens, megestrol is metabolised via CYP3A4; rifampicin, a potent inducer, accelerates metabolism and reduces exposure. The Prontuário documents for the class: "Interactions: typical of progestogens... Rifampicin: reduction of effect".
Periodic clinical assessment of response during the combination.
Loss of disease control during concomitant rifampicin use.
Monitor clinical response to hormonal therapy during rifampicin combination.
DailyMed/FDA (NIH/NLM) — approved Megestrol label (Natco): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=582cff8a-1def-43d6-ba7e-dce49e3e9f27 ; approved Rifampicin label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b389b1a3-672f-47e3-916c-4a9c044b211b ; Prontuário Terapêutico do INFARMED (11th ed., 2012) — Megestrol, 16.2.1.3
High-fat meals may increase oral absorption of megestrol (liposolubility) — effect not clinically quantified.
Take with meals, especially in cachexia where the goal is caloric intake.
DailyMed/FDA (NIH/NLM) — approved Megestrol label (Natco): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=582cff8a-1def-43d6-ba7e-dce49e3e9f27
Alcohol may worsen the gastrointestinal effects and drowsiness associated with megestrol.
Limit alcohol intake during treatment.
DailyMed/FDA (NIH/NLM) — approved Megestrol label (Natco): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=582cff8a-1def-43d6-ba7e-dce49e3e9f27
May cause fetal harm ("Megestrol acetate may cause fetal harm when administered to a pregnant woman" — label); formal contraindication.
Contraindicated in pregnancy; exclude pregnancy before starting.
DailyMed/FDA (NIH/NLM) — approved Megestrol label (Natco): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=582cff8a-1def-43d6-ba7e-dce49e3e9f27
Megestrol may cause hyperglycaemia and worsening of glycaemic control (label) — monitor in diabetics.
Monitor blood glucose in diabetic patients and adjust antidiabetic medication as needed.
DailyMed/FDA (NIH/NLM) — approved Megestrol label (Natco): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=582cff8a-1def-43d6-ba7e-dce49e3e9f27
May cause fetal harm ("Megestrol acetate may cause fetal harm when administered to a pregnant woman" — label).
Contraindicated in any trimester.
Insufficient data during lactation — avoid breastfeeding during treatment.
Exclude pregnancy before starting and use effective contraception during treatment.
DailyMed/FDA (NIH/NLM) — approved Megestrol label (Natco): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=582cff8a-1def-43d6-ba7e-dce49e3e9f27
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Progestogen with an antioestrogenic effect in hormone-dependent cancer and an orexigenic effect (increased appetite and weight) in cachexia; the orexigenic mechanism is not fully established.
Inhibition of gonadotrophin secretion and direct effect on hormone-dependent tumour cells (similar to medroxyprogesterone); the appetite effect appears to involve modulation of cytokines and neuropeptide Y, without a fully established mechanism.
Good oral absorption; exposure is sufficient for clinical effect in the oncology and cachexia indications.
Metabolised in the liver, mainly via CYP3A4, with formation of metabolites and renal and faecal elimination.
Elimination half-life of about 13–34 hours (dose-dependent), allowing once-daily administration.
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
