MEGESTROL ACETATE
Chemistry - A synthetic progestin, megestrol acetate (MA) occurs as an essentially odorless, tasteless, white to creamy white, crystalline powder that is insoluble in water, sparingly soluble inalcohol, and slightly soluble in fixed oils. It has a melting range of 213°-219°C over a 3° range anda specific rotation of +8° to +12°.
Megestrol acetate is indicated in humans for the palliative treatment of advanced carcinoma of thebreast or endometrium.
The half-life of megestrol acetate is reported to be 8 days in the dog.
Contraindications/Precautions - Megestrol acetate is contraindicated in pregnant animals or inanimals with uterine disease, diabetes mellitus or mammary neoplasias. It has been recommendedthat MA not be used in dogs prior to their first estrous cycle or for anestrus therapy in dogs withabnormal cycles. The manufacturer (Schering) recommends that should estrus occur within 30 daysof cessation of MA therapy, mating be prevented.
For estrus control, the manufacturer recommends that drug must be given for the full treatmentregimen to be effective and that MA should not be given for more than two consecutive treatments.
In humans, megestrol acetate is to be used with caution in patients with thrombophlebitis and iscontraindicated as a test for pregnancy.
Cats may develop a transient diabetes mellitus while receiving MA. Polydipsia/polyuria, personalitychanges, increased weight, endometritis, cystic endometrial hyperplasia, mammary hypertrophy andneoplasias may also occur. Increased appetite and weight gain is not consistently seen, but MA isoccasionally used as an appetite stimulant. Rarely, megestrol acetate can cause hepatotoxicity incats.
Limited clinical studies have suggested that megestrol acetate may cause less cystic endometrialhyperplasia than other progestational agents, but cautious use and vigilant monitoring is still warranted.
In dogs, increased appetite and weight gain, lethargy, change in behavior or hair color, mucometra, endometritis, cystic endometrial hyperplasia, mammary enlargement and neoplasia, acromegaly, adrenocortical suppression or lactation (rare) may occur.
Overdosage/Toxicology Studies - No information was located regarding acute overdosage ofmegestrol acetate. In humans, dosages of up to 800 mg/day caused no observable adverse reactions.
Toxicity studies performed in dogs at dosages of 0.1 - 0.25 mg/kg/day PO for 36 months yieldedno gross abnormalities in the study population. Histologically, cystic endometrial hyperplasia wasnoted at 36 months, but resolved when therapy was discontinued. At dosages of 0.5 mg/kg/day POfor 5 months, a reversible uterine hyperplasia was seen in treated dogs. Dosages of 2 mg/kg/daydemonstrated early cystic endometritis in biopsies done on dogs at 64 days.
No effects were noted in either the bitch or litter when pregnant dogs received 0.25 mg/kg/day for32 days during the first half of pregnancy. Reduced litter sizes and puppy survival were detectedwhen the dose was given during the last half of pregnancy. Fetal hypospadias are possible ifprogestational agents are administered during pregnancy.
Concurrent corticosteroid use (long-term) may exacerbate adrenocortical suppression and diabetes mellitus.
Storage, Stability, Compatibility
Megestrol acetate tablets should be stored in well-closedcontainers at a temperature of less than 40°C. The tablets may be crushed and administered withfood. The veterinary manufacturer recommends storing the tablets from 2°-30°C (36°-86°F).Pharmacology - MEGESTROL ACETATE
Megestrol acetate possess the pharmacologic actions expected of the other progestationals discussed (e.g., medroxyprogesterone acetate). It has significant anti-estrogen andglucocorticoid activity (with resultant adrenal suppression). It does not have anabolic nor masculinizing effects on the developing fetus.Uses, Indications - Megestrol acetate (Ovaban®¯Schering) is approved by FDA for use in dogsonly for the postponement of estrus and the alleviation of false pregnancy in the dog. It is usedclinically in the United States and elsewhere for many dermatologic and behavior-related conditions, primarily in the cat. See the Dosage section for specific indications and dosages for both dogs andcats.Megestrol acetate is indicated in humans for the palliative treatment of advanced carcinoma of thebreast or endometrium.
Pharmacokinetics - MEGESTROL ACETATE
Megestrol acetate is well absorbed from the GI tract and appears to be metabolized completely in the liver to conjugates and free steroids.The half-life of megestrol acetate is reported to be 8 days in the dog.
Contraindications/Precautions - Megestrol acetate is contraindicated in pregnant animals or inanimals with uterine disease, diabetes mellitus or mammary neoplasias. It has been recommendedthat MA not be used in dogs prior to their first estrous cycle or for anestrus therapy in dogs withabnormal cycles. The manufacturer (Schering) recommends that should estrus occur within 30 daysof cessation of MA therapy, mating be prevented.
For estrus control, the manufacturer recommends that drug must be given for the full treatmentregimen to be effective and that MA should not be given for more than two consecutive treatments.
In humans, megestrol acetate is to be used with caution in patients with thrombophlebitis and iscontraindicated as a test for pregnancy.
Adverse Effects, Warnings
In cats, megestrol acetate can induce a profound adrenocorticalsuppression, adrenal atrophy, and an iatrogenic "Addison's" syndrome can develop at "standard"dosages (2.5 - 5.0 mg every other day) within 1 - 2 weeks. Once the drug has been discontinued, serum cortisol levels (both resting and ACTH-stimulated) will return to normal levels within a fewweeks. Clinical symptoms of adrenocortical insufficiency (e.g., vomiting, lethargy) are uncommon, but exogenous steroid support should be considered if the animal is stressed (surgery, trauma, etc.).Cats may develop a transient diabetes mellitus while receiving MA. Polydipsia/polyuria, personalitychanges, increased weight, endometritis, cystic endometrial hyperplasia, mammary hypertrophy andneoplasias may also occur. Increased appetite and weight gain is not consistently seen, but MA isoccasionally used as an appetite stimulant. Rarely, megestrol acetate can cause hepatotoxicity incats.
Limited clinical studies have suggested that megestrol acetate may cause less cystic endometrialhyperplasia than other progestational agents, but cautious use and vigilant monitoring is still warranted.
In dogs, increased appetite and weight gain, lethargy, change in behavior or hair color, mucometra, endometritis, cystic endometrial hyperplasia, mammary enlargement and neoplasia, acromegaly, adrenocortical suppression or lactation (rare) may occur.
Overdosage/Toxicology Studies - No information was located regarding acute overdosage ofmegestrol acetate. In humans, dosages of up to 800 mg/day caused no observable adverse reactions.
Toxicity studies performed in dogs at dosages of 0.1 - 0.25 mg/kg/day PO for 36 months yieldedno gross abnormalities in the study population. Histologically, cystic endometrial hyperplasia wasnoted at 36 months, but resolved when therapy was discontinued. At dosages of 0.5 mg/kg/day POfor 5 months, a reversible uterine hyperplasia was seen in treated dogs. Dosages of 2 mg/kg/daydemonstrated early cystic endometritis in biopsies done on dogs at 64 days.
No effects were noted in either the bitch or litter when pregnant dogs received 0.25 mg/kg/day for32 days during the first half of pregnancy. Reduced litter sizes and puppy survival were detectedwhen the dose was given during the last half of pregnancy. Fetal hypospadias are possible ifprogestational agents are administered during pregnancy.
Drug Interactions
None reported. A potential interaction exists with Rifampin, which maydecrease progestin activity if administered concomitantly. This is presumably due to microsomalenzyme induction with resultant increase in progestin metabolism. The clinical significance of thispotential interaction is unknown.Concurrent corticosteroid use (long-term) may exacerbate adrenocortical suppression and diabetes mellitus.