Interactions
Interactions of MGA include significantly decreased exposure to indinavir, which may necessitate an increased dosage of the medication. When MGA is co-administered with zidovudine and rifabutin, there is no significant change in exposure to these medications and no dosage adjustment is necessary. Pharmacology
Pharmacodynamics
MGA has progestogenic activity, antigonadotropic effects, weak partial androgenic activity, and weak glucocorticoid activity. Progestogenic activity
MGA is a progestogen, or an agonist of the progesterone receptor (PR). It has about 65% of the affinity of promegestone and 130% of the affinity of progesterone for the PR. Like other progestogens, MGA has functional antiestrogenic effects in certain tissues such as the endometrium and has antigonadotropic effects. The total endometrial transformation dose of MGA is 50 mg per cycle. Antigonadotropic and anticorticotropic effects
MGA has antigonadotropic effects in humans at sufficient doses, capable of profoundly suppressing circulating androgen and estrogen concentrations. The antigonadotropic effects of MGA are the result of activation of the PR, which suppresses the secretion of the gonadotropins—peptide hormones responsible for signaling the body to produce not only progesterone but also the androgens and the estrogens—from the pituitary gland as a form of negative feedback inhibition, and hence downregulates the hypothalamic–pituitary–gonadal axis (HPG axis), resulting in decreased levels of the sex hormones and interference with fertility. As such, MGA has functional antiandrogenic and antiestrogenic effects as well as contraceptive effects via its antigonadotropic effects.The precise ovulation-inhibiting dosage of MGA is unknown.
The optimal dosage with maximum effect for appetite stimulation has been determined to be 800 mg/day. The recommended oral dosage of MGA for breast cancer is 40 mg four times per day (160 mg/day total), while the medication is used at an oral dosage of 40 to 320 mg/day in divided doses for endometrial cancer. It has been used at far lower dosages (e.g., 1–5 mg/day oral, 25 mg/month i.m.) in combination with an estrogen for contraceptive purposes. Available forms
MGA is available as 5 mg, 20 mg, and 40 mg oral tablets and in oral suspensions of 40 mg/mL, 125 mg/mL, 625 mg/5 mL, and 820 mg/20 mL. It was used at doses of 1 mg, 2 mg, 4 mg, and 5 mg in combined oral contraceptives. MGA is formulated at a dose of 25 mg in combination with a dose of 3.75 mg estradiol in a microcrystalline aqueous suspension for use as a once-monthly combined injectable contraceptive in women. Contraindications
Contraindications of MGA include hypersensitivity to MGA or any component of its formulation, known or suspected pregnancy, and breastfeeding. MGA is a teratogen in animals and may have the potential to cause fetal harm, such as decreased fetal weight and feminization of male fetuses. Side effects
The most common side effect of MGA is weight gain, with an incidence of 15 to 70% at the high dosages used to treat breast cancer. Other side effects include vaginal bleeding (7–8%), nausea (7%), and edema (5%), as well as others such as dizziness and shortness of breath.