MEGESTROL Drug Interactions: What You Need to Know

DRUG INTERACTIONS Pharmacokinetic studies show that there are no significant alterations in pharmacokinetic parameters of zidovudine or rifabutin to warrant dosage adjustment when megestrol acetate is administered with these drugs. The effects of zidovudine or rifabutin on the pharmacokinetics of megestrol acetate were not studied. Megestrol acetate may interact with warfarin and increase International Normalized Ratio (INR). Closely monitor INR in patients taking megestrol acetate and warfarin.

Animal Toxicology

Long-term treatment with megestrol acetate may increase the risk of respiratory infections. A trend toward increased frequency of respiratory infections, decreased lymphocyte counts, and increased neutrophil counts was observed in a two-year chronic toxicity/carcinogenicity study of megestrol acetate conducted in rats.

4 CONTRAINDICATIONS

• History of hypersensitivity to megestrol acetate or any component of the formulation.
• Pregnancy [see Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.1 , 8.3 )].
• History of hypersensitivity to megestrol acetate or any component of the formulation ( 4 ).
• Pregnancy ( 4 )( 8.1 ).

AND PRECAUTIONS

• Use with caution in patients with a history of thromboembolic disease (5.1) .
• Fetal Effects: May cause fetal harm. Females of reproductive potential should be advised to avoid becoming pregnant ( 5.2 ).
• Clinical cases of overt Cushing's Syndrome have been reported in association with the chronic use of megestrol acetate. In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic megestrol acetate in the stressed and non-stressed state (5.3) .
• New onset and exacerbation of pre-existing diabetes have been reported (5.4) .

5.1 General

• Effects on HIV viral replication have not been determined.
• Use with caution in patients with a history of thromboembolic disease.

5.2 Fetal Toxicity Based on animal studies, megestrol acetate may cause fetal harm when administered to a pregnant woman. Pregnant rats treated with low doses of megestrol acetate resulted in a reduction in fetal weight and number of live births, and feminization of male fetuses. There are no available human data to assess for any drug associated risks of miscarriage, birth defects, or adverse maternal or fetal outcomes. If this drug is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this drug, advise the patient of the poten ‑ tial hazard to the fetus <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.1 ), Nonclinical Toxicology ( 13.1 )]</span>. Obtain a pregnancy test in females of reproductive potential prior to initiating treatment with megestrol acetate oral suspension <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.1 )]</span>. Advise females of reproductive potential to use effective contraception while taking megestrol acetate oral suspension <span class="opacity-50 text-xs">[see Use in Specific Populations ( 8.3 )]</span>.

5.3 Adrenal Insufficiency The glucocorticoid activity of megestrol acetate oral suspension has not been fully evaluated. Clinical cases of overt Cushing&apos;s Syndrome have been reported in association with the chronic use of megestrol acetate. In addition, clinical cases of adrenal insufficiency have been observed in patients receiving or being withdrawn from chronic megestrol acetate therapy in the stressed and non-stressed state. Furthermore, adrenocorticotropin (ACTH) stimulation testing has revealed the frequent occurrence of asymptomatic pituitary-adrenal suppression in patients treated with chronic megestrol acetate therapy. Therefore, the possibility of adrenal insufficiency should be considered in any patient receiving or being withdrawn from chronic megestrol acetate oral suspension therapy who presents with symptoms and/or signs suggestive of hypoadrenalism (e.g., hypotension, nausea, vomiting, dizziness, or weakness) in either the stressed or non-stressed state. Laboratory evaluation for adrenal insufficiency and consideration of replacement or stress doses of a rapidly acting glucocorticoid are strongly recommended in such patients. Failure to recognize inhibition of the hypothalamic-pituitary adrenal axis may result in death. Finally, in patients who are receiving or being withdrawn from chronic megestrol acetate oral suspension therapy, consideration should be given to the use of empiric therapy with stress doses of a rapidly acting glucocorticoid during stress or serious intercurrent illness (e.g., surgery, infection).

5.4 Diabetes Clinical cases of new onset diabetes mellitus and exacerbation of pre-existing diabetes mellitus have been reported in association with the chronic use of megestrol acetate.