Megestrol Acetate (megestrol acetate)

No dosing information is available for this tab.

Megestrol acetate is administered orally.

Megestrol acetate oral suspensions containing 200 mg/5 mL are not bioequivalent with the more concentrated oral suspension containing 625 mg/5 mL (Megace(R) ES). Threfore, the formulations are not interchangeable on a mg-per-mg basis. Patients receiving Megace(R) ES should be informed about the formulation differences to avoid overdosing or underdosing of the drug.

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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Megestrol/Dofetilide

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The active tubular secretion of dofetilide may be inhibited by megestrol.(1)

CLINICAL EFFECTS: The concurrent administration of dofetilide with megestrol may result in elevated levels and increased effects of dofetilide, including QT prolongation or torsades de pointes.(1)

PREDISPOSING FACTORS: Renal impairment may increase risk for excessive QTc prolongation as dofetilide is primarily renally eliminated. To prevent increased serum levels and risk for ventricular arrhythmias, dofetilide must be dose adjusted for creatinine clearance < or = to 60 mL/min.(1) The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2)

PATIENT MANAGEMENT: The manufacturer of dofetilide states that megestrol should not be used in patients on dofetilide. If dofetilide is to be discontinued, a washout of at least 2 days is recommended prior to starting megestrol.(1)

DISCUSSION: Dofetilide is primarily excreted in the urine via both glomerular filtration and active tubular secretion via the cation transport system. Megestrol is believed to inhibit the cation transport system. Other agents that inhibit this system, including cimetidine, ketoconazole, trimethoprim, and verapamil, have been shown to increase dofetilide levels. Therefore, the manufacturer of dofetilide states that megestrol should not be used in patients on dofetilide.(1)

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Medroxyprogesterone; Megestrol/Coumarin Anticoagulants

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The mechanism of this interaction is unknown but may involve inhibition of anticoagulant metabolism by medroxyprogesterone and megestrol.(1,2)

CLINICAL EFFECTS: The concurrent use of medroxyprogesterone or megestrol and coumarin anticoagulants may increase international normalized ratio (INR) and result in an increased risk for bleeding.(1,2)

PREDISPOSING FACTORS: The risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). Pharmacogenomic information: patients with a CYP2C9 intermediate metabolizer genotype, and/or 1-2 copies of a reduced function VKORC1 gene are expected to be more susceptible to this interaction. Although patients with a pre-existing CYP2C9 poor metabolizer genotype are expected to be less susceptible to effects from this drug combination, their reduced function genotypes (e.g. CYP2C9 *1/*3, *2/*2, *2/*3, and *3/*3) result in an inherently higher warfarin half-life and risk for warfarin-associated bleeding. CYP2C9 poor metabolizers generally require lower anticoagulant doses and more time (>2 to 4 weeks) to achieve to achieve effective and safe anticoagulation than patients without these CYP2C9 variants.

PATIENT MANAGEMENT: Patients receiving concurrent therapy with medroxyprogesterone or megestrol and a coumarin anticoagulant (e.g. warfarin) should have their INR closely monitored.(1) When concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin and/or hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. When applicable, perform agent-specific laboratory test (e.g. INR) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling.

DISCUSSION: A study of four patients on high-dose progestins (two patients on medroxyprogesterone 500 mg twice daily and two patients on megestrol 160 mg once daily) and warfarin found that the progestins decreased the clearance of warfarin by 34.8% (from 2.3 to 1.5 mL/h*kg BW) and increased the half-life of warfarin by 71.4% (from 43.4 to 74.4 hours).(2)

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• Lactation
• Pregnancy

• Adrenocortical insufficiency

• Chronic heart failure
• Diabetes mellitus
• Hypertension
• Thromboembolic disorder

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More Frequent

• Hypertension
• Skin rash

Less Frequent

• Anemia
• Bullous dermatitis

Rare or Very Rare

• Abnormal glucose tolerance
• Adrenocortical insufficiency
• Altered mental status
• Cardiomyopathy
• Chest pain
• Deep venous thrombosis
• Depression
• Diabetes mellitus
• Dyspnea
• Edema
• Hepatomegaly
• Hyperglycemia
• Leukopenia
• Peripheral edema
• Pulmonary thromboembolism
• Seizure disorder
• Thrombophlebitis
• Tumor flare reaction

More Frequent

• Diarrhea
• Erectile dysfunction
• Flatulence
• Insomnia
• Nausea
• Vomiting

Less Frequent

• Acute cognitive impairment
• Candidiasis
• Constipation
• Dyspepsia
• Fever
• General weakness
• Headache disorder
• Increased urinary frequency
• Infection
• Libido changes
• Sialorrhea
• Urinary tract infection
• Xerostomia

Rare or Very Rare

• Abnormal vaginal bleeding
• Acute abdominal pain
• Alopecia
• Cough
• Disturbance in thinking
• Gynecomastia
• Hyperhidrosis
• Hypoesthesia
• Pain
• Palpitations
• Paresthesia
• Peripheral sensory neuropathy
• Pharyngitis
• Pruritus of skin
• Toxic amblyopia
• Urinary incontinence

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No enhanced messaging available.

Although there are no adequate and controlled studies to date using megestrol acetate in pregnant women, the drug has been shown to produce fetal harm in rats. Administration of the drug to rats produced decreases in fetal weight and live births and feminization of male fetuses. No teratogenicity studies in animals have been performed using megestrol acetate dosages that are clinically relevant to humans. Although progestins have been used beginning in the first trimester of pregnancy to prevent habitual abortion, there is no adequate evidence from well-controlled studies to substantiate the efficacy of progestins for these uses during any phase of pregnancy; however, there is evidence of potential adverse effects on the fetus when these drugs are administered during pregnancy. In addition, in most women, the cause of abortion is a defective ovum, which progestins could not be expected to influence. Because of their uterine-relaxant effects, progestins may delay spontaneous abortion of fertilized defective ova. There is evidence of increased risk of hypospadias in male neonates associated with progestin use during pregnancy; however, there are insufficient data about the risk in female fetuses. Because of increased genital abnormalities caused by progestins in both male and female fetuses, the manufacturer states that megestrol acetate is not recommended during pregnancy. If a woman becomes pregnant while receiving megestrol acetate or is inadvertently exposed to the drug during pregnancy, she should notify her physician and should be advised of the potential risks to the fetus. Women of childbearing potential should be advised not to become pregnant while receiving megestrol acetate therapy, and they should be advised to use an effective form of contraception while receiving the drug.

The manufacturer states that because of the potential for serious adverse reactions to megestrol acetate in nursing infants, women receiving the drug should discontinue nursing.

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