Minoxidil

INDICATIONS AND USAGE Because of the potential for serious adverse effects, minoxidil tablets are indicated only in the treatment of hypertension that is symptomatic or associated with target organ damage and is not manageable with maximum therapeutic doses of a diuretic plus two other antihypertensive drugs. At the present time use in milder degrees of hypertension is not recommended because the benefit-risk relationship in such patients has not been defined. Minoxidil reduced supine diastolic blood pressure by 20 mm Hg or to 90 mm Hg or less in approximately 75% of patients, most of whom had hypertension that could not be controlled by other drugs.

DOSAGE AND ADMINISTRATION Patients over 12 years of age: The recommended initial dosage of minoxidil tablets is 5 mg given as a single daily dose. Daily dosage can be increased to 10 mg, 20 mg and then to 40 mg in single or divided doses if required for optimum blood pressure control. The effective dosage range is usually 10 mg to 40 mg per day. The maximum recommended dosage is 100 mg per day. Patients under 12 years of age: The initial dosage is 0.2 mg/kg minoxidil as a single daily dose. The dosage may be increased in 50 to 100% increments until optimum blood pressure control is achieved. The effective dosage range is usually 0.25 to 1.0 mg/kg/day. The maximum recommended dosage is 50 mg daily ( see 9 . Pediatric Use under PRECAUTIONS ). Dose frequency: The magnitude of within-day fluctuation of arterial pressure during therapy with minoxidil is directly proportional to the extent of pressure reduction. If supine diastolic pressure has been reduced less than 30 mmHg, the drug need be administered only once a day; if supine diastolic pressure has been reduced more than 30 mmHg, the daily dosage should be divided into two equal parts. Frequency of dosage adjustment: Dosage must be titrated carefully according to individual response. Intervals between dosage adjustments normally should be at least 3 days since the full response to a given dose is not obtained for at least that amount of time. Where a more rapid management of hypertension is required, dose adjustments can be made every 6 hours if the patient is carefully monitored. Concomitant therapy: Diuretic and beta-blocker or other sympathetic nervous system suppressant. Diuretics: Minoxidil must be used in conjunction with a diuretic in patients relying on renal function for maintaining salt and water balance. Diuretics have been used at the following dosages when starting therapy with minoxidil: hydrochlorothiazide (50 mg, b.i.d.) or other thiazides at equi-effective dosage; chlorthalidone (50 mg to 100 mg, once daily); furosemide (40 mg, b.i.d.). If excessive salt and water retention results in a weight gain of more than 5 pounds, diuretic therapy should be changed to furosemide; if the patient is already taking furosemide, dosage should be increased in accordance with the patient’s requirements. Beta-blocker or other sympathetic nervous system suppressants: When therapy with minoxidil is begun, the dosage of a beta-adrenergic receptor blocking drug should be the equivalent of 80 mg to 160 mg of propranolol per day in divided doses. If beta-blockers are contraindicated, methyldopa (250 mg to 750 mg, b.i.d.) may be used instead. Methyldopa must be given for at least 24 hours before starting therapy with minoxidil because of the delay in the onset of methyldopa’s action. Limited clinical experience indicates that clonidine may also be used to prevent tachycardia induced by minoxidil; the usual dosage is 0.1 mg to 0.2 mg twice daily. Sympathetic nervous system suppressants may not completely prevent an increase in heart rate due to minoxidil but usually do prevent tachycardia. Typically, patients receiving a beta-blocker prior to initiation of therapy with minoxidil have a bradycardia and can be expected to have an increase in heart rate toward normal when minoxidil is added. When treatment with minoxidil and beta-blocker or other sympathetic nervous system suppressant are begun simultaneously, their opposing cardiac effects usually nullify each other, leading to little change in heart rate.

CONTRAINDICATIONS Minoxidil tablets are contraindicated in pheochromocytoma, because it may stimulate secretion of catecholamines from the tumor through its antihypertensive action. Minoxidil tablets are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

ADVERSE REACTIONS 1. Salt and Water Retention (see WARNINGS: Concomitant Use of an Adequate Diuretic is Required)—Temporary edema developed in 7% of patients who were not edematous at the start of therapy. 2. Pericarditis, Pericardial Effusion, and Tamponade (see WARNINGS ). 3. Dermatologic —Hypertrichosis—Elongation, thickening, and enhanced pigmentation of fine body hair are seen in about 80% of patients taking minoxidil tablets. This develops within 3 to 6 weeks after starting therapy. It is usually first noticed on the temples, between the eyebrows, between the hairline and the eyebrows, or in the side-burn area of the upper lateral cheek, later extending to the back, arms, legs, and scalp. Upon discontinuation of minoxidil, new hair growth stops, but 1 to 6 months may be required for restoration to pretreatment appearance. No endocrine abnormalities have been found to explain the abnormal hair growth; thus, it is hypertrichosis without virilism. Hair growth is especially disturbing to children and women and such patients should be thoroughly informed about this effect before therapy with minoxidil is begun. Allergic—Rashes have been reported, including rare reports of bullous eruptions, toxic epidermal necrolysis, and Stevens-Johnson Syndrome. 4. Hematologic —Thrombocytopenia and leukopenia (WBC<3000/mm 3 ) have rarely been reported. 5. Gastrointestinal —Nausea and/or vomiting has been reported. In clinical trials the incidence of nausea and vomiting associated with the underlying disease has shown a decrease from pretrial levels. 6. Miscellaneous —Breast tenderness—This developed in less than 1% of patients. 7. Altered Laboratory Findings —(a) ECG changes—Changes in direction and magnitude of the ECG T-waves occur in approximately 60% of patients treated with minoxidil. In rare instances a large negative amplitude of the T-wave may encroach upon the S-T segment, but the S-T segment is not independently altered. These changes usually disappear with continuance of treatment and revert to the pretreatment state if minoxidil is discontinued. No symptoms have been associated with these changes, nor have there been alterations in blood cell counts or in plasma enzyme concentrations that would suggest myocardial damage. Long-term treatment of patients manifesting such changes has provided no evidence of deteriorating cardiac function. At present the changes appear to be nonspecific and without identifiable clinical significance. (b)—Effects of hemodilution—hematocrit, hemoglobin and erythrocyte count usually fall about 7% initially and then recover to pretreatment levels. (c) Other—Alkaline phosphatase increased varyingly without other evidence of liver or bone abnormality. Serum creatinine increased an average of 6% and BUN slightly more, but later declined to pretreatment levels. To report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-800-272-5525 or FDA at 1-800-FDA-1088 or Error! Hyperlink reference not valid. for voluntary reporting of adverse reactions.

4. Drug interactions See " Interaction with Guanethidine " under WARNINGS .

DESCRIPTION Minoxidil tablets, USP contain minoxidil, USP an antihypertensive peripheral vasodilator. Minoxidil occurs as a white to off-white, crystalline powder, soluble in alcohol and propylene glycol; sparingly soluble in methanol; slightly soluble in water; practically insoluble in chloroform, acetone and ethyl acetate. The chemical name for minoxidil, USP is 2,4-pyrimidinediamine,6-(1-piperidinyl)-, 3-oxide. The structural formula is represented below: C 9 H 15 N 5 O M.W. 209.25 Minoxidil tablets, USP for oral administration contain either 2.5 mg or 10 mg of minoxidil, USP. Minoxidil Tablets, USP 2.5 mg and 10 mg contain the following inactive ingredients: anhydrous lactose, docusate sodium, magnesium stearate, microcrystalline cellulose, sodium benzoate and sodium starch glycolate. Structural formula of minoxidil

OVERDOSAGE There have been only a few instances of deliberate or accidental overdosage with minoxidil tablets. One patient recovered after taking 50 mg of minoxidil together with 500 mg of a barbiturate. When exaggerated hypotension is encountered, it is most likely to occur in association with residual sympathetic nervous system blockade from previous therapy (guanethidine-like effects or alpha-adrenergic blockage), which prevents the usual compensatory maintenance of blood pressure. Intravenous administration of normal saline will help to maintain blood pressure and facilitate urine formation in these patients. Sympathomimetic drugs such as norepinephrine or epinephrine should be avoided because of their excessive cardiac stimulating action. Phenylephrine, angiotensin II, vasopressin, and dopamine all reverse hypotension due to minoxidil, but should only be used if underperfusion of a vital organ is evident. Radioimmunoassay can be performed to determine the concentration of minoxidil in the blood. At the maximum adult dose of 100 mg/day, peak blood levels of 1,641 ng/mL and 2,441 ng/mL were observed in two patients, respectively. Due to patient-to-patient variation in blood levels, it is difficult to establish an overdosage warning level. In general, a substantial increase above 2,000 ng/mL should be regarded as overdosage, unless the physician is aware that the patient has taken no more than the maximum dose. Oral LD 50 in rats has ranged from 1,321 – 3,492 mg/kg; in mice, 2,456 – 2,648 mg/kg.

HOW SUPPLIED Minoxidil Tablets, USP 2.5 mg are 9/32 ", scored, round, white tablets imprinted “ DAN 5642 ” and “ 2.5 ” supplied in bottles of 100 NDC 0591-5642-01 and 500 NDC 0591-5642-05. Minoxidil Tablets, USP 10 mg are 9/32 ", scored, round, white tablets imprinted “ DAN 5643 ” and “ 10 ” supplied in bottles of 100 NDC 0591-5643-01 and 500 NDC 0591-5643-05. Dispense in a tight container with child-resistant closure. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense with Patient Package Insert available at: www.tevausa.com/PatientPI Manufactured In India By: Watson Pharma Private Limited Verna, Salcette Goa 403 722, India Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Rev. B 2/2024