methyldopa

INDICATIONS & USAGE Hypertension.

DOSAGE & ADMINISTRATION Adults : Initiation of Therapy : The usual starting dosage of methyldopa tablets is 250 mg two to three times a day in the first 48 hours. The daily dosage then may be increased or decreased, preferably at intervals of not less than 2 days, until an adequate response is achieved. To minimize the sedation, start dosage increases in the evening. By adjustment of dosage, morning hypotension may be prevented without sacrificing control of afternoon blood pressure. When methyldopa tablets are given to patients on other antihypertensives, the dose of these agents may need to be adjusted to effect a smooth transition. When methyldopa tablets are given with anti-hypertensives other than thiazides, the initial dosage of methyldopa tablets should be limited to 500 mg daily in divided doses; when methyldopa tablets are added to a thiazide, the dosage of thiazide need not be changed. Maintenance of Therapy : The usual daily dosage of methyldopa tablets is 500 mg to 2 g in two to four doses. Although occasional patients have responded to higher doses, the maximum recommended daily dosage is 3 g. Once an effective dosage range is attained, a smooth blood pressure response occurs in most patients in 12 to 24 hours. Since methyldopa has a relatively short duration of action, withdrawal is followed by return of hypertension usually within 48 hours. This is not complicated by an overshoot of blood pressure. Occasionally tolerance may occur, usually between the second and third month of therapy. Adding a diuretic or increasing the dosage of methyldopa frequently will restore effective control of blood pressure. A thiazide may be added at any time during methyldopa therapy and is recommended if therapy has not been started with a thiazide or if effective control of blood pressure cannot be maintained on 2 g of methyldopa daily. Methyldopa is largely excreted by the kidney and patients with impaired renal function may respond to smaller doses. Syncope in older patients may be related to an increased sensitivity and advanced arteriosclerotic vascular disease. This may be avoided by lower doses. Pediatric Patients : Initial dosage is based on 10 mg/kg of body weight daily in two to four doses. The daily dosage then is increased or decreased until an adequate response is achieved. The maximum dosage is 65 mg/kg or 3 g daily, whichever is less. (See PRECAUTIONS: Pediatric Use .)

CONTRAINDICATIONS Methyldopa is contraindicated in patients: – with active hepatic disease, such as acute hepatitis and active cirrhosis. – with liver disorders previously associated with methyldopa therapy (see WARNINGS ). – with hypersensitivity to any component of this product. – on therapy with monoamine oxidase (MAO) inhibitors.

ADVERSE REACTIONS Sedation, usually transient, may occur during the initial period of therapy or whenever the dose is increased. Headache, asthenia, or weakness may be noted as early and transient symptoms. However, significant adverse effects due to methyldopa have been infrequent and this agent usually is well tolerated. The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity. Cardiovascular : Aggravation of angina pectoris, congestive heart failure, prolonged carotid sinus hypersensitivity, orthostatic hypotension (decrease daily dosage), edema or weight gain, bradycardia. Digestive : Pancreatitis, colitis, vomiting, diarrhea, sialadenitis, sore or “black” tongue, nausea, constipation, distension, flatus, dryness of mouth. Endocrine : Hyperprolactinemia. Hematologic : Bone marrow depression, leukopenia, granulocytopenia, thrombocytopenia, hemolytic anemia; positive tests for antinuclear antibody, LE cells, and rheumatoid factor, positive Coombs test. Hepatic : Liver disorders including hepatitis, jaundice, abnormal liver function tests (see WARNINGS ). Hypersensitivity : Myocarditis, pericarditis, vasculitis, lupus-like syndrome, drug-related fever, eosinophilia. Nervous System/Psychiatric : Parkinsonism, Bell’s palsy, decreased mental acuity, involuntary choreoathetotic movements, symptoms of cerebrovascular insufficiency, psychic disturbances including nightmares and reversible mild psychoses or depression, headache, sedation, asthenia or weakness, dizziness, light-headedness, paresthesias. Metabolic : Rise in BUN. Musculoskeletal : Arthralgia, with or without joint swelling; myalgia. Respiratory : Nasal stuffiness. Skin : Toxic epidermal necrolysis, rash. Urogenital : Amenorrhea, breast enlargement, gynecomastia, lactation, impotence, decreased libido. To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions When methyldopa is used with other antihypertensive drugs, potentiation of antihypertensive effect may occur. Patients should be followed carefully to detect side reactions or unusual manifestations of drug idiosyncrasy. Patients may require reduced doses of anesthetics when on methyldopa. If hypotension does occur during anesthesia, it usually can be controlled by vasopressors. The adrenergic receptors remain sensitive during treatment with methyldopa. When methyldopa and lithium are given concomitantly, the patient should be carefully monitored for symptoms of lithium toxicity. Read the circular for lithium preparations. Several studies demonstrate a decrease in the bioavailability of methyldopa when it is ingested with ferrous sulfate or ferrous gluconate. This may adversely affect blood pressure control in patients treated with methyldopa. Coadministration of methyldopa with ferrous sulfate or ferrous gluconate is not recommended. Monoamine oxidase (MAO) inhibitors: See CONTRAINDICATIONS .

DESCRIPTION Methyldopa is an antihypertensive and is the L-isomer of alpha-methyldopa. It is levo-3-(3,4-dihydroxyphenyl)-2-methylalanine sesquihydrate. Methyldopa is supplied as tablets for oral administration, containing 250 mg and 500 mg of methyldopa. The amount of methyldopa is calculated on the anhydrous basis. Its molecular formula is C 10 H 13 NO 4 •1 1/2 H 2 O, with a molecular weight of 238.24, and its structural formula is: Methyldopa is a white to yellowish white, odorless fine powder and is sparingly soluble in water. The tablets contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium lauryl sulfate, titanium dioxide, triacetin, FD&C yellow No. 6 aluminum lake and FD&C blue No. 2 aluminum lake. structure-methyldopa

OVERDOSAGE Acute overdosage may produce acute hypotension with other responses attributable to brain and gastrointestinal malfunction (excessive sedation, weakness, bradycardia, dizziness, light-headedness, constipation, distention, flatus, diarrhea, nausea, vomiting). In the event of overdosage, symptomatic and supportive measures should be employed. When ingestion is recent, gastric lavage or emesis may reduce absorption. When ingestion has been earlier, infusions may be helpful to promote urinary excretion. Otherwise, management includes special attention to cardiac rate and output, blood volume, electrolyte balance, paralytic ileus, urinary function and cerebral activity. Sympathomimetic drugs [e.g., levarterenol, epinephrine, ARAMINE ®† (Metaraminol Bitartrate)] may be indicated. Methyldopa is dialyzable. The oral LD 50 of methyldopa is greater than 1.5 g/kg in both the mouse and the rat.

HOW SUPPLIED Methyldopa Tablets, USP are supplied as film-coated tablets containing either 250 mg or 500 mg of Methyldopa, USP. The 250 mg tablet is a beige, film-coated, round, biconvex, beveled-edge tablet debossed with “RA04” on one side of the tablet and plain on the other side. They are available as follows: NDC 64980-571-01 bottles of 100 tablets The 500 mg tablet is a beige, film-coated, capsule-shaped, biconvex, beveled-edge tablet debossed with “RA05” on one side of the tablet and plain on the other side. They are available as follows: NDC 64980-572-01 bottles of 100 tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. † The brands listed are trademarks of their respective owners. Manufactured for : Rising Pharma Holdings, Inc. East Brunswick, NJ 08816 Issued : 08/2024 200722 PIR57250-01