Methyldopa

Contraindications

Active liver disease, liver disorders associated with previous methyldopa treatment

Hypersensitivity to methyldopa or other ingredients (eg, sulfites)

Pheochromocytoma

Concomitant MAOIs

Cautions

CHF, dialysis patients (increased risk of hypertension following procedure), edema, hemolytic anemia, hypotension, severe bilateral CVD, history of liver disease

Avoid abrupt withdrawal

Risk of decreased libido and impotence in men

May impair ability to perform hazardous tasks

Tolerance develops on prolonged treatment, especially if no concurrent diuretic (methyldopa causes Na and water retention)

Interferes with some lab tests

IM/SC NOT recommended due to erratic absorption

Mechanism of Action

Methyldopa may lower blood pressure by stimulating central inhibitory alpha-adrenergic receptors, false neurotransmission, and/or reduction of plasma renin activity.

Pharmacokinetics

Onset: PO 3-6 hr; IV 4-6 hr

Duration: PO 12-24 hr; IV 10-16 hr

Absorption: 50%

Protein Bound: Minimal

Vd: 0.6 L/kg

Metabolism: Liver

Metabolite: Methyldopa-o-sulfate (may be active), 3-methoxy-methyldopa (inactive)

Excretion: Urine (70%), feces (30-50%)

Dialyzable: Yes (HD; removes 60%; PD removes lesser amount)

ALDOMET* (Methyldopa) is an antihypertensive drug.

Methyldopa, the L-isomer of alpha-methyldopa, is levo-3-(3,4-dihydroxyphenyl)-2-methylalanine. Its empirical formula is C10H13NO4, with a molecular weight of 211.22, and its structural formula is:

Methyldopa is a white to yellowish white, odorless fine powder, and is soluble in water.

ALDOMET (methyldopa) is supplied as tablets, for oral use, in three strengths: 125 mg, 250 mg, or 500 mg of methyldopa per tablet. Inactive ingredients in the tablets are: calcium disodium edetate, cellulose, citric acid, colloidal silicon dioxide, D&C Yellow 10, ethylcellulose, guar gum, hydroxypropyl methylcellulose, iron oxide, magnesium stearate, propylene glycol, talc, and titanium dioxide.

*Registered trademark of MERCK & CO., Inc., COPYRIGHT © MERCK & CO., Inc., 1985 All rights reserved

Methyldopa lowers blood pressure by decreasing the levels of certain chemicals in your blood. This allows your blood vessels (veins and arteries) to relax (widen) and your heart to beat more slowly and easily.

Methyldopa is used to treat hypertension (high blood pressure).

Methyldopa may also be used for purposes not listed in this medication guide.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Drinking alcohol can further lower your blood pressure and may increase certain side effects of methyldopa.

Tell your doctor about all other medicines you use, especially:

• ferrous gluconate, a type of iron (Ferate, Fergon);

• ferrous sulfate, a type of iron (Feosol, Fer-in-Sol, Feratab, and others);

• lithium (Eskalith, Lithobid); or

• any other blood pressure medications.

This list is not complete and other drugs may interact with methyldopa. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Absorption

Bioavailability

Generally about 50% of an oral dose is absorbed with peak plasma concentrations usually attained in approximately 3–6 hours.b

Onset

Following oral administration, maximum decrease in BP occurs in 4–6 hours.b c

Following IV administration, BP begins to decrease in 4–6 hours.b f

Duration

Following discontinuance of oral therapy, BP returns to pretreatment levels within 24–48 hours.c

Following IV administration, hypotensive effect lasts for 10–16 hours and hypertension recurs within 48 hours.b f

Distribution

Extent

Crosses the blood-brain barrier.h j

Methyldopa crosses the placenta in humans101 102 and is distributed into milk.101 103

Plasma Protein Binding

Weakly bound to plasma proteins.b

Elimination

Metabolism

Metabolized in the brain to α-methylnorepinephrine, the pharmacologically active metabolite.j n Other active metabolites include α-methylepinephrine and α-methyldopamine.k n

Extensively metabolized, probably in the GI tract and the liver, to sulfate conjugates.b c f

Elimination Route

49% of an IV dose is excreted in the urine (via glomerular filtration) as the parent drug and the sulfate conjugate.b f

70% of an oral dose is excreted in the urine as parent drug and metabolites.c

Unabsorbed methyldopa is excreted in the feces unchanged.b

Half-life

Plasma half-life is 105 or 90–127 minutes for methyldopa or methyldopate, respectively.d e f

Special Populations

In patients with renal impairment, renal clearance is decreased.b e

Removed by hemodialysis and peritoneal dialysis.b c

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as hydrochloride:

Generic: 250 mg/5 mL (5 mL)

Tablet, Oral:

Generic: 250 mg, 500 mg

Hypersensitivity to methyldopa or any component of the formulation; active hepatic disease (eg, acute hepatitis, active cirrhosis); hepatic disorders previously associated with use of methyldopa; concurrent use of MAO inhibitors

Injection: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Injectable dosage form is most stable at acid to neutral pH. Stability of parenteral admixture in D5W at room temperature (25°C) is 24 hours. Parenteral admixture is stable at room temperature for up to 125 hours (Newton 1981).

Tablets: Store at 20°C to 25°C (68°F to 77°F). Protect from light.

Concerns related to adverse effects:

• Edema: May produce clinical edema or weight gain; discontinue if edema worsens or signs of heart failure arise. Mild edema may be controlled with the concomitant use of diuretic therapy.

• Hematologic effects: Rare cases of reversible granulocytopenia and thrombocytopenia have been reported. May rarely produce hemolytic anemia; positive Coombs test occurs in 10% to 20% of patients usually occurring between 6 and 12 months of therapy; perform complete blood count (CBC) periodically. If methyldopa-induced Coombs-positive hemolytic anemia occurs during therapy, discontinue use and do not reinitiate; Coombs test may not revert back to normal for weeks to months following discontinuation.

• Hepatic effects: May rarely produce hepatic disorders including fatal hepatic necrosis. Discontinue use and do not reinitiate if fever, abnormal liver function tests, or jaundice is present.

• Sedation: Usually transient, sedation may occur with initiation or whenever the dose is increased.

Disease-related concerns:

• Cerebrovascular disease: Patients with severe bilateral cerebrovascular disease have exhibited involuntary choreoathetotic movements (rare); discontinue use if these symptoms develop.

• Hepatic impairment: Use with caution in patients with history of hepatic disease or impairment.

• Pheochromocytoma: Not recommended in patients with pheochromocytoma.

• Renal impairment: Use with caution in patients with renal impairment; may respond to smaller doses. The active metabolites of methyldopa accumulate in patients with renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Surgical patients: Patients on methyldopa may need less anesthetic agents (Miller 1968; Miller 2010).

Dosage form specific issues:

• Injection: Do not use injectable if bisulfite allergy.

Other warnings/precautions:

• Tolerance: May occur usually between the second and third month of therapy; adding a diuretic or increasing the dosage of methyldopa frequently restores blood pressure control.