METHYLDOPATE HYDROCHLORIDE

Clinical safety rating: safe

Lithium may cause increased lithium toxicity Can cause hemolytic anemia and positive Coombs test.

How it works

Methyldopate hydrochloride is a prodrug that is converted to alpha-methylnorepinephrine in the central nervous system, which stimulates central alpha-2 adrenergic receptors, reducing sympathetic outflow and decreasing peripheral vascular resistance, thereby lowering blood pressure.

What the body does with it

Metabolism	Hydrolyzed by esterases to methyldopa; methyldopa is metabolized primarily via sulfate conjugation (sulfotransferases) and to a lesser extent via O-methylation (catechol-O-methyltransferase) and renal excretion.
Excretion	Primarily renal excretion as sulfate conjugate (50-70%) and unchanged drug (20-30%); minimal biliary/fecal elimination (<5%).
Half-life	Terminal elimination half-life is 1.5-2 hours in normal renal function; clinically, due to prolonged pharmacodynamic effect, dosing is every 6-12 hours.
Protein binding	<15% bound to albumin.
Volume of Distribution	0.2-0.4 L/kg; relatively low Vd indicating limited extravascular distribution.
Bioavailability	Oral: 25-50% (variable, due to first-pass metabolism).
Onset of Action	Oral: 3-6 hours; Intravenous: 1-2 hours.
Duration of Action	10-16 hours; clinical effect may persist beyond plasma half-life due to active metabolites (e.g., methylnorepinephrine).

Classification & Brands

Dosing & administration

250 mg orally twice daily, increasing as needed up to 2 g/day in divided doses. Alternatively, 250-500 mg IV every 6 hours.

Dosage form	INJECTABLE
Renal impairment	Creatinine clearance 10-50 mL/min: dose every 8-12 hours. Clearance <10 mL/min: dose every 12-24 hours. Drug is removed by hemodialysis; administer a supplemental dose of 250-500 mg post-dialysis.
Liver impairment	Child-Pugh Class A: no adjustment. Class B: reduce initial dose by 50% (e.g., 250 mg/day). Class C: contraindicated due to reduced drug metabolism and risk of hepatic coma.
Pediatric use	10 mg/kg/day in 2-4 divided doses, up to 65 mg/kg/day or 3 g/day maximum. IV: 5-10 mg/kg every 6 hours.
Geriatric use	Initiate at 250 mg daily in divided doses; increase slowly. Elderly patients are more susceptible to sedation and hypotension; monitor closely for orthostatic effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Lithium may cause increased lithium toxicity Can cause hemolytic anemia and positive Coombs test.

FDA category	Human
Breastfeeding	Small amounts excreted into breast milk; M/P ratio approximately 0.2. Considered compatible with breastfeeding; monitor infant for hypotension or sedation.
Teratogenic Risk	First trimester: Limited human data; animal studies show no consistent teratogenicity. Second/third trimesters: No evidence of fetal harm; methyldopa is a first-line antihypertensive in pregnancy; chronic use may be associated with mild fetal growth restriction, reversible neonatal hypotension, and bradycardia.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Sedation
Serious Effects

Absolute Contraindications

["Hypersensitivity to methyldopa or any component","Active hepatic disease, such as acute hepatitis or active cirrhosis","Therapy with monoamine oxidase (MAO) inhibitors","Pheochromocytoma","Chronic use in patients with known hemolytic anemia (due to methyldopa therapy)"]

Clinical Precautions

Precautions

["Sedation and decreased mental acuity; avoid tasks requiring alertness","Positive Coombs test and hemolytic anemia (rare but discontinue if hemolysis occurs)","Hepatotoxicity (including hepatic necrosis); monitor liver function","May impair ability to drive or operate machinery","Orthostatic hypotension and syncope","Sodium and water retention; may require concomitant diuretic therapy","May interfere with laboratory tests (e.g., rise in serum creatinine, false increase in urinary catecholamines)","Abrupt withdrawal may cause rebound hypertension"]

Clinical Tips & Counseling

Drug interactions

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METHYLDOPATE HYDROCHLORIDE

Clinical safety rating: safe

Lithium may cause increased lithium toxicity Can cause hemolytic anemia and positive Coombs test.

How it works

What the body does with it

Metabolism	Hydrolyzed by esterases to methyldopa; methyldopa is metabolized primarily via sulfate conjugation (sulfotransferases) and to a lesser extent via O-methylation (catechol-O-methyltransferase) and renal excretion.
Excretion	Primarily renal excretion as sulfate conjugate (50-70%) and unchanged drug (20-30%); minimal biliary/fecal elimination (<5%).
Half-life	Terminal elimination half-life is 1.5-2 hours in normal renal function; clinically, due to prolonged pharmacodynamic effect, dosing is every 6-12 hours.
Protein binding	<15% bound to albumin.
Volume of Distribution	0.2-0.4 L/kg; relatively low Vd indicating limited extravascular distribution.
Bioavailability	Oral: 25-50% (variable, due to first-pass metabolism).
Onset of Action	Oral: 3-6 hours; Intravenous: 1-2 hours.
Duration of Action	10-16 hours; clinical effect may persist beyond plasma half-life due to active metabolites (e.g., methylnorepinephrine).

Classification & Brands

Dosing & administration

250 mg orally twice daily, increasing as needed up to 2 g/day in divided doses. Alternatively, 250-500 mg IV every 6 hours.

Dosage form	INJECTABLE
Renal impairment	Creatinine clearance 10-50 mL/min: dose every 8-12 hours. Clearance <10 mL/min: dose every 12-24 hours. Drug is removed by hemodialysis; administer a supplemental dose of 250-500 mg post-dialysis.
Liver impairment	Child-Pugh Class A: no adjustment. Class B: reduce initial dose by 50% (e.g., 250 mg/day). Class C: contraindicated due to reduced drug metabolism and risk of hepatic coma.
Pediatric use	10 mg/kg/day in 2-4 divided doses, up to 65 mg/kg/day or 3 g/day maximum. IV: 5-10 mg/kg every 6 hours.
Geriatric use	Initiate at 250 mg daily in divided doses; increase slowly. Elderly patients are more susceptible to sedation and hypotension; monitor closely for orthostatic effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Lithium may cause increased lithium toxicity Can cause hemolytic anemia and positive Coombs test.

FDA category	Human
Breastfeeding	Small amounts excreted into breast milk; M/P ratio approximately 0.2. Considered compatible with breastfeeding; monitor infant for hypotension or sedation.
Teratogenic Risk	First trimester: Limited human data; animal studies show no consistent teratogenicity. Second/third trimesters: No evidence of fetal harm; methyldopa is a first-line antihypertensive in pregnancy; chronic use may be associated with mild fetal growth restriction, reversible neonatal hypotension, and bradycardia.

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Common Effects	Sedation
Serious Effects