Methyldopa

Approved Indications

• Hypertension (Essential and Secondary)
• First-line or adjunct therapy in mild to moderate hypertension
• Often used in pregnancy-induced hypertension (PIH) or chronic hypertension during pregnancy

Clinically Accepted Off-label Uses

• Hypertensive emergencies in pregnancy (including preeclampsia)
• Postpartum hypertension (especially in breastfeeding patients)
• Hypertension in patients with chronic kidney disease (CKD) when ACE inhibitors or ARBs are contraindicated or poorly tolerated

Route of Administration: Oral

Adults (Non-pregnant)

• Initial dose: 250 mg two to three times daily
• Titration: Increase every 2 days based on response
• Usual maintenance dose: 500 mg to 2,000 mg/day in 2–4 divided doses
• Maximum dose: 3,000 mg/day

Pregnant Women

• Initial dose: 250 mg two to three times daily
• Maintenance dose: Typically 500–2,000 mg/day, adjusted based on blood pressure and fetal safety
• Preferred due to long-term safety in pregnancy

Elderly

• Start at lower initial dose (e.g., 125 mg twice daily)
• Titrate cautiously due to risk of orthostatic hypotension and sedation

Pediatrics

• Initial dose: 10 mg/kg/day in 2–4 divided doses
• Maximum dose: 65 mg/kg/day or 3,000 mg/day, whichever is lower
• Use under pediatric supervision only

Renal Impairment

• Methyldopa is primarily renally excreted
• Dose reduction recommended in patients with moderate to severe renal impairment
• Monitor renal function and adjust dosing accordingly

Methyldopa is a centrally acting alpha-2 adrenergic agonist. After oral administration, methyldopa is transported across the blood-brain barrier and converted to alpha-methyl norepinephrine, a false neurotransmitter that replaces norepinephrine in sympathetic nerve terminals. This metabolite stimulates central alpha-2 adrenergic receptors, leading to inhibition of sympathetic outflow from the central nervous system (CNS). As a result, peripheral vascular resistance decreases, reducing blood pressure without significantly affecting heart rate or cardiac output.

• Absorption: Well absorbed orally (~50% bioavailability)
• Distribution: Widely distributed; crosses the placenta and enters breast milk
• Metabolism: Partially metabolized in the liver; active metabolite is alpha-methyl norepinephrine
• Elimination: Primarily renal (urine)
• Half-life:
• Methyldopa: ~1.5 to 2 hours
• Antihypertensive effect: May last 12–24 hours
• Onset of Action: Within 4 to 6 hours
• Peak Effect: 6 to 8 hours
• Duration: Up to 24 hours depending on dose

Pregnancy

• FDA Category B
• Considered one of the safest antihypertensive medications during all trimesters of pregnancy
• Widely used for managing chronic hypertension and preeclampsia
• No known teratogenic effects based on extensive clinical data

Lactation

• Excreted in low concentrations in breast milk
• Generally considered safe for use during breastfeeding
• Monitor infants for drowsiness or hypotension, although adverse effects are rare

• Primary Class: Antihypertensive
• Subclass: Centrally Acting Alpha-2 Adrenergic Agonist
• Pharmacologic Category: Sympatholytic agent

• Known hypersensitivity to methyldopa or its components
• Active hepatic disease (including acute hepatitis and active cirrhosis)
• History of methyldopa-induced liver disorders
• Monoamine oxidase inhibitor (MAOI) use
• Severe depression or history of depressive illness (relative contraindication)
• Pheochromocytoma (can interfere with catecholamine testing)

• Hepatic toxicity: Monitor liver function tests; discontinue if jaundice or abnormal LFTs develop
• Hemolytic anemia: Associated with positive Coombs test; monitor CBC regularly
• CNS depression: May cause drowsiness, sedation, or mental clouding; caution when operating machinery
• Orthostatic hypotension: Especially in elderly or volume-depleted patients
• Withdrawal syndrome: Sudden discontinuation may cause rebound hypertension
• Depression: Monitor mood changes, especially in those with a prior history
• Rare fever or lupus-like syndrome: Discontinue if signs appear

Common

• Central Nervous System:
• Drowsiness, sedation
• Dizziness, headache
• Cardiovascular:
• Orthostatic hypotension
• Bradycardia
• Gastrointestinal:
• Dry mouth
• Nausea, vomiting, diarrhea
• Genitourinary:
• Sexual dysfunction, decreased libido

Less Common / Serious

• Hepatotoxicity (elevated liver enzymes, hepatitis)
• Hemolytic anemia, positive Coombs test
• Depression, confusion, psychosis
• Edema, weight gain
• Drug fever, lupus-like syndrome
• Rare: myocarditis or pericarditis

Onset: Most CNS effects occur within days; hematologic and hepatic effects may appear after weeks to months
Dose-dependence: Some side effects (e.g., sedation, dry mouth) are dose-dependent

• MAO inhibitors: Contraindicated; risk of hypertensive crisis
• Other antihypertensives: Additive hypotensive effects
• Lithium: May increase lithium toxicity
• Levodopa: Antagonistic interaction (competes for decarboxylase enzyme)
• Iron supplements: May reduce methyldopa absorption; separate administration by at least 2 hours
• Alcohol: May exacerbate CNS depression and hypotension
• Enzyme Systems: Primarily metabolized via liver enzymes; minimal CYP450 involvement

• ACOG (American College of Obstetricians and Gynecologists): Continues to list methyldopa as a first-line agent for hypertension in pregnancy (2023 update)
• WHO Guidelines (2023): Reaffirmed as a safe option for managing chronic hypertension during pregnancy
• No major dosing or safety changes from FDA or EMA in the past 2 years

• Temperature: Store below 25°C
• Humidity: Keep in a dry environment
• Light Protection: Store in original container, protected from light
• Handling Precautions:
• Protect from moisture
• Do not use tablets that are chipped or discolored
• Reconstitution: Not applicable (oral tablet)