Schedule H

Oral

• Tablets: 250 mg, 500 mg

Note: Parenteral formulation (injection) is NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertensive Disorders of Pregnancy (Gestational Hypertension, Chronic Hypertension in Pregnancy, Pre-Eclampsia — Maintenance Therapy)

Oral Route

Step Dose Clinical Notes

Starting dose 250 mg twice or three times daily Begin with lowest effective dose

Titration Increase by 250 mg/day every 2–3 days Based on BP response; divided into 2–3 doses

Usual maintenance dose 500 mg–2 g/day in 2–3 divided doses Most patients controlled at 750 mg–1 g/day

Maximum dose 3 g/day Rarely required; CNS side effects dose-limiting

Key points:

• Drug of choice for chronic/maintenance hypertension in pregnancy per Indian obstetric guidelines

• NOT for acute severe hypertension — use labetalol or hydralazine IV for emergencies

• Onset of action: 6–8 hours; full effect may take 24–48 hours

• Safe throughout all trimesters of pregnancy

1. Essential Hypertension (Non-Pregnant Adults)

Oral Route

Step Dose Clinical Notes

Starting dose 250 mg twice daily May start with 250 mg once daily if sensitive to hypotension

Titration Increase by 250–500 mg/day every 2–3 days In divided doses

Usual maintenance dose 500 mg–2 g/day in 2–4 divided doses Evening dosing may reduce daytime sedation

Maximum dose 3 g/day Higher doses limited by CNS adverse effects

Key points:

• Not first-line for essential hypertension in modern practice (CCBs, ACE inhibitors preferred)

• May be used when other agents contraindicated or in combination therapy

• Significant sedation may limit tolerability

Secondary Indications — Adults (Off-label)

Not applicable. No established off-label indications documented in Indian guidelines.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Hypertension in Children

Oral Route — Weight-Based

Step Dose Clinical Notes

Starting dose 10 mg/kg/day in 2–4 divided doses Start at lower end

Titration Increase every 2–3 days based on BP response In divided doses

Usual maintenance dose 20–40 mg/kg/day in 2–4 divided doses Individualise based on response

Maximum dose 65 mg/kg/day OR 3 g/day (whichever is lower)

Safety monitoring:

• Blood pressure at each visit

• LFTs at baseline and every 3–6 months

• CBC including reticulocyte count periodically

• Monitor for sedation, behavioural changes

Secondary Indications — Paediatrics (Off-label)

Not applicable.

Minimum age: Not recommended in neonates and infants below 1 year of age except under paediatric nephrology/cardiology specialist supervision

Note: Methyldopa metabolites accumulate in renal impairment — increased risk of sedation and hypotension

Note: Methyldopa can cause idiosyncratic hepatotoxicity; prior methyldopa-induced liver disease is absolute contraindication

• Active liver disease (acute hepatitis, cirrhosis with active decompensation)

• History of methyldopa-induced liver disorders (hepatitis, hepatic necrosis)

• History of methyldopa-induced haemolytic anaemia

• Concurrent use with monoamine oxidase inhibitors (MAOIs)

• Phaeochromocytoma (may cause paradoxical hypertensive crisis)

• Known hypersensitivity to methyldopa or any excipient

• Depression with suicidal ideation (may worsen)

• History of depression or psychiatric disorders — may exacerbate

• Renal impairment — dose adjustment required; increased sensitivity

• Dialysis patients — dose after dialysis session

• Elderly patients — increased sensitivity to sedation and orthostatic hypotension

• Concurrent anaesthesia — may potentiate hypotensive effects

• Parkinson's disease — may worsen symptoms

• Bilateral cerebrovascular disease — risk of hypoperfusion

• History of drug-induced haemolytic anaemia (other causes)

• Abrupt discontinuation — may cause rebound hypertension (taper over 2–3 days)

Parameter Recommendation

Safety category SAFE — extensively studied in pregnancy; longest safety record of any antihypertensive in pregnancy

Preferred alternatives Labetalol (alternative first-line; preferred for faster onset); nifedipine (alternative)

When it may be used First-line for chronic/gestational hypertension maintenance throughout all trimesters; NOT for acute severe hypertension (use IV labetalol or hydralazine)

Monitoring Maternal: BP, LFTs, CBC with reticulocyte count every 4–6 weeks with prolonged use; Fetal: Growth surveillance (IUGR not associated but monitor routinely)

Notes:

• Drug of choice in Indian obstetric practice for maintenance BP control

• May cause transient neonatal hypotension if used close to delivery — observe neonate

• Consider switching to labetalol postpartum if sedation problematic

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Low (milk:plasma ratio ~0.2–0.3; infant receives <0.1% of maternal weight-adjusted dose)

Preferred alternatives Labetalol, nifedipine, enalapril (if not breastfeeding premature neonate)

Infant monitoring Observe for sedation, poor feeding, hypotension; routine monitoring usually sufficient

• Recommended starting dose: 125 mg twice daily (half of usual starting dose)

• Titration: Slower titration intervals (every 5–7 days); smaller increments

• Additional risks:

• Increased sensitivity to CNS effects (sedation, confusion, depression)

• Higher risk of orthostatic hypotension — fall risk

• May cause or worsen cognitive impairment

• Increased susceptibility to bradycardia

• Reduced renal function — may require dose adjustment

• Recommendation: Not preferred antihypertensive in elderly; consider CCBs, ACE inhibitors, or ARBs as first-line

Drug Interaction Management

MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) Risk of hypertensive crisis due to catecholamine release CONTRAINDICATED — do not use together; allow 2-week washout

Levodopa/Carbidopa Reduced efficacy of both drugs; risk of CNS adverse effects (confusion, psychosis) AVOID combination if possible; if essential, monitor closely

Iron salts (oral ferrous sulphate, ferrous fumarate) Iron chelates methyldopa in GI tract → reduced methyldopa absorption by 50–70% Separate administration by at least 2 hours

Lithium Increased lithium levels and toxicity risk Monitor lithium levels closely; may need lithium dose reduction

Sympathomimetics (phenylephrine, pseudoephedrine) Reduced antihypertensive effect; possible paradoxical hypertension Avoid combination if possible

Drug Interaction Management

Other antihypertensives (beta-blockers, diuretics, CCBs, ACE inhibitors) Additive hypotensive effects Common combinations; monitor BP; adjust doses as needed

Tricyclic antidepressants (amitriptyline, imipramine) May reduce antihypertensive effect Monitor BP; may need methyldopa dose increase

NSAIDs (chronic use) May reduce antihypertensive efficacy via sodium and fluid retention Avoid prolonged NSAID use; monitor BP

General anaesthetics Enhanced hypotensive effect Inform anaesthetist; may need dose reduction of anaesthetic

Alcohol Additive CNS depression and hypotension Advise moderation

Haloperidol and other antipsychotics Additive CNS effects; may worsen extrapyramidal symptoms Monitor for excessive sedation

• Sedation and drowsiness (very common — may diminish with continued use)

• Dry mouth

• Headache

• Nasal congestion

• Orthostatic hypotension

• Fatigue and weakness

• Dizziness

• Oedema

• Weight gain

• Decreased libido / Sexual dysfunction

Reaction Action Required

Hepatotoxicity (drug-induced hepatitis, hepatic necrosis) Discontinue permanently; monitor LFTs; hepatology referral if severe; contraindicated for future use

Haemolytic anaemia (Coombs-positive) Discontinue permanently; may need corticosteroids or transfusion in severe cases; contraindicated for future use

Fever of unknown origin (drug fever) Discontinue; fever resolves within 24–72 hours; do not rechallenge

Lupus-like syndrome (fever, arthralgia, positive ANA) Discontinue; usually reversible

Severe depression or psychosis Discontinue; psychiatric evaluation

Bone marrow suppression (leucopenia, thrombocytopenia — rare) Discontinue; haematology referral

Myocarditis/Pericarditis (rare) Discontinue; cardiology evaluation

Pancreatitis (rare) Discontinue; supportive management

At 2–4 weeks BP response; LFTs; assess for sedation

First 3 months LFTs monthly initially if using higher doses; monitor for fever, jaundice, unexplained malaise

Long-term (>6 months) LFTs and CBC every 6 months; Direct Coombs test (positive in 10–20% but haemolysis rare); assess for depression

In pregnancy LFTs, CBC, reticulocyte count every 4–6 weeks

Clinical note: Positive Coombs test occurs in 10–20% of patients on prolonged therapy; haemolytic anaemia is rare (1–2%) but requires immediate discontinuation

Single-ingredient products:

• Aldomet (MSD — limited availability now)

• Alphadopa (Glaxo/VHB)

• Dopamet (Cipla)

• Methyldopa IP (generic — multiple manufacturers including IPCA, Alkem)

Note: Primarily available as oral tablets; parenteral formulation is NOT available in India

NLEM status: Methyldopa tablet 250 mg is included in NLEM 2022 — ceiling price applicable under NPPA

Government supply: Available through public health facilities, ESI hospitals, and NHM/NRHM maternal health programmes

• Pregnancy drug of choice: Methyldopa has the longest safety record in pregnancy; preferred for chronic/maintenance hypertension control — NOT for acute severe hypertension emergencies

• Slow onset: Takes 6–8 hours to start working; full effect in 24–48 hours — do not expect rapid BP reduction; use labetalol IV for hypertensive emergencies

• Sedation is dose-limiting: Start low, titrate slowly; evening-weighted dosing may improve daytime tolerability

• Iron interaction: Very common oversight — separate oral iron supplements by at least 2 hours or iron absorption severely reduced

• Monitor liver function: Hepatotoxicity can occur anytime but most common in first 2–3 months; discontinue immediately if unexplained fever, malaise, or LFT elevation

• Consider postpartum switch: Many patients prefer switching to labetalol or other agents postpartum due to sedation burden of methyldopa

methyldopa; antihypertensive; pregnancy-safe; gestational hypertension; pre-eclampsia; centrally acting; alpha-2 agonist; hepatotoxicity risk; Coombs positive; NLEM India

RxIndia v1.1 — 14 Jun 2025

• CDSCO Approved Product Information

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• NLEM 2022 (National List of Essential Medicines)

• MoHFW Guidelines on Hypertensive Disorders in Pregnancy

• FOGSI Good Clinical Practice Recommendations

• AIIMS Obstetrics Protocols

• API Textbook of Medicine (11th Edition)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th Edition)

• Harrison's Principles of Internal Medicine (21st Edition)