Schedule H

Oral

• Tablet: 12.5 mg

• Tablet: 25 mg

• Fixed-dose combinations with ACE inhibitors, ARBs, and calcium channel blockers (various strengths)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertension (Monotherapy or Combination Therapy)

Parameter Recommendation

Starting dose 12.5 mg orally once daily

Titration May increase to 25 mg once daily after 2–4 weeks if BP response inadequate

Usual maintenance dose 12.5–25 mg once daily

Maximum dose 50 mg/day (rarely required; limited additional benefit beyond 25 mg with increased metabolic adverse effects)

Key Clinical Notes:

• First-line antihypertensive option, particularly in elderly and isolated systolic hypertension

• Often used in fixed-dose combinations with ACE inhibitors, ARBs, or CCBs

• Optimal antihypertensive effect achieved at 12.5–25 mg; higher doses offer minimal additional BP reduction

• Morning administration preferred to avoid nocturia

1. Oedema (Heart Failure, Hepatic Cirrhosis, Renal Disorders)

Parameter Recommendation

Starting dose 25–50 mg orally once daily

Titration Increase by 25 mg every 1–2 weeks if oedema persists

Usual maintenance dose 25–100 mg/day as single or divided doses

Maximum dose 100 mg/day

Key Clinical Notes:

• Less potent than loop diuretics for significant fluid overload

• Consider switching to loop diuretics (furosemide) if response suboptimal at maximum dose

• Not effective in advanced CKD (eGFR <30 mL/min/1.73 m²)

Secondary Indications — Adults Only (Off-label)

Indication Nephrolithiasis due to Idiopathic Hypercalciuria

Dose 25 mg orally once or twice daily

Duration Long-term; as per specialist guidance

Status OFF-LABEL; Specialist only (Nephrologist/Urologist)

Evidence Reduces urinary calcium excretion; supported by RCTs and international nephrology practice; used in Indian tertiary centres

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Oedema (Heart Failure, Nephrotic Syndrome)

6 months to 2 years 1–2 mg/kg/day in 1–2 divided doses 37.5 mg/day

2–12 years 1–2 mg/kg/day in 1–2 divided doses 37.5 mg/day

12 years 12.5–25 mg once daily; titrate as adult 50 mg/day

Key Clinical Notes:

• Monitor electrolytes, weight, and volume status closely

• Ensure adequate potassium intake or supplementation

Secondary Indications — Paediatric Doses (Off-label)

Indication Paediatric Hypertension

Dose 0.5–1 mg/kg/day orally in 1–2 divided doses

Maximum dose 25 mg/day

Status OFF-LABEL; Specialist only (Paediatric Nephrologist/Cardiologist)

Evidence Based on international paediatric hypertension guidelines; used in Indian tertiary paediatric centres

Safety Monitoring:

• Serum electrolytes (K⁺, Na⁺, Mg²⁺)

• Renal function

• Blood pressure response

• Growth parameters

⚠️ Not recommended below 6 months of age except under specialist supervision

30 No dose adjustment required

≤30 Avoid use — thiazides lose diuretic efficacy; switch to loop diuretic

Dialysis Ineffective; not recommended

Note: Thiazides work primarily by inhibiting sodium reabsorption in the distal convoluted tubule; this mechanism requires adequate tubular delivery, which is compromised in advanced CKD.

• Known hypersensitivity to hydrochlorothiazide or sulfonamide-derived drugs

• Anuria

• Severe renal impairment (eGFR <30 mL/min/1.73 m²)

• Hepatic coma or pre-coma

• Refractory hypokalaemia

• Refractory hyponatraemia

• Symptomatic hyperuricaemia (active gout)

• Addison's disease (untreated)

• Diabetes mellitus — may impair glycaemic control; monitor blood glucose

• Gout or hyperuricaemia — may precipitate acute gout attacks

• History of electrolyte imbalance — higher risk of hypokalaemia, hyponatraemia, hypomagnesaemia

• Elderly patients — increased susceptibility to volume depletion and orthostatic hypotension

• Dyslipidaemia — may cause mild increases in LDL cholesterol and triglycerides

• Concurrent lithium therapy — risk of lithium toxicity

• Systemic lupus erythematosus — may exacerbate or activate

• Hypercalcaemia — thiazides reduce urinary calcium excretion

Parameter Information

Risk category Not routinely recommended; may reduce placental perfusion

Preferred alternatives Methyldopa, labetalol, nifedipine for hypertension; furosemide if diuretic essential

When to use Only if clearly required for maternal benefit (e.g., severe heart failure); specialist supervision mandatory

Monitoring Fetal growth, amniotic fluid volume, maternal electrolytes, volume status

Parameter Information

Compatibility Compatible with breastfeeding; excreted in small amounts in breast milk

Preferred alternatives Labetalol, nifedipine for long-term hypertension management

Expected levels in milk Low

Infant monitoring Dehydration, poor feeding, inadequate weight gain

Parameter Recommendation

Starting dose 12.5 mg once daily

Titration Slow titration; reassess after 2–4 weeks before increasing dose

Extra risks Orthostatic hypotension, falls, electrolyte disturbances (especially hyponatraemia), volume depletion, acute kidney injury

Monitoring Electrolytes and renal function within 1–2 weeks of initiation; BP (lying and standing)

Note: Lower doses (12.5 mg) are often effective in elderly patients and better tolerated.

Interacting Drug/Class Mechanism Clinical Effect Recommendation

Lithium Reduced renal lithium clearance Lithium toxicity Avoid combination; if essential, monitor lithium levels closely

Digoxin Thiazide-induced hypokalaemia Digoxin toxicity (arrhythmias) Monitor potassium; supplement or add potassium-sparing agent

NSAIDs (chronic use) Inhibit prostaglandin-mediated renal blood flow Reduced antihypertensive and diuretic efficacy; increased AKI risk Avoid long-term co-administration

Dofetilide Hypokalaemia potentiates QT prolongation Torsades de pointes Contraindicated

QT-prolonging drugs (Class III antiarrhythmics) Additive QT prolongation via hypokalaemia Ventricular arrhythmias Monitor electrolytes; correct hypokalaemia

Interacting Drug/Class Effect Recommendation

ACE inhibitors / ARBs Additive hypotension; first-dose hypotension risk Start ACE/ARB at low dose; monitor BP

Loop diuretics Additive volume depletion and electrolyte imbalance Monitor closely; may be intentional sequential nephron blockade

Antidiabetic agents (insulin, sulfonylureas) Reduced glycaemic control Monitor blood glucose; adjust antidiabetic doses

Corticosteroids Enhanced hypokalaemia Monitor potassium; supplement if needed

Carbamazepine Additive hyponatraemia Monitor sodium levels

Antipsychotics (haloperidol, risperidone) Hypokalaemia increases QTc risk Monitor electrolytes and ECG

Cholestyramine, colestipol Reduced HCTZ absorption Administer HCTZ 1 hour before or 4–6 hours after resin

• Hypokalaemia

• Hyponatraemia

• Hypomagnesaemia

• Hyperuricaemia

• Hyperglycaemia

• Hypercalcaemia (mild)

• Dizziness

• Orthostatic hypotension

• Polyuria

• Muscle cramps

• Fatigue

Adverse Effect Action Required

Severe hyponatraemia (confusion, seizures) Discontinue; correct sodium cautiously; hospitalisation may be required

Severe hypokalaemia (arrhythmias, paralysis) Discontinue; IV potassium replacement; cardiac monitoring

Acute pancreatitis (rare) Discontinue immediately; supportive care

Stevens-Johnson Syndrome / TEN (rare) Discontinue immediately; hospitalisation; dermatology consultation

Agranulocytosis / aplastic anaemia (very rare) Discontinue; haematology consultation

Acute angle-closure glaucoma (rare) Discontinue; urgent ophthalmology referral

Phase Parameters

Baseline Serum electrolytes (Na⁺, K⁺, Mg²⁺), renal function (creatinine, eGFR), uric acid, fasting glucose, lipid profile, BP

After initiation/dose change Electrolytes and renal function at 1–2 weeks

Long-term Electrolytes, renal function, uric acid, fasting glucose every 3–6 months; BP and weight at each visit

Plain Formulations:

• Esidrex

• Hydrazide

• Aquazide

Common Fixed-Dose Combinations:

Note: Listed in NLEM India 2022; commonly used combinations under NPPA price control

1. Optimal dose for hypertension is 12.5–25 mg/day — Higher doses provide minimal additional BP reduction but significantly increase metabolic adverse effects (hypokalaemia, hyperglycaemia, hyperuricaemia)

1. Ineffective in advanced CKD — Thiazides lose diuretic efficacy when eGFR falls below 30 mL/min/1.73 m²; switch to loop diuretics in such patients

1. Check electrolytes early — Monitor potassium and sodium at 1–2 weeks after initiation or dose change; hypokalaemia and hyponatraemia are common

1. Combine with ACE inhibitor/ARB strategically — Helps counteract thiazide-induced hypokalaemia; also provides additive antihypertensive effect

1. Preferred in elderly for uncomplicated hypertension — Well-established cardiovascular outcome benefits (ALLHAT, SHEP trials); low cost and extensive safety data

1. Caution with sulfa allergy — Though cross-reactivity is rare, document allergy status; avoid if history of severe sulfonamide hypersensitivity reaction

Hydrochlorothiazide; HCTZ; thiazide diuretic; hypertension; oedema; electrolyte monitoring; hypokalaemia; elderly-preferred; NLEM India; pregnancy-caution; nephrolithiasis off-label

RxIndia v1.0 — 24 Apr 2025

• CDSCO-approved product insert

• Indian Pharmacopoeia

• NLEM India 2022

• API Textbook of Medicine

• AIIMS Delhi Adult Medicine Formulary

• ICMR Guidelines on Hypertension

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Indian Paediatric Nephrology Guidelines

• ALLHAT, SHEP trials (for clinical outcomes evidence)