Schedule H

Oral

• Tablets: 1 mg, 2 mg, 4 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertension (Monotherapy or combination therapy)

Parameter Recommendation

Starting dose 1 mg once daily

Titration Increase at 2–4 week intervals based on blood pressure response

Usual maintenance dose 2–4 mg once daily

Maximum dose 8 mg once daily

Clinical notes In elderly or volume-depleted patients: initiate at 0.5 mg once daily; may combine with diuretics or CCBs if monotherapy inadequate

1. Heart failure post-myocardial infarction (with reduced ejection fraction) — Specialist initiated

Parameter Recommendation

Starting dose 0.5–1 mg once daily

Titration Double dose every 1–2 weeks as tolerated

Usual maintenance dose 2–4 mg once daily

Maximum dose 4 mg once daily

Clinical notes Initiate only after haemodynamic stability is established post-MI; monitor for symptomatic hypotension during up-titration

Secondary Indications – Adults (Off-label)

1. Diabetic nephropathy (Renoprotection) — OFF-LABEL

• Dose:

• Starting dose: 1 mg once daily

• Titration: Increase to 2–4 mg once daily based on tolerance and renal function

• Usual maintenance dose: 2–4 mg once daily

• Maximum dose: 4 mg once daily

• Duration: Chronic/long-term use

• Specialist only: Nephrologist supervision recommended

• Evidence basis: ACE inhibitor class effect evidence from major RCTs; not trandolapril-specific but used in Indian nephrology practice based on class efficacy for reducing proteinuria and slowing CKD progression

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable.

Secondary Indications – Paediatrics (Off-label)

Not applicable.

⚠️ Age Restriction Statement:

NOT RECOMMENDED below 18 years of age. Safety and efficacy data not established in paediatric population in Indian or international guidelines. No paediatric formulations available in India.

60 No dose adjustment required

30–60 Starting dose: 0.5 mg once daily; titrate cautiously with close monitoring

<30 Starting dose: 0.5 mg on alternate days; monitor serum potassium and creatinine closely

ESRD/Haemodialysis Use with extreme caution; avoid if haemodynamically unstable; specialist supervision only; trandolapril is not significantly dialysable

• History of angioedema with any ACE inhibitor (including hereditary/idiopathic angioedema)

• Known hypersensitivity to trandolapril or other ACE inhibitors

• Bilateral renal artery stenosis or stenosis in a solitary kidney

• Pregnancy (all trimesters)

• Haemodynamically significant aortic or mitral valve stenosis

• Hypertrophic obstructive cardiomyopathy

• Concurrent use of aliskiren in patients with diabetes mellitus or eGFR <60 mL/min/1.73m²

• Concurrent use of sacubitril/valsartan (minimum 36-hour washout required)

• Pre-existing renal impairment — risk of acute deterioration; monitor closely after initiation

• Volume depletion or concurrent high-dose diuretic therapy — risk of first-dose hypotension; consider temporary diuretic withdrawal or dose reduction before starting

• Hyperkalaemia risk — exercise caution with potassium supplements, potassium-sparing diuretics, or in diabetic patients

• Elderly patients — increased sensitivity to hypotensive effects

• Patients on lithium therapy — increased risk of lithium toxicity

• Collagen vascular disease (e.g., SLE, scleroderma) — increased risk of neutropenia

• Major surgery or anaesthesia — risk of hypotension

• Patients with aortic stenosis — may cause hypotension with reduced coronary perfusion

Parameter Information

Risk category Contraindicated — fetotoxic in all trimesters

Known fetal risks Oligohydramnios, fetal renal failure, neonatal hypotension, skull hypoplasia, limb contractures, pulmonary hypoplasia

Preferred alternatives Labetalol, methyldopa, or nifedipine (as per Indian obstetric guidelines)

When may be used Never — discontinue immediately if pregnancy is confirmed

What to monitor Ensure effective contraception in women of childbearing potential before initiating therapy

Parameter Information

Compatible with breastfeeding Not recommended — insufficient safety data

Preferred alternatives Enalapril (low milk transfer, better studied) or captopril; use under specialist supervision

Expected drug levels in milk Unknown; likely low based on pharmacokinetic profile

What to monitor in infant Feeding difficulties, lethargy, hypotension, poor weight gain

Parameter Recommendation

Starting dose 0.5 mg once daily

Titration Slower titration advisable; increase at 2–4 week intervals

Extra risks First-dose hypotension, postural hypotension with falls risk, acute kidney injury, electrolyte disturbances (hyperkalaemia, hyponatraemia)

Monitoring Close monitoring of blood pressure, renal function, and serum potassium essential

Interacting Drug Mechanism/Effect Recommendation

Potassium-sparing diuretics (spironolactone, eplerenone, amiloride) Additive hyperkalaemic effect Avoid combination or monitor potassium very closely; reduce doses if unavoidable

Potassium supplements Additive hyperkalaemia Avoid concurrent use unless documented hypokalaemia

Lithium ACE inhibitors reduce lithium excretion, increasing toxicity risk Avoid combination if possible; if essential, monitor lithium levels frequently

Aliskiren Dual RAAS blockade increases hypotension, hyperkalaemia, and renal impairment risk Contraindicated in diabetics or eGFR <60; avoid in other patients

ARBs (valsartan, losartan, etc.) Dual RAAS blockade Avoid combination — increased risk of hyperkalaemia, renal dysfunction, and hypotension

Sacubitril/valsartan Increased angioedema risk Do not co-administer; minimum 36-hour washout period required before switching

NSAIDs (including COX-2 inhibitors) Blunt antihypertensive effect; increased nephrotoxicity risk Avoid chronic concomitant use; monitor renal function if short-term use unavoidable

Interacting Drug Effect Recommendation

Loop diuretics (furosemide) / Thiazides Increased risk of first-dose hypotension Consider reducing or withholding diuretic 2–3 days before starting ACE inhibitor; start with lower dose

Antidiabetic agents (insulin, sulfonylureas, metformin) ACE inhibitors may enhance insulin sensitivity, increasing hypoglycaemia risk Monitor blood glucose more closely; may need to reduce antidiabetic doses

Gold compounds (sodium aurothiomalate) Nitritoid reactions (flushing, nausea, hypotension) Use with caution; monitor during gold injections

Immunosuppressants (ciclosporin, tacrolimus) Additive hyperkalaemic effect Monitor serum potassium closely

Antihypertensives (other classes) Additive hypotensive effect May be therapeutically beneficial but monitor for excessive BP reduction

Antituberculosis drugs (rifampicin) Potential reduced ACE inhibitor efficacy via hepatic enzyme induction Monitor blood pressure response

• Dry, persistent cough (most common; may occur weeks after initiation)

• Dizziness

• Headache

• Fatigue

• Hypotension (especially first-dose or with volume depletion)

• Transient elevation in serum creatinine (typically <30% rise; stabilises)

• Hyperkalaemia

• Nausea

Adverse Effect Clinical Features Action

Angioedema Swelling of face, lips, tongue, larynx; potentially life-threatening airway obstruction Discontinue permanently; emergency airway management; never rechallenge with any ACE inhibitor

Severe hypotension Syncope, shock (especially first dose in volume-depleted patients) Supportive care; IV fluids; reassess dose

Acute renal failure Rapid rise in creatinine, oliguria (especially with bilateral RAS) Discontinue; renal assessment; specialist input

Hyperkalaemia Potassium >6.0 mmol/L with cardiac arrhythmia risk Discontinue; treat hyperkalaemia urgently

Anaphylaxis Rare; with urticaria, bronchospasm, cardiovascular collapse Discontinue permanently; emergency management

Neutropenia/agranulocytosis Rare; higher risk with collagen vascular disease Monitor FBC in high-risk patients; discontinue if confirmed

Phase Parameters

Baseline Blood pressure, serum creatinine, eGFR, serum electrolytes (especially potassium), pregnancy test in women of childbearing potential

After initiation/dose change Blood pressure, serum creatinine, and potassium within 1–2 weeks

Long-term Renal function and electrolytes every 3–6 months; more frequently if renal impairment or concomitant potassium-affecting drugs

Heart failure patients Weight monitoring, signs of fluid overload, echocardiography for EF assessment as indicated

Single-ingredient formulations:

• Acetrand (Micro Labs)

• Apreace (Zydus)

• Tranepril (Sun Pharma)

• Trandolapril (generic)

Fixed-dose combinations:

• Note: FDCs with statins (e.g., Tonact-T) — verify composition before prescribing

Not currently under NPPA price control. Not included in NLEM 2022. Prices vary by brand and region.

1. Dry cough management: ACE inhibitor-induced cough may develop weeks to months after initiation; if intolerable, switch to an ARB rather than discontinuing RAAS blockade entirely

1. First-dose hypotension: Higher risk in patients on diuretics or with volume depletion; consider withholding diuretic for 2–3 days or starting with 0.5 mg dose

1. Once-daily advantage: Trandolapril has longer half-life than enalapril or captopril, making it suitable for once-daily dosing and improved adherence

1. Renal function monitoring: Expect mild rise in creatinine (up to 30%) after initiation — this is usually acceptable and stabilises; discontinue only if rise exceeds 30% or potassium rises significantly

1. Pregnancy absolute contraindication: Stop immediately if pregnancy detected; counsel all women of childbearing potential about contraceptive necessity

1. Post-MI benefit: Evidence from TRACE trial supports trandolapril use in post-MI patients with LV dysfunction; initiate once haemodynamically stable

Trandolapril; ACE inhibitor; hypertension; heart failure; post-MI; renal-dose-adjustment; pregnancy-contraindicated; hyperkalaemia-risk; once-daily; elderly-caution

RxIndia v1.0 — 22 Apr 2025

• CDSCO Product Information Database

• Indian Pharmacopoeia 2022

• API Textbook of Medicine, 11th Edition

• Harrison's Principles of Internal Medicine, 21st Edition

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• AIIMS Drug Formulary

• TRACE Trial (trandolapril post-MI evidence)

• ACE inhibitor class-effect RCTs/meta-analyses for nephropathy (off-label evidence)

• Indian cardiology and nephrology specialist practice consensus