Schedule H

Oral, Intravenous

• Tablets (Immediate Release): 30 mg, 60 mg, 90 mg

• Extended-Release Tablets/Capsules: 90 mg, 120 mg, 180 mg, 240 mg, 300 mg

• Injection: 5 mg/mL (5 mL ampoule)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Hypertension

A. Immediate-Release Formulation (Adults)

Step Dose Clinical Notes

Starting dose 30–60 mg twice daily Take with or without food

Titration Increase every 7–14 days based on BP response Assess tolerability before each increment

Usual maintenance dose 180–360 mg/day in 2–3 divided doses Adjust based on individual BP targets

Maximum dose 360 mg/day (IR formulation) Higher doses rarely provide additional benefit

B. Extended-Release Formulation (Adults)

Step Dose Clinical Notes

Starting dose 120–180 mg once daily Swallow whole; do not crush or chew

Titration Increase every 7–14 days as needed Monitor for bradycardia

Usual maintenance dose 180–360 mg once daily Preferred for better compliance

Maximum dose 540 mg/day Under specialist supervision

Key points:

• Extended-release formulations preferred for steady BP control and improved adherence

• Monitor heart rate; avoid in patients with resting HR <50 bpm

1. Chronic Stable Angina / Vasospastic (Prinzmetal's) Angina

Immediate-Release Formulation (Adults)

Step Dose Clinical Notes

Starting dose 30 mg four times daily OR 60 mg three times daily Space doses evenly throughout day

Titration Increase every 3–7 days based on symptom control Monitor HR and conduction

Usual maintenance dose 180–360 mg/day in divided doses Titrate to angina relief

Maximum dose 480 mg/day Higher doses require close monitoring

Extended-Release Formulation (Adults)

Step Dose Clinical Notes

Starting dose 120–180 mg once daily Morning dosing preferred

Titration Increase weekly as tolerated Assess exercise tolerance

Usual maintenance dose 180–360 mg once daily Based on symptom response

Maximum dose 480 mg/day

Key points:

• Particularly effective for vasospastic angina

• May be combined with nitrates; avoid combination with beta-blockers unless closely monitored

1. Atrial Fibrillation / Atrial Flutter — Acute Rate Control (IV Route)

Step Dose Clinical Notes

Initial bolus 0.25 mg/kg IV over 2 minutes Typical adult dose: 15–20 mg

Second bolus (if inadequate response) 0.35 mg/kg IV after 15 minutes Typical adult dose: 20–25 mg

Maintenance infusion 5–15 mg/hour IV Titrate to target HR 80–110 bpm

Transition Convert to oral therapy once stable Use equivalent total daily dose

Key points:

• Use only in monitored setting (CCU/ICU/emergency)

• Ensure no pre-excitation (WPW syndrome) before use — contraindicated in AF with WPW

• Have IV calcium gluconate and pacing capability available

• Avoid in patients with LVEF <40%

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Supraventricular Tachycardia (SVT) — Acute Termination IV bolus 0.25 mg/kg over 2 min; may repeat at 0.35 mg/kg after 15 min Single episode termination OFF-LABEL; Specialist cardiology input required; Evidence: RCTs support efficacy; alternative when adenosine contraindicated/failed

Hypertrophic Cardiomyopathy (symptomatic) Oral 180–360 mg/day in divided doses Long-term OFF-LABEL; Specialist only; Evidence: Indian cardiology practice for patients intolerant to beta-blockers

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Supraventricular Tachycardia — Acute Management (IV Route)

Age Initial Bolus Repeat Bolus Maintenance Infusion

1–17 years 0.25 mg/kg IV over 2 minutes (max 20 mg) 0.35 mg/kg after 15 min if needed (max 25 mg) 0.1–0.25 mg/kg/hour

Key points:

• Requires continuous ECG monitoring

• Have resuscitation equipment and atropine available

• Avoid in infants <1 year due to risk of profound bradycardia, hypotension, and cardiac arrest

Secondary Indications — Paediatrics (Off-label)

Indication Dose Duration Notes

Hypertension (chronic) 1–2 mg/kg/day orally in 3 divided doses (max 3.5 mg/kg/day up to 360 mg/day) Long-term OFF-LABEL; Age ≥6 years only; Specialist paediatric cardiology/nephrology supervision; Evidence: International paediatric cardiology consensus

Safety monitoring:

• Heart rate and blood pressure at each visit

• ECG before initiation and periodically during treatment

• Liver function tests every 6–12 months with chronic use

Minimum age: Not recommended below 1 year of age. Use between 1–6 years only under specialist supervision with compelling indication.

Notes:

• Diltiazem is primarily hepatically metabolised

• Use with caution in severe renal dysfunction due to potential haemodynamic effects and fluid retention

• Not significantly removed by haemodialysis

Note: Diltiazem undergoes extensive first-pass hepatic metabolism; bioavailability increases significantly in hepatic impairment

• Sick sinus syndrome (without functioning pacemaker)

• Second-degree or third-degree AV block (without functioning pacemaker)

• Severe bradycardia (HR <40 bpm)

• Hypotension (SBP <90 mmHg) or cardiogenic shock

• Acute decompensated heart failure or heart failure with reduced ejection fraction (LVEF <40%)

• Atrial fibrillation/flutter with accessory pathway (e.g., WPW syndrome) — risk of ventricular fibrillation

• Known hypersensitivity to diltiazem or any excipient

• Concurrent use with IV beta-blockers (within few hours)

• Concurrent use with ivabradine

• Mild-to-moderate LV systolic dysfunction (LVEF 40–50%) — use with close monitoring

• First-degree AV block or baseline conduction abnormalities

• Bradycardia (HR 50–60 bpm) — may worsen with diltiazem

• Concurrent oral beta-blocker therapy — increased risk of AV block and bradycardia; requires careful dose titration

• Concurrent digoxin use — additive AV nodal suppression

• Elderly patients — increased sensitivity to negative chronotropic and hypotensive effects

• Hepatic impairment — reduced clearance

• Concurrent strong CYP3A4 inhibitors or substrates

• Patients on high-dose statins — myopathy risk

Parameter Recommendation

Safety category Limited human data; animal studies show embryotoxicity at high doses; avoid unless essential

Preferred alternatives Methyldopa (first-line for chronic hypertension); labetalol (for acute hypertension); nifedipine (for tocolysis or hypertensive urgency)

When it may be used Only if other antihypertensives contraindicated/ineffective and benefit clearly outweighs risk; specialist obstetric and cardiology input required

Monitoring Maternal: BP, HR, ECG; Fetal: heart rate monitoring, growth surveillance via ultrasound

Parameter Recommendation

Compatibility Compatible with caution — diltiazem and metabolites present in breast milk

Drug levels in milk Low (milk:plasma ratio ~1:1; infant exposure estimated <1% of maternal dose)

Preferred alternatives Nifedipine or amlodipine if CCB required (more lactation data available)

Infant monitoring Observe for bradycardia, poor feeding, lethargy, hypotension; avoid ER formulations if possible

• Recommended starting dose: 30 mg twice daily (IR) or 120 mg once daily (ER)

• Titration: Slower titration intervals (every 2 weeks); cautious dose escalation

• Additional risks:

• Increased susceptibility to bradycardia and AV block

• Higher risk of hypotension and orthostatic symptoms — fall risk

• Constipation more common and may be severe

• Negative inotropic effects may precipitate heart failure in borderline cardiac function

• Polypharmacy concerns — review for drug interactions

• Monitoring: Regular HR, BP, ECG; assess for constipation and peripheral oedema

Drug Interaction Management

Beta-blockers (oral) Additive negative chronotropic and dromotropic effects → severe bradycardia, AV block, hypotension Avoid combination or use with extreme caution; start both at lowest doses; monitor ECG closely

Beta-blockers (IV) Profound bradycardia, hypotension, asystole CONTRAINDICATED — do not administer within several hours of each other

Ivabradine Additive bradycardia CONTRAINDICATED

Digoxin Increased digoxin levels (by 20–50%) + additive AV nodal suppression Monitor digoxin levels; reduce digoxin dose; ECG monitoring

Simvastatin / Lovastatin Diltiazem inhibits CYP3A4 → markedly increased statin levels → myopathy/rhabdomyolysis risk Limit simvastatin to ≤10 mg/day; avoid lovastatin >20 mg/day; consider atorvastatin or rosuvastatin

Cyclosporine / Tacrolimus Diltiazem inhibits CYP3A4 → increased immunosuppressant levels and nephrotoxicity Monitor drug levels closely; reduce immunosuppressant dose

Carbamazepine Increased carbamazepine levels → toxicity (ataxia, nystagmus, diplopia) Monitor carbamazepine levels; reduce dose if needed

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) Increased diltiazem levels → enhanced effects and toxicity Reduce diltiazem dose; monitor HR and BP closely

Drug Interaction Management

ACE inhibitors / ARBs Additive hypotensive effect Usually beneficial combination; monitor BP

Diuretics Additive hypotension Monitor BP; adjust doses as needed

Rifampicin Potent CYP3A4 inducer → markedly reduced diltiazem levels and efficacy Avoid combination if possible; if essential, increase diltiazem dose substantially with monitoring

Phenytoin Increased phenytoin levels (variable); phenytoin may reduce diltiazem levels Monitor phenytoin levels; clinical monitoring for efficacy

Theophylline Reduced theophylline clearance Monitor theophylline levels

Atorvastatin / Rosuvastatin Less interaction than simvastatin; modest increase in statin levels Preferred statins with diltiazem; still monitor for myopathy symptoms

DOACs (apixaban, rivaroxaban) Diltiazem may increase DOAC levels via P-gp and CYP3A4 inhibition Monitor for bleeding; consider dose reduction in high-risk patients

Lithium Possible neurotoxicity Monitor lithium levels and for neurotoxic symptoms

Buspirone Increased buspirone levels Monitor for sedation; reduce buspirone dose

• Peripheral oedema (dose-related)

• Headache

• Dizziness

• Flushing

• Bradycardia

• Fatigue / asthenia

• Constipation

• Nausea

• First-degree AV block

Reaction Action Required

High-degree AV block (second/third-degree) Discontinue immediately; may require temporary pacing; atropine for symptomatic bradycardia

Severe sinus bradycardia (<40 bpm) Discontinue; supportive care; atropine or pacing if symptomatic

Marked hypotension Discontinue or reduce dose; IV fluids; IV calcium gluconate for severe cases

Acute heart failure / Pulmonary oedema Discontinue immediately; standard HF management

Hepatotoxicity (elevated transaminases, cholestatic jaundice) Discontinue; monitor LFTs; hepatology referral if severe

Stevens-Johnson Syndrome / TEN (rare) Discontinue permanently; hospitalise

Severe skin reactions (exfoliative dermatitis) Discontinue; dermatology referral

After initiation/dose change HR and BP at 1 week; ECG if conduction concerns or symptoms of bradycardia

During IV infusion Continuous ECG and BP monitoring; HR every 15 minutes during titration

Long-term (every 3–6 months) BP; HR; clinical assessment for oedema, constipation, fatigue

Annually ECG (especially if on high dose or HR trending low); LFTs

Immediate-Release:

• Dilzem (Torrent)

• Angizem (Intas)

• Dilcontin (Cadila)

• DTM (Sun Pharma)

Extended-Release:

• Angizem CD (Intas)

• Dilzem CD (Torrent)

• Diltime OD (Cadila)

• Channel (Zydus)

Injection:

• Dilzem Injection (Torrent)

• Angizem Injection (Intas)

NLEM status: Diltiazem 30 mg tablet and 60 mg tablet are included in NLEM 2022 — ceiling price applicable under NPPA

• Rate control agent of choice: Preferred over verapamil for AF/flutter rate control due to less negative inotropy; use when beta-blockers contraindicated or not tolerated

• Not for HFrEF: Avoid in heart failure with reduced ejection fraction (LVEF <40%) — negative inotropy can worsen outcomes

• Beta-blocker combination caution: If combination necessary (e.g., refractory angina), start both at lowest doses and monitor ECG closely for AV block

• Statin interaction: Remember to limit simvastatin to 10 mg/day; switch to atorvastatin or rosuvastatin if higher statin dose needed

• ER vs IR: Extended-release formulations improve adherence and provide smoother BP/HR control — prefer for chronic use

• IV diltiazem: Use only in monitored setting; have calcium gluconate and pacing available; beware of WPW syndrome

hypertension; angina; atrial fibrillation; rate control; CCB; non-dihydropyridine; bradycardia risk; CYP3A4 inhibitor; statin interaction; NLEM India

RxIndia v1.1 — 14 Jun 2025

• CDSCO Approved Product Information

• Indian Pharmacopoeia 2022

• NLEM 2022 (National List of Essential Medicines)

• API Textbook of Medicine (11th Edition)

• ICMR Guidelines on Hypertension Management

• AIIMS Cardiology Protocols

• IAP Guidelines (Paediatric Arrhythmia Management)

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

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

• Cardiological Society of India — AF Management Guidelines