schedule H

Oral, Intravenous

• Tablets: 0.25 mg

• Oral solution (paediatric): 0.05 mg/mL

• Injection: 0.25 mg/mL (2 mL ampoule)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Congestive Heart Failure (HFrEF) — Symptomatic control, especially with concurrent atrial fibrillation

A. Oral Route

Parameter Recommendation

Starting dose 0.125–0.25 mg once daily

Titration Adjust based on clinical response, heart rate, and serum digoxin levels after 1 week

Usual maintenance dose 0.125–0.25 mg once daily

Maximum dose 0.25 mg/day (0.5 mg/day only in exceptional cases with close monitoring)

B. Intravenous Route (when oral not feasible or rapid control needed)

Parameter Recommendation

Starting dose (Loading) 0.25–0.5 mg IV over 15–30 minutes

Titration Additional 0.25 mg IV every 6 hours × 2 doses (total loading: 0.75–1 mg over 24 hours)

Usual maintenance dose Convert to oral 0.125–0.25 mg once daily after stabilization

Maximum dose 1 mg total IV loading in 24 hours

Clinical Notes:

• Does NOT reduce mortality; used for symptom relief and rate control

• Target therapeutic trough level: 0.5–0.9 ng/mL for HFrEF

• Use lower doses (0.125 mg daily or alternate days) for elderly, low body weight, or renal impairment

1. Atrial Fibrillation — Rate Control (particularly in patients with heart failure or sedentary individuals)

A. Oral Route

Parameter Recommendation

Starting dose (Loading) 0.5 mg in divided doses over 24 hours (e.g., 0.25 mg × 2 doses, 6–8 hours apart)

Titration Assess heart rate response after 24–48 hours

Usual maintenance dose 0.125–0.25 mg once daily

Maximum dose 0.25 mg/day for long-term use

B. Intravenous Route

Parameter Recommendation

Starting dose (Loading) 0.25–0.5 mg IV over 15–30 minutes

Titration Additional 0.25 mg IV every 6 hours × 2 doses if needed

Usual maintenance dose Convert to oral therapy once rate controlled

Maximum dose 1 mg total IV loading in 24 hours

Clinical Notes:

• Not first-line monotherapy in active/ambulatory patients or high sympathetic states (exercise, thyrotoxicosis)

• Often combined with beta-blockers or diltiazem for optimal rate control

• Target resting heart rate: <80–90 bpm

Secondary Indications — Adults (Off-label, if any)

Indication Dose Duration Supervision Label Status Evidence Basis

Paroxysmal supraventricular tachycardia (PSVT) — when adenosine, beta-blockers, or CCBs ineffective/contraindicated 0.25–0.5 mg IV single dose; repeat 0.25 mg after 4–6 hours if needed Single episode management Specialist only OFF-LABEL Indian cardiology practice; limited RCT data

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Congestive Heart Failure and Supraventricular Tachyarrhythmias

Digitalizing (Loading) Dose — Give in divided doses over 12–24 hours

Preterm neonates 20–30 mcg/kg total 15–25 mcg/kg total Give 50% initially, then 25% × 2 at 8-hour intervals

Term neonates (0–1 month) 25–35 mcg/kg total 20–30 mcg/kg total Same divided schedule

Infants (1–24 months) 35–60 mcg/kg total 30–50 mcg/kg total Higher doses due to larger volume of distribution

Children (2–10 years) 30–40 mcg/kg total 25–35 mcg/kg total Divide as above

Children (>10 years) 10–15 mcg/kg total OR 0.75–1.5 mg total 8–12 mcg/kg OR 0.5–1 mg total Adult-like dosing

Maintenance Dose

Age Group Oral Maintenance IV Maintenance

Preterm neonates 5–8 mcg/kg/day in 2 divided doses 4–6 mcg/kg/day

Term neonates 8–10 mcg/kg/day in 2 divided doses 6–8 mcg/kg/day

Infants (1–24 months) 10–15 mcg/kg/day in 2 divided doses 8–12 mcg/kg/day

Children (2–10 years) 8–10 mcg/kg/day in 2 divided doses 6–8 mcg/kg/day

Children (>10 years) 2.5–5 mcg/kg/day OR 0.125–0.25 mg/day Same as oral

Age Restrictions:

• NOT recommended below 6 weeks of age except under paediatric cardiology supervision in tertiary care settings

• Avoid IM administration due to severe local pain and erratic absorption

Safety Monitoring:

• Baseline ECG (PR interval, rhythm) and serum electrolytes (K⁺, Mg²⁺, Ca²⁺)

• Therapeutic drug level: 0.8–2.0 ng/mL (levels >2 ng/mL indicate toxicity risk)

• IV administration: give slowly over ≥5 minutes with ECG monitoring

• Monitor heart rate appropriate for age

Secondary Indications — Paediatric Doses (Off-label, if any)

Not applicable.

50 Usual dose; monitor levels periodically

30–50 0.125 mg once daily OR 0.0625 mg twice daily

10–30 0.125 mg every alternate day OR 0.0625 mg once daily

<10 or Dialysis 0.125 mg every 48–72 hours; guide by serum levels

Haemodialysis: Digoxin is NOT efficiently removed (large volume of distribution); no supplemental dose required. Adjust based on pre-dialysis serum levels.

• Ventricular fibrillation

• Ventricular tachycardia (unless heart failure-related and under specialist care)

• Hypersensitivity to digoxin or other digitalis glycosides

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

• Sick sinus syndrome (without functioning pacemaker)

• Hypertrophic obstructive cardiomyopathy (HOCM) with outflow tract obstruction

• Wolff-Parkinson-White (WPW) syndrome with atrial fibrillation

• Known digitalis toxicity

• Severe hypokalaemia or hypercalcaemia (correct before initiating)

• Renal impairment — requires dose reduction and level monitoring

• Electrolyte disturbances (hypokalaemia, hypomagnesaemia, hypercalcaemia) — predispose to toxicity

• Elderly patients — reduced renal clearance and increased sensitivity

• Acute myocardial infarction — may increase oxygen demand and arrhythmia risk

• Thyroid disorders — hypothyroidism increases sensitivity; hyperthyroidism increases resistance

• Cor pulmonale or severe pulmonary disease

• Recent cardioversion — increased sensitivity post-procedure

• Restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis

• Concomitant use of drugs that increase digoxin levels or cause hypokalaemia

Parameter Details

Overall safety Generally considered safe; used when clearly indicated

Placental transfer Yes — crosses placenta; fetal serum levels approximately equal to maternal

Teratogenicity No documented teratogenic risk in humans

When to use Maternal heart failure, atrial fibrillation, or treatment of fetal supraventricular tachycardia

Preferred alternative Digoxin is often the preferred agent for fetal arrhythmias

Monitoring Maternal serum digoxin levels, serum potassium, renal function; fetal heart rate monitoring

Parameter Details

Compatibility Compatible with breastfeeding

Milk levels Low; milk-to-plasma ratio approximately 0.6–0.9

Infant exposure Estimated infant dose <2% of maternal dose — clinically insignificant

Preferred alternative Not required; digoxin is acceptable during lactation

Infant monitoring Observe for unusual drowsiness, feeding difficulties, or poor weight gain (rare)

• Starting dose: 0.125 mg once daily or alternate days

• Titration: Slow; reassess after 1–2 weeks

• Special considerations:

• Age-related decline in renal function increases toxicity risk

• Increased myocardial sensitivity to digitalis effects

• Higher incidence of drug interactions (polypharmacy)

• Lean body mass should guide dosing

• Serum level monitoring strongly recommended

• Watch for neurological toxicity: confusion, visual disturbances, delirium

Interacting Drug Effect Management

Amiodarone Increases digoxin levels by 50–100% (P-gp inhibition, reduced renal clearance) Reduce digoxin dose by 50%; monitor serum levels

Quinidine Increases digoxin levels by 50–100% Reduce digoxin dose by 50%; monitor serum levels

Verapamil Increases digoxin levels by 40–80%; additive AV nodal blockade Reduce digoxin dose by 25–50%; ECG monitoring

Diltiazem Increases digoxin levels by 20–40%; additive AV nodal effects Monitor digoxin levels; ECG surveillance

Dronedarone Increases digoxin levels significantly Reduce digoxin dose by 50%; limit digoxin to ≤0.125 mg/day

Macrolides (erythromycin, clarithromycin) Increase digoxin via P-glycoprotein inhibition and altered gut flora Monitor digoxin levels; consider dose reduction

Potassium-wasting diuretics (furosemide, thiazides) Hypokalaemia potentiates digoxin toxicity Maintain serum K⁺ >4 mEq/L; consider K⁺ supplementation or K⁺-sparing diuretics

Spironolactone Can increase digoxin levels; may interfere with digoxin assay Monitor clinically; use digoxin-specific assay if available

Cyclosporine Increases digoxin levels Monitor digoxin levels closely

Itraconazole/Ketoconazole P-gp inhibition increases digoxin levels Monitor and reduce dose if needed

Interacting Drug Effect Management

Beta-blockers Additive bradycardia and AV nodal block Can be used together; monitor heart rate and ECG

Rifampicin Induces P-gp; reduces digoxin levels by 30–50% Monitor efficacy; may need dose increase

Phenytoin, Carbamazepine May reduce digoxin absorption and increase metabolism Monitor digoxin levels

St John's Wort Reduces digoxin levels (P-gp induction) Avoid concomitant use or monitor closely

Antacids (aluminium/magnesium) May reduce digoxin absorption Separate administration by at least 2 hours

Sucralfate May reduce digoxin absorption Administer digoxin 2 hours before sucralfate

Metoclopramide Increases GI motility; may reduce digoxin absorption Monitor clinical response

NSAIDs May reduce renal clearance of digoxin Monitor renal function and digoxin levels

Propafenone Increases digoxin levels by 30–40% Monitor levels; may need dose reduction

• Nausea, vomiting, anorexia

• Diarrhoea, abdominal discomfort

• Fatigue, weakness

• Headache, dizziness

• Bradycardia (sinus)

• Visual disturbances (blurred vision, yellow-green halos, altered colour perception)

Adverse Effect Clinical Notes

Digoxin toxicity syndrome Nausea, vomiting, confusion, visual changes, cardiac arrhythmias — requires immediate discontinuation and hospitalisation

Ventricular arrhythmias Premature ventricular contractions, bigeminy, ventricular tachycardia, ventricular fibrillation

High-grade AV block Second- or third-degree heart block; may require temporary pacing

Atrial tachycardia with block Pathognomonic of digoxin toxicity

Severe hyperkalaemia In acute massive overdose; life-threatening

Neuropsychiatric effects Confusion, disorientation, hallucinations, psychosis (especially in elderly)

Management of severe toxicity:

• Discontinue digoxin immediately

• Correct electrolyte abnormalities (especially potassium)

• Continuous ECG monitoring

• Digoxin-specific antibody fragments (Fab) — indicated for life-threatening arrhythmias or ingestion >10 mg in adults (availability in India is limited; contact tertiary centre)

Baseline (before initiation):

• Serum creatinine and eGFR

• Serum electrolytes: potassium, magnesium, calcium

• 12-lead ECG

• Body weight (use ideal body weight for dosing in obesity)

• Thyroid function (if clinically indicated)

After initiation or dose change:

• Serum digoxin level: Obtain at least 6–8 hours post-dose (trough preferred); measure after 5–7 days of stable dosing

• Target: 0.5–0.9 ng/mL for heart failure; 0.8–2 ng/mL for AF rate control

• Heart rate and rhythm assessment

• Repeat electrolytes within 1 week if unstable or diuretics co-prescribed

• Clinical assessment for toxicity symptoms

Long-term:

• Serum digoxin levels every 3–6 months, or sooner if:

• Change in renal function

• New interacting drug added

• Clinical features suggestive of toxicity

• Dose adjustment made

• Renal function every 3–6 months (more frequently in elderly)

• Periodic electrolyte monitoring

Brand Name Manufacturer

Lanoxin GSK/Aspen

Cardioxin Cadila

Toloxin Torrent

Digoxin (generic) Multiple manufacturers

Digoxin is included in AIIMS and JIPMER hospital formularies.

Regulatory status: Included in National List of Essential Medicines (NLEM) 2022; price under NPPA regulatory control.

1. Narrow therapeutic index — Small margin between therapeutic and toxic doses; always maintain high vigilance for toxicity signs.

1. Electrolyte correction is mandatory — Never initiate or continue digoxin without ensuring adequate serum potassium and magnesium levels.

1. Lower doses are usually sufficient — Target serum level of 0.5–0.9 ng/mL in heart failure provides benefit without increased mortality; avoid levels >1.2 ng/mL.

1. Avoid routine use in HFpEF — Digoxin has no proven benefit in heart failure with preserved ejection fraction.

1. Toxicity can occur even with "normal" levels — Clinical assessment remains paramount; serum levels do not always correlate with toxicity.

1. Watch for sudden renal decline — Any acute kidney injury can unmask digoxin toxicity; reassess dosing immediately.

1. Drug interaction vigilance — When adding amiodarone, quinidine, or verapamil, pre-emptively reduce digoxin dose by 50%.

heart failure; HFrEF; atrial fibrillation; rate control; digitalis; cardiac glycoside; narrow therapeutic index; renal-dose-adjust; elderly-risk; drug interactions; NLEM India; cardiology

RxIndia v1.0 — 10 May 2025

• CDSCO drug database and approved product inserts

• National List of Essential Medicines (NLEM) 2022

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Formulary

• Cardiological Society of India — Consensus documents on Atrial Fibrillation (2021)

• IAP Drug Formulary (paediatric dosing reference)

• WHO Model Formulary (supportive paediatric reference)

• Harrison's Principles of Internal Medicine (supportive reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (pharmacology reference)