Schedule H

Oral

• Tablet: 0.1 mg

• Injection: NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Congestive Heart Failure (Systolic dysfunction with reduced ejection fraction)

Parameter Dosing Details

Starting dose 0.05–0.1 mg once daily

Titration Increase after 5–7 days based on clinical response and serum digoxin-equivalent levels

Usual maintenance dose 0.1–0.2 mg once daily

Maximum dose 0.2 mg/day (in adults with normal renal function)

Clinical Notes:

• Preferred in patients with coexistent atrial fibrillation with rapid ventricular response

• Use in combination with standard heart failure therapy (ACE inhibitors, beta-blockers, diuretics)

• Maintain serum digoxin-equivalent levels at 0.5–0.9 ng/mL for optimal benefit-risk ratio

• Loading dose usually not required in stable chronic heart failure

1. Atrial Fibrillation (Rate control)

Parameter Dosing Details

Loading dose (if rapid digitalisation needed) 0.4–0.6 mg total over 24 hours in 2–3 divided doses

Starting dose (without loading) 0.1 mg once daily

Titration Adjust based on ventricular rate and tolerance

Usual maintenance dose 0.1–0.2 mg once daily

Maximum dose 0.2 mg/day

Clinical Notes:

• Beta-blockers or non-dihydropyridine calcium channel blockers are first-line for rate control in AF without heart failure

• Methyldigoxin preferred when AF coexists with heart failure with reduced ejection fraction

• Less effective for rate control during exercise compared to beta-blockers

• Loading dose should be individualised based on age, renal function, and body weight

Secondary Indications – Adults (Off-label, if any):

Not applicable. No routinely documented off-label uses in Indian clinical practice.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India):

1. Congestive Heart Failure

Neonates (term) 25–35 mcg/kg divided in 2–3 doses 8–10 mcg/kg/day Divided in 2 doses

Infants (1–24 months) 35–50 mcg/kg divided in 2–3 doses 10–15 mcg/kg/day Divided in 2 doses

Children (2–10 years) 25–40 mcg/kg divided in 2–3 doses 6–10 mcg/kg/day Divided in 2 doses

Children (>10 years) 15–25 mcg/kg divided in 2–3 doses 4–8 mcg/kg/day Once or twice daily

Clinical Notes:

• Always calculate dose based on lean body weight

• Give half the digitalising dose initially, then remaining in 2 divided doses at 6–8 hour intervals

• Monitor ECG before each digitalising dose increment

1. Supraventricular Tachyarrhythmias (including atrial flutter)

• Dose: Same as CHF dosing above

• Duration: As clinically required; often used until rhythm control achieved or rate controlled

• Specialist only: Paediatric cardiology supervision mandatory

Secondary Indications – Paediatric (Off-label, if any):

Not applicable in routine Indian paediatric practice.

Safety Statements:

• Preterm neonates (<37 weeks): NOT recommended without paediatric cardiology supervision; increased sensitivity and toxicity risk

• Minimum age: No absolute minimum; use in neonates only under specialist care

Monitoring in Paediatrics:

• Serum potassium before and during therapy

• ECG monitoring (PR interval, arrhythmias)

• Renal function

• Clinical signs of toxicity: poor feeding, vomiting, lethargy, bradycardia

60 No adjustment required

30–60 Use 50–75% of standard dose

15–30 Use 25–50% of standard dose; avoid loading

<15 or on dialysis Use 25% of standard dose; specialist input essential

Additional Notes:

• Methyldigoxin undergoes significant renal excretion

• Accumulation risk is high in renal impairment

• Monitor digoxin-equivalent levels closely if available

• Not significantly removed by haemodialysis

• Hypersensitivity to methyldigoxin, digoxin, or any digitalis glycoside

• Ventricular fibrillation

• Ventricular tachycardia

• Hypertrophic obstructive cardiomyopathy (unless concurrent AF with rapid ventricular rate)

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

• Sick sinus syndrome without pacemaker

• Wolff-Parkinson-White syndrome with atrial fibrillation (risk of accelerated conduction via accessory pathway)

• Cardiac glycoside toxicity

• Renal impairment (dose accumulation and toxicity risk)

• Elderly patients (increased sensitivity)

• Electrolyte disturbances: hypokalaemia, hypomagnesaemia, hypercalcaemia (potentiate arrhythmogenicity)

• Hypothyroidism (decreased clearance) or hyperthyroidism (increased clearance)

• Acute myocardial infarction (increased arrhythmia risk)

• Myocarditis or severe pulmonary disease (cor pulmonale)

• Electrical cardioversion planned (reduce dose or hold; risk of arrhythmias)

• Concurrent use of drugs increasing digoxin levels (amiodarone, verapamil, macrolides)

• Restrictive cardiomyopathy, constrictive pericarditis, or cardiac amyloidosis

Parameter Details

Safety Limited data; generally considered relatively safe when clearly indicated

Risk category Not formally classified in India; use only if benefit outweighs risk

Indications in pregnancy Maternal atrial fibrillation with heart failure; fetal supraventricular tachycardia (transplacental therapy)

Preferred alternatives Beta-blockers (metoprolol, labetalol) preferred for maternal rate control if suitable

Monitoring Maternal ECG, digoxin-equivalent levels; fetal heart rate monitoring; watch for fetal bradycardia

Parameter Details

Compatibility Generally compatible with breastfeeding

Drug levels in milk Low; relative infant dose estimated <2%

Preferred alternatives None required if clinically indicated

Infant monitoring Observe for feeding difficulties, unusual irritability, or bradycardia (rare)

Parameter Recommendation

Starting dose 0.05 mg once daily

Titration Slow; increase at intervals of 7–14 days

Maximum dose Generally limit to 0.1–0.15 mg/day

Special concerns Reduced renal function (even with normal creatinine), increased sensitivity to toxicity, higher risk of confusion, visual disturbances, falls, and arrhythmias

Note: Avoid loading dose in elderly unless clinically compelling; monitor electrolytes and renal function frequently.

Interacting Drug Effect Management

Amiodarone Increases methyldigoxin levels by 50–100% via P-glycoprotein inhibition and reduced renal clearance Reduce methyldigoxin dose by 50%; monitor levels and ECG

Verapamil Increases levels by 50–75%; additive AV nodal blockade Reduce methyldigoxin dose; monitor for bradycardia

Quinidine Increases levels by up to 100% via reduced clearance and displacement from tissues Halve methyldigoxin dose; avoid combination if possible

Dronedarone Significant increase in digoxin levels Avoid concomitant use

Erythromycin / Clarithromycin Inhibit P-glycoprotein; increase absorption and reduce elimination Use azithromycin as alternative; monitor closely if macrolide essential

Itraconazole / Ketoconazole P-glycoprotein inhibition; increased toxicity risk Monitor levels; consider dose reduction

Ciclosporin Increases digoxin levels Monitor levels closely

Interacting Drug Effect Management

Beta-blockers Additive bradycardia and AV block Use with caution; monitor heart rate and ECG

Diltiazem Modest increase in levels; additive AV block risk Monitor; may need dose reduction

Loop diuretics (furosemide) Hypokalaemia increases toxicity risk Maintain potassium ≥4.0 mEq/L; supplement as needed

Thiazide diuretics Hypokalaemia and hypomagnesaemia Monitor electrolytes; correct deficiencies

Spironolactone May modestly increase digoxin levels; alters potassium balance Monitor potassium and levels

Rifampicin Induces P-glycoprotein; may reduce methyldigoxin efficacy Monitor clinical response; may need dose increase

Antacids (aluminium/magnesium) Reduce oral absorption Administer methyldigoxin 2 hours before or after antacids

Sucralfate Reduces bioavailability Avoid co-administration; separate by at least 2 hours

Propafenone Increases digoxin levels modestly Monitor

NSAIDs May impair renal function; increase toxicity risk Use with caution; monitor renal function

• Nausea, vomiting, anorexia (early signs of toxicity)

• Fatigue, weakness

• Dizziness, headache

• Diarrhoea

• Bradycardia (sinus)

• Visual disturbances: blurred vision, yellow-green halos (xanthopsia)

Adverse Effect Clinical Notes

Digitalis toxicity syndrome Life-threatening arrhythmias, severe GI symptoms, confusion, altered mental status; requires immediate drug cessation

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

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

Severe bradycardia May cause syncope or haemodynamic compromise

Cardiac arrest Especially in overdose or severe toxicity

Gynaecomastia With prolonged use (rare)

Management of toxicity:

• Discontinue drug immediately

• Correct hypokalaemia and hypomagnesaemia

• Atropine for symptomatic bradycardia

• Digoxin-specific antibody fragments (Fab) — limited availability in India; may need to source from major tertiary centres

Phase Parameters

Baseline Serum creatinine, eGFR, electrolytes (K⁺, Mg²⁺, Ca²⁺), ECG (baseline PR interval, rhythm)

After initiation/dose change ECG and clinical assessment for toxicity signs within 5–7 days; digoxin-equivalent level if available

Long-term (chronic therapy) Serum potassium, magnesium every 1–3 months; renal function every 3–6 months; annual ECG; clinical assessment at each visit

Signs to monitor Nausea, anorexia, visual changes, palpitations, bradycardia, confusion (especially in elderly)

Target serum level: Digoxin-equivalent concentration 0.5–0.9 ng/mL (levels >1.2 ng/mL associated with increased mortality)

• Lanitop® (0.1 mg tablet)

• Digicor-M® (0.1 mg tablet)

(Note: Availability may vary by region; confirm with local distributors. Methyldigoxin is less commonly stocked than digoxin in most pharmacies.)

Notes:

• Not listed under NLEM 2022

• Not under NPPA price control

• May not be available in government hospital supplies; digoxin is more commonly stocked

1. Methyldigoxin vs Digoxin: Methyldigoxin has higher oral bioavailability (~80% vs ~70% for digoxin) and slightly faster onset; however, digoxin is far more commonly used in India and has better availability of specific antibody antidote.

1. Toxicity prolonged: Due to longer half-life than digoxin, toxicity manifestations persist longer; requires prolonged monitoring after discontinuation.

1. Electrolytes first: Always correct hypokalaemia and hypomagnesaemia before initiating therapy; these significantly potentiate toxicity.

1. Low therapeutic index: Narrow margin between therapeutic and toxic levels; prefer lower doses (aim for serum digoxin-equivalent <1.0 ng/mL).

1. Limited antidote availability: Digoxin-immune Fab is not widely available in India; exercise extreme caution in borderline cases, elderly, and renal impairment.

1. Modern role is limited: Consider beta-blockers, ivabradine, or sacubitril-valsartan combinations for heart failure; digitalisation is now reserved for selected cases with AF and HFrEF.

Methyldigoxin; cardiac glycoside; digitalis; CHF; atrial fibrillation; rate control; toxicity risk; narrow therapeutic index; renal adjustment; elderly-sensitive; specialist-only paediatric; Cardiology

RxIndia v1.0 — 10 Jan 2025

• CDSCO approved product information

• Indian Pharmacopoeia

• API Textbook of Medicine

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

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• AIIMS Cardiology Treatment Protocols

• IAP Drug Formulary (for paediatric dosing)

• NLEM 2022 (methyldigoxin — not listed)