Schedule H

Intravenous

• Lyophilized powder for injection: 40 mg per vial (each vial neutralizes approximately 0.5 mg of digoxin)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Life-threatening Digoxin Toxicity or Overdose

Includes:

• Ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation)

• Bradyarrhythmias with haemodynamic compromise unresponsive to atropine

• Hyperkalaemia (>5.5 mmol/L) in setting of digoxin toxicity

• Cardiac arrest attributed to digoxin toxicity

Dose Calculation Methods:

Clinical Scenario Dose Calculation Formula

Known quantity of digoxin ingested (acute) Number of vials = Amount ingested (mg) × 1.6

Known steady-state serum digoxin level Number of vials = [Serum digoxin (ng/mL) × Body weight (kg)] ÷ 100

Empiric Dosing (when ingested amount and serum level unknown):

Severity Dose

Cardiac arrest / Life-threatening arrhythmia 10–20 vials IV

Severe toxicity (haemodynamically unstable) 10 vials IV

Moderate toxicity (stable but symptomatic) 3–6 vials IV

Administration:

• Reconstitution: Add 4 mL sterile water for injection to each vial

• Dilution: Further dilute in 50–100 mL normal saline

• Infusion rate: Administer over 30 minutes

• Cardiac arrest: May give as rapid IV bolus

• Repeat dosing: Additional vials may be given based on clinical response; reassess after 30–60 minutes

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

Not documented in Indian practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indication: Life-threatening Digoxin Toxicity

Dose Calculation (same principles as adults):

Clinical Scenario Dose Calculation

Known quantity ingested Number of vials = Amount ingested (mg) × 1.6

Known serum digoxin level (steady-state) Number of vials = [Serum digoxin (ng/mL) × Body weight (kg)] ÷ 100

Empiric Dosing (when above values unavailable):

Weight Category Empiric Dose

< 20 kg 1 vial

20–40 kg 1–2 vials

40 kg 3–6 vials

Safety Monitoring:

• Continuous cardiac monitoring mandatory

• Serial serum potassium measurement

• Avoid relying on serum digoxin levels for 3–5 days post-Fab (falsely elevated due to assay interference)

Minimum Age Limit:

• No lower age limit established

• May be used in neonates and infants under paediatric intensivist/toxicologist supervision

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

Not documented in Indian specialist guidelines

Note: Renal impairment may prolong elimination of Fab-digoxin complexes, but free digoxin remains neutralized. Monitor for delayed rebound toxicity in severe renal failure.

Note: Fab fragments undergo proteolytic degradation; hepatic metabolism is not a significant elimination pathway.

• Known hypersensitivity to ovine (sheep) proteins

• Known hypersensitivity to papain or papaya (cross-reactivity due to manufacturing process)

• Elevated serum digoxin level without clinical evidence of toxicity (high level alone is NOT an indication)

• Pre-existing hypokalaemia — correct before or concurrent with Fab administration; risk of severe hypokalaemia post-neutralization

• Pre-existing heart failure dependent on digoxin effect — may decompensate after reversal

• Renal impairment — prolonged clearance of Fab-digoxin complexes; monitor for delayed rebound

• Atopic individuals or history of allergic reactions — increased anaphylaxis risk

• Ensure resuscitation equipment and adrenaline available before administration

• Re-digitalization should be delayed for several days after Fab therapy

Parameter Details

Overall safety No contraindication when clinically indicated for life-threatening toxicity

Risk to fetus Fab fragments are large molecules; unlikely to cross placenta significantly

Preferred alternatives None — Fab therapy is the definitive treatment for severe digoxin toxicity

When to use Always use if maternal life at risk; benefit clearly outweighs theoretical risk

Monitoring Continuous fetal heart rate monitoring if mother haemodynamically unstable; post-resuscitation obstetric evaluation

Parameter Details

Compatibility Not contraindicated during breastfeeding

Transfer to milk Fab fragments unlikely to be present in milk at significant levels due to large molecular size

Oral absorption by infant Not absorbed orally; no systemic effect expected

Preferred alternatives Not applicable — emergency antidote

Infant monitoring General feeding behaviour and wellbeing

• No specific dose adjustment required

• Higher baseline risk of digoxin toxicity due to reduced renal clearance — may require Fab therapy more frequently

• Calculate dose based on actual clinical severity; empiric dosing should be used cautiously

• Monitor closely for hypokalaemia and rebound toxicity

• Pre-existing cardiac conditions may mask or complicate clinical response

Interacting Agent Effect Recommendation

Other cardiac glycosides (oleander, yellow oleander poisoning — bufadienolides) Cross-reactivity possible but unpredictable; Fab may partially bind plant glycosides Consider higher doses; consult toxicologist

Digoxin re-administration Fab fragments may still be present, binding and inactivating newly administered digoxin Avoid re-digitalization for minimum 5–7 days after Fab therapy

Not applicable — Digoxin immune Fab is used as acute antidote therapy; no clinically relevant moderate drug interactions documented.

• Hypokalaemia (due to rapid intracellular potassium shift when digoxin effect reversed)

• Fever and chills during or after infusion

• Infusion site reactions (pain, erythema, phlebitis)

• Nausea

Adverse Effect Clinical Notes

Anaphylaxis Rare; higher risk with prior sheep protein or papain allergy; immediate discontinuation and adrenaline required

Serum sickness Delayed hypersensitivity reaction; may occur 7–14 days post-infusion; presents with fever, arthralgia, rash

Rebound digoxin toxicity May occur if Fab clears before all digoxin eliminated; more common in renal impairment

Acute pulmonary oedema Rare; may occur in patients with heart failure dependent on digoxin for rate control or inotropy

Worsening heart failure Due to loss of digoxin's positive inotropic effect

Phase Parameters

Baseline ECG, serum potassium, serum digoxin level (if available), renal function, vital signs

During infusion Continuous cardiac monitoring, blood pressure, watch for infusion reactions or anaphylaxis

After administration ECG monitoring for minimum 6 hours post-infusion; serum potassium every 4–6 hours for 24 hours; clinical reassessment at 30–60 minutes for need of additional doses

Long-term Not applicable — single-use antidote; note that serum digoxin assays will be unreliable for 3–5 days post-Fab due to assay interference

• DigiFab® (BTG/Pfizer) — CDSCO-approved imported product

• DigiBind® — previously available; currently limited or unavailable in Indian market

Note: Limited availability; typically stocked only in major tertiary care centres with toxicology or cardiac intensive care units. Advance procurement may be necessary.

Product Approximate Cost

• Not included in NLEM

• Not under NPPA price control

• High cost; availability primarily in tertiary care emergency settings

• Government supply: NOT AVAILABLE in standard government supply chains

1. Rapid onset of action — clinical improvement in arrhythmias typically seen within 30–60 minutes of administration

1. Do not rely on post-Fab digoxin levels — total serum digoxin concentration remains falsely elevated for 3–5 days due to assay cross-reactivity with Fab-bound digoxin; only free digoxin levels (rarely available) are reliable

1. Anticipate hypokalaemia — digoxin toxicity causes potassium to shift extracellularly; once digoxin is neutralized, potassium rapidly re-enters cells; be prepared to supplement potassium

1. Conservative empiric dosing in stable patients — dose calculations often overestimate need; in non-arrest situations, start with lower empiric doses and reassess

1. Avoid early re-digitalization — Fab fragments persist in circulation; newly administered digoxin will be bound and inactivated for several days

1. Consider in plant cardiac glycoside poisoning — may have partial efficacy in yellow oleander (Thevetia peruviana) or common oleander poisoning, though cross-reactivity is incomplete; specialist consultation recommended

Digoxin immune fab; digoxin toxicity; cardiac glycoside poisoning; antidote; Fab fragment; arrhythmia emergency; hyperkalaemia; emergency medicine; toxicology; paediatric-specialist; renal-safe

RxIndia v1.0 — 15 May 2024

• CDSCO Import Drug Database

• Indian Pharmacopoeia

• AIIMS Emergency Medicine Protocols

• API Textbook of Medicine — Cardiology and Clinical Toxicology sections

• Harrison's Principles of Internal Medicine

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Published Indian case reports on digitalis and oleander poisoning management