Key points
- It is recommended to contact your poison centre in digoxin or cardiac glycosides poisonings potentially requiring digoxin-specific antibodies.
- Hyperkalemia can be caused by acute digitalis intoxication, but it can also be present in chronic toxicity due to the deterioration of renal function. In either case, calcium is not recommended.
- Most standard immunoassays for digoxin will measure both antibody-bound digoxin (inactivated) and free digoxin (active) therefore serum digoxin levels drawn during or after antidote administration are often "falsely" very elevated and uninterpretable. Note: many American-based references use ng/ml instead of nmol/L (1 ng/ml = 1.281 nmol/L).
- On average, onset of action occurs within 20 min and reaches its maximum effect in 4 hours.
- The rate of antidote administration (direct IV or slow IV infusion over 30 min.) is determined by the urgency of the situation (imminent cardiac arrest or not).
+ Synonyms and other terms
- Anti-digoxin antibodies
- Digibind®
- DigiFab®
- Digoxin-specific antibody fragments
- Digoxin immune fab
+ Indications
Digoxin-specific antibodies are indicated in cases of potentially lethal intoxication with digoxin or other substances containing cardiac glycosides (plants, digitoxin, bufo toad venom, etc.) :
- Symptomatic and progressive bradyarrhythmia
- 2nd or 3rd degree atropine-resistant AV block
- Tachycardia or ventricular fibrillation
- Digoxin concentration greater than 12.8 nmol/L more than 6 hours following acute ingestion without cardiotoxic coingestion for asymptomatic or midly symptomatic patients.
- Hyperkalemia equal or greater than 5 mmol/L in acute exposure
Consider administering digoxin-specific antibodies for mixed intoxication involving other cardiotoxic agents (e.g., calcium-channel blocker, beta blocker) even if the digitalis intoxication does not seem very severe, particularly if the administration of calcium is being considered.
+ Dosage
+ Pediatric Dose
*Pediatric Dose (less than 20 kg)
Digoxin level obtained 6 hours or more after ingestion should be used for the calculation of the number of vials using the formulas below.
Acute Intoxication
- Cardiac arrest imminent or present :
- Administer 10 vials direct IV
- Repeat using 5 - 10 vials as needed, after 3 - 5 min.
- With hemodynamic compromise :
- Administer the number of vials obtained with the following formulas. Select the right formula according to the units you use :
- International units (nmol/L)
- Dose (theoretical number of vials) = digoxin level [nmol/L] x 0.00781) x weight (kg). (Round up to the next highest number of vials)
- Imperial units (ng/mL)
- Dose (theoretical number of vials) = [digoxin level (ng/mL) x weight (kg)] ÷100. (Round up to the next highest number of vials)
- In the event of imminent cardiac arrest, administer direct IV. Otherwise, administer over 30 min.
- International units (nmol/L)
- If a digoxin level taken 6 hours or more after the exposure cannot be obtained:
- Administer 2 - 4 vials to be repeated every 15 - 30 min, as needed. IV infusion over 30 min.
- Administer the number of vials obtained with the following formulas. Select the right formula according to the units you use :
- Without hemodynamic compromise :
- Administer 25% of the dose obtained using the formula, rounded up to complete vial (i.e 2.3 vials → give 3 vials).
- Titrate based on patient response until the total dose calculated has been reached, administering every 30 min.
- IV infusion over 30 min.
Chronic Intoxication
- Administer one vial at a time in consultation with your poison centre.
- Administer one vial by IV over 30 min. Repeat if needed.
For intoxications involving digitalis derivatives other than digoxin: consult your poison centre.
+ Adult Dose
Adult Dose (over 20 kg)
Digoxin level obtained 6 hours or more after ingestion should be used for the calculation of the number of vials using the formulas below.
Acute Intoxication
- Cardiac arrest imminent or present :
- Administer 10 vials direct IV
- Repeat using 5 - 10 vials as needed, after 3 - 5 min.
- With hemodynamic compromise :
- Administer the number of vials obtained with the following formulas. Select the right formula according to the units you use :
- International units (nmol/L):
- Dose (theoretical number of vials) = digoxin level [nmol/L] x 0.00781) x weight (kg). (Round up to the next highest number of vials)
- Imperial units (ng/mL):
- Dose (theoretical number of vials) = [digoxin level (ng/mL) x weight (kg)] ÷100. (Round up to the next highest number of vials)
- In the event of imminent cardiac arrest, administer direct IV. Otherwise, administer over 30 min.
- International units (nmol/L):
- If a digoxin level taken 6 hours or more after the exposure cannot be obtained:
- Administer 2 - 4 vials to be repeated every 15 - 30 min, as needed. IV infusion over 30 min.
- Administer the number of vials obtained with the following formulas. Select the right formula according to the units you use :
- Without hemodynamic compromise :
- Administer 25% of the dose obtained using the formula, rounded up to complete vial (i.e 2.3 vials → give 3 vials).
- Titrate based on patient response until the total dose calculated has been reached, administering every 30 min.
- IV infusion over30 min.
Chronic Intoxication
- Administer one vial at a time in consultation with your poison centre.
- Administer one vial by IV over30 min. Repeat if needed.
For intoxications involving digitalis derivatives other than digoxin: consult the poison centre.
+ Renal Impairment
- The half-life is 15 to 20 hours in patients with normal renal function and appears to be up to 10 times longer in patients with renal impairment, even though the volume of distribution remains unchanged. If renal impairment is severe, the drug will be slowly eliminated by the reticuloendothelial system.
- Even so, no data suggests that the dose should be modified for short-term use.
+ Hepatic Impairment
No data suggests that the dose should be modified for short-term use.
+ Hemodialysis Patient
- FAB - digoxin antibody complex is slightly dialyzable, however, extracorporeal treatment is not recommended.
- No data suggests that the dose should be modified for short-term use.
+ Pregnancy
- The safety of digoxin-specific antibodies have not been demonstrated.
- Do not hesitate to use during pregnancy if the anticipated toxic effects pose a significant risk of morbidity or mortality.
- No data suggests that the dose should be modified for short-term use.
+ Obese or Overweight Patient
- No data suggests that the dose should be modified for short-term use.
- Maximum dosing weight provided in product monograph is 100 kg; no maximum dose specified.
+ Adverse effects
- Hypokalemia (especially in the first four hours of treatment).
- Tachycardia (especially if atrial fibrillation)
- Exacerbation of pre-existing heart failure
- Allergic reaction (rare)
+ Monitoring
- Vital signs
- EKG
- Serum potassium
- Digoxin level BEFORE administration of antidote only unless you have access to free digoxin levels.
- Most standard immunoassays for digoxin will measure both antibody-bound digoxin (inactivated) and free digoxin (active) therefore serum digoxin levels drawn during or after antidote administration are often "falsely" very elevated and uninterpretable. Note: many American-based references use ng/ml instead of nmol/L (1 ng/ml = 1.281 nmol/L).
+ End of treatment
- Adequate clinical response: Stable EKG and vital signs.
- Total absence of response after first dose when diagnosis is uncertain.
- No relapse of toxicity 6 - 12 hours after administration of DigiFab, especially if the dose administered was lower than the theoretical dose.
- For patients with severe renal impairment, recurrence of toxicity may occur later and more than 48 hours after administration. Contact your poison centre for the observation period of these patients.
+ Special Notes on Administration
Intravenous Route (IV)
- In newborns and young children requiring low doses, administer the undiluted content with a tuberculin syringe. For very low doses, it is best to dilute the content of the reconstituted vial with 36 ml of NS to obtain a final concentration of 1 mg/ml.
- In contrast to Digibind, administration of DigiFab does not require the use of a 0.22 micron filter.
- Direct IV :
- Only in very urgent situations (imminent cardiac arrest) and with the treating physician at the patient’s bedside.
- The reconstituted 10 mg/ml solution can be administered by direct IV over 2 to 3 min.
- Slow IV Infusion over 30 min :
- The reconstituted 10 mg/ml solution is administered by slow IV infusion over 30 min using a volumetric pump.
- For low doses, the antidote can be diluted in NS to a final concentration of 1 to 10 mg/ml to facilitate its administration.
Subcutaneous Route (SC)
- No data available.
Intramuscular Route (IM)
- No data available.
Intraosseous Route (IO)
- No data available.
Reconstitution
DigiFab: 40 mg /vial:
- Each 40-mg vial must be reconstituted with 4 ml of sterile water for injection.
- Mix gently, rolling between hands until complete dissolution to avoid the formation of bubbles.
- The final solution should be clear and colourless.
- A reconstituted vial of digoxin-specific antibodies provides a total volume of 4 ml at a concentration of 10 mg/ml.
Compatibility
Partial list only. Consult the pharmacist on duty at your health care facility.
- Compatible solutions : SWFI, NS.
- Y-site compatibility : No data available.
- Y-site incompatibility : No data available.
Stability
- Stores unreconstituted vials in the refrigerator at a temperature between 2°C and 8°C.
- Vials are stable for 4 hours after reconstitution.
+ Available products
- DigiFab, 40 mg/vial, Pd. Inj., distributed by Innomar Strategies, DIN 02361043,
- Direct order from Innomar Strategies:
- Phone number: 1-844-233-7167
- Fax number: 1-844-435-9677
- E-mail address: customeservice@innomar-strategies.com
- Product code: DR001611
- Minimum quantity to place an order: 4 vials
- Direct order from Innomar Strategies:
+ Amount required to treat a person weighting 70kg during 24 hours
- At least 20 vials.
+ References
Chan, B. S. H., and N. A. Buckley. 2014. “Digoxin-Specific Antibody Fragments in the Treatment of Digoxin Toxicity.” Clinical Toxicology 52 (8). Taylor & Francis:824–36.
Chan, Betty S., Geoffrey K. Isbister, Margaret O’Leary, Angela Chiew, and Nicholas A. Buckley. 2016. “Efficacy and Effectiveness of Anti-Digoxin Antibodies in Chronic Digoxin Poisonings from the DORA Study (ATOM-1).” Clinical Toxicology 54 (6):488–94.
Chhabra, Neeraj, Matthew Valento, Sean M. Bryant, and Steven E. Aks. 2016. “Digoxin-Specific Antibody Fragment Dosing: A Case Series.” American Journal of Therapeutics 23 (6):e1597–1601.
Mégarbane, Bruno. 2017. “Anti-Digoxin-Specific Fab Fragments.” In Critical Care Toxicology, edited by Jeffrey Brent, Keith Burkhart, Paul Dargan, Benjamin Hatten, Bruno Megarbane, Robert Palmer, and Julian White, 125:1–10. Cham: Springer International Publishing.
Roberts, Darren M., Gamini Gallapatthy, Asunga Dunuwille, and Betty S. Chan. 2016. “Pharmacological Treatment of Cardiac Glycoside Poisoning.” British Journal of Clinical Pharmacology 81 (3):488–95.
Ujhelyi, M. R., and S. Robert. 1995. “Pharmacokinetic Aspects of Digoxin-Specific Fab Therapy in the Management of Digitalis Toxicity.” Clinical Pharmacokinetics 28 (6):483–93.
Zuckerman, Matthew, Howard A. Greller, and Kavita M. Babu. 2015. “A Review of the Toxicologic Implications of Obesity.” Journal of Medical Toxicology: Official Journal of the American College of Medical Toxicology 11 (3):342–54.
James B. Mowry et al, Extracorporeal treatment for digoxin poisoning: systematic review and recommendations from the EXTRIP Workgroup, Clinical Toxicology, 2016, 54:2, 103-114
