Atlantic Canada Poison Centre
Antidote Kit Manual
Digoxin Immune Fab
DigiFab®
Digoxin Immune Fab
DigiFab®
ALERT: This item is found in the refrigerator antidote kit.
Indications
- Acute or chronic life-threatening digoxin toxicity (or other cardioactive steroid: digitoxin, plants, toad venom) : tachy or brady arrhythmias, hypotension, hyperkalemia (greater than 5 mEq/L) and/or a digoxin serum level of greater than 12.8 nmol/L (greater than 10 ng/mL).
Dosage
ACUTE toxicity
Empiric Dosing (Unknown level and severe toxicity)
- Cardiac arrest imminent or present: 10 vials by direct IV, repeat 5 - 10 vials as needed for ongoing toxicity, after 3 - 5 min. If full amount not available, give closest amount available.
- With hemodynamic compromise: Give 2-4 vials over 30 minutes by IV infusion. Repeat if needed for ongoing toxicity.
Amount Ingested Known:
| Dose (in vials)* = | amount digoxin ingested (mg) x 0.8 x 2 |
*Note: Round up to the next highest number of vials.
Digoxin Level Known:
| Dose (in vials)* = | serum concentration (nmol/L) x 0.781 x patient weight (kg) |
| 100 |
*Note: Round up to the next highest number of vials.
Digoxin levels done greater than 6 hours post dose more accurately reflect toxicity. Serum levels done prior to 6 hours can still be used to calculate dose but may overestimate the dose required.
Or Use Following Table
|
Infant and Small Children Dose Estimates of DIGOXIN IMMUNE FAB (in mg) from Steady-State Serum Digoxin Concentration |
|
Serum Digoxin Concentration (nmol/L) |
|
Weight (kg) |
1 nmol/L |
2 nmol/L |
4 nmol/L |
8 nmol/L |
12 nmol/L |
16 nmol/L |
20 nmol/L |
25 nmol/L |
|
1 kg |
0.3 mg* |
0.6 mg* |
1.2 mg* |
2.5 mg* |
4 mg |
5 mg |
6 mg |
8 mg |
|
3 kg |
1 mg* |
2 mg* |
4 mg |
8 mg |
11 mg |
15 mg |
18 mg |
23 mg |
|
5 kg |
1.5 mg* |
3 mg* |
6 mg |
12 mg |
18 mg |
24 mg |
30 mg |
38 mg |
|
10 kg |
3 mg* |
6 mg |
12 mg |
24 mg |
36 mg |
48 mg |
60 mg |
75 mg |
|
20 kg |
6 mg |
12 mg |
24 mg |
48 mg |
72 mg |
95 mg |
119 mg |
149 mg |
* Dilution of reconstituted vial to 2 mg/mL may be desirable (See Administration; Infusion)
Additional Dosing: For hours to days AFTER Digoxin Immune Fab is given, digoxin levels are clinically meaningless and should NOT guide decisions around further antidote treatment, as they can be falsely elevated. After discussion with the poison centre, additional doses of Digoxin Immune Fab may be given if response was inadequate (i.e. continued toxicity such as arrhythmias, unstable vital signs).
CHRONIC toxicity
Administer one vial at a time over 30 minutes by IV infusion. Repeat if needed.
Administration
- Reconstitution: Reconstitute each vial with 4 mL of sterile water for a final concentration of 10 mg/mL DigiFab®
- IV Direct: If cardiac arrest is imminent, may administer dose undiluted.
- For infants and small children it is recommended that the 40 mg vial be reconstituted as directed above and administered with a tuberculin syringe.
- Blood pressure monitoring, cardiac monitoring and monitoring of potassium levels is required.
- IV Intermittent Infusion: The reconstituted solution (10 mg/ml) should be given by IV infusion over 30 minutes using an infusion pump. Further dilution is not required except for very small doses (less than 4mg)
- Administer dose over 30 minutes. Blood pressure monitoring, cardiac monitoring and monitoring of potassium levels is required.
- For doses less than 4mg, a reconstituted vial can be further diluted with sodium chloride 0.9% to a final concentration of 2 mg/mL prior to administration: add 4mL of the 10 mg/mL DigiFab® solution to 16 mL of sodium chloride 0.9% for a total volume of 20 mL. Discard volume not required for dose.
MONITORING
- Vital signs, EKG, serum potassium
- Digoxin level to be drawn BEFORE administration of antidote only
- Improvement in signs and symptoms of digoxin toxicity typically begins within one half hour or less following digoxin immune Fab administration. Maximum effect within 4 hours.
- Monitor for fluid overload in pediatric patients.
THERAPEUTIC ENDPOINT: Adequate clinical response (stable EKG and vital signs).
- Dose varies according to the amount of digoxin to be neutralized. One 40mg vial of DigiFab® will neutralize approximately 0.5 mg (500 mcg) of digoxin.
- Partial treatment is acceptable if full amount is not available. Contact nearest Emergency Department for additional stock if needed.
Compatibility, Stability
- Compatible with sodium chloride 0.9%. Refrigerate unopened vials. Reconstituted vials are stable for 4 hours in refrigerator.
Potential Hazards of Administration
- Allergic reactions (rare) or febrile reactions. Patients allergic to sheep protein, those who have previously received sheep antibodies or Fab fragments, those with allergies to papain, chymopapain, papaya, other papaya extracts or the pineapple enzyme bromelain may be at risk for allergic or anaphylactic reaction.
- Hypokalemia.
- Worsening of underlying condition (e.g.; atrial fibrillation, congestive heart failure).
Miscellaneous
- It is not necessary to bind the total body digoxin load to control toxicity. The administration of less than the calculated dose of digoxin immune Fab may still be sufficient.
- Digoxin Immune Fab will interfere with digitalis immunoassay measurements so the reported serum digoxin concentration may be misleading until Fab fragments are eliminated from the body. Elimination depends on kidney function.
- 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.
- Digoxin Immune Fab is derived from specific antidigoxin antibodies produced in sheep.
References…
Bailey, B., Blais, R., Gaudreault, P., Gosselin, S., & Laliberte, M. (2009). Antidotes en toxicologie d'urgence (3rd ed.). Quebec, Canada: Centre antipoison du Quebec.
Bauman, J. L., DiMomenico, R. J., & Galanter, W. L. (2006). Mechanisms, manifestations, and management of digoxin toxicity in the modern era. American Journal of Cardiovascular Drugs, 6(2), 77-86.
BTG International Incorporation. (May 2011). Digifab: Product monograph.
GlaxoSmithKline Australia PTY LTD. (October 2008). Digibind: Package insert
Goldfrank, L. R., Nelson, L. S., Lewin, N. A., Howland, M. A., Hoffman, R. S., (2015). Goldfrank's toxicologic emergencies(Tenth ed.). New York: McGraw Hill.
Manini, A. F., Nelson, L. S., & Hoffman, R. S. (2011). Prognostic utility of serum potassium in chronic digoxin toxicity: A case-control study. American Journal of Cardiovascular Drugs, 11(3), 173-178.
Micromedex, T. H. A. (2014). Micromedex health care systems. Retrieved from http://www.micromedexsolutions.com
Olson, K. R. (2007). Poisoning & drug overdose (Sixth ed.). New York: McGraw Hill.
Phelps SJ, C. C. (2013). Teddy bear, pediatric injectable drugs. Retrieved from http://www.pharmpress.com/product/MC_PED/pediatric-injectable-drugs
Shannon, M. W., Borron, S. W., & Burns, M. J. (2007). Haddad and Winchester's clinical management of poisoning and drug overdose (Fourth ed.). Philadelphia: Saunders Elsevier.
Thacker, D., & Sharma, J. (2007). Digoxin toxicity. Clinical Pediatrics, 46(3), 276-279.
Yang, E. H., Shah, S., & Criley, J. M. (2011). Digitalis toxicity: A fading but crucial complication to recognize. American Journal of Medicine, 125(4), 337-343.