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DIGIBIND (digoxin immune fab) , Digoxin Immune Fab (Ovine), is indicated for treatment of potentially life-threatening digoxin intoxication.3 Although designed specifically to treat life-threatening digoxin overdose, it has also been used successfully to treat life-threatening digitoxin overdose.3 Since human experience is limited and the consequences of repeated exposures are unknown, DIGIBIND (digoxin immune fab) is not indicated for milder cases of digitalis toxicity.
Manifestations of life-threatening toxicity include severe ventricular arrhythmias such as ventricular tachycardia or ventricular fibrillation, or progressive bradyarrhythmias such as severe sinus bradycardia or second or third degree heart block not responsive to atropine.
Ingestion of more than 10 mg of digoxin in previously healthy adults or 4 mg of digoxin in previously healthy children, or ingestion causing steady-state serum concentrations greater than 10 ng/mL, often results in cardiac arrest. Digitalis-induced progressive elevation of the serum potassium concentration also suggests imminent cardiac arrest. If the potassium concentration exceeds 5 mEq/L in the setting of severe digitalis intoxication, therapy with DIGIBIND (digoxin immune fab) is indicated.
DOSAGE AND ADMINISTRATION
General Guidelines: The dosage of DIGIBIND (digoxin immune fab) varies according to the amount of digoxin (or digitoxin) to be neutralized. The average dose used during clinical testing was 10 vials.
Dosage for Acute Ingestion of Unknown Amount: Twenty (20) vials (760 mg) of DIGIBIND (digoxin immune fab) is adequate to treat most life-threatening ingestions in both adults and children. However, in children it is important to monitor for volume overload. In general, a large dose of DIGIBIND (digoxin immune fab) has a faster onset of effect but may enhance the possibility of a febrile reaction. The physician may consider administering 10 vials, observing the patient's response, and following with an additional 10 vials if clinically indicated.
Dosage for Toxicity During Chronic Therapy: For adults, six vials (228 mg) usually is adequate to reverse most cases of toxicity. This dose can be used in patients who are in acute distress or for whom a serum digoxin or digitoxin concentration is not available. In infants and small children ( ≤ 20 kg) a single vial usually should suffice.
Methods for calculating the dose of DIGIBIND (digoxin immune fab) required to neutralize the known or estimated amount of digoxin or digitoxin in the body are given below (see Dosage Calculation section).
When determining the dose for DIGIBIND (digoxin immune fab) , the following guidelines should be considered:
- Erroneous calculations may result from inaccurate estimates of the amount of digitalis ingested or absorbed or from nonsteady-state serum digitalis concentrations. Inaccurate serum digitalis concentration measurements are a possible source of error. Most serum digoxin assay kits are designed to measure values less than 5 ng/mL. Dilution of samples is required to obtain accurate measures above 5 ng/mL.
- Dosage calculations are based on a steady-state volume of distribution of approximately 5 L/kg for digoxin (0.5 L/kg for digitoxin) to convert serum digitalis concentration to the amount of digitalis in the body. The conversion is based on the principle that body load equals drug steady-state serum concentration multiplied by volume of distribution. These volumes are population averages and vary widely among individuals. Many patients may require higher doses for complete neutralization. Doses should ordinarily be rounded up to the next whole vial.
- If toxicity has not adequately reversed after several hours or appears to recur, readministration of DIGIBIND (digoxin immune fab) at a dose guided by clinical judgment may be required.
- Failure to respond to DIGIBIND (digoxin immune fab) raises the possibility that the clinical problem is not caused by digitalis intoxication. If there is no response to an adequate dose of DIGIBIND (digoxin immune fab) , the diagnosis of digitalis toxicity should be questioned.
Acute Ingestion of Known Amount: Each vial of DIGIBIND (digoxin immune fab) contains 38 mg of purified digoxin-specific Fab fragments which will bind approximately 0.5 mg of digoxin (or digitoxin). Thus one can calculate the total number of vials required by dividing the total digitalis body load in mg by 0.5 mg/vial (see Formula 1).
For toxicity from an acute ingestion, total body load in milligrams will be approximately equal to the amount ingested in milligrams for digoxin capsules and digitoxin, or the amount ingested in milligrams multiplied by 0.80 (to account for incomplete absorption) for digoxin tablets.
Table 1 gives dosage estimates in number of vials for adults and children who have ingested a single large dose of digoxin and for whom the approximate number of tablets or capsules is known. The dose of DIGIBIND (digoxin immune fab) (in number of vials) represented in Table 1 can be approximated using the following formula:
|Formula 1: Dose (in # of vials) =||Total digitalis body load in mg|
|0.5 mg of digitalis bound/vial|
Table 1. Approximate Dose of DIGIBIND (digoxin immune fab) for Reversal of a Single
Large Digoxin Overdose
|Number of Digoxin Tablets or Capsules Ingested*||Dose of DIGIBIND # of Vials|
|* 0.25 mg tablets with 80% bioavailability or 0.2 mg LANOXICAPS® Capsules with 100% bioavailability.|
Calculations Based on Steady-State Serum Digoxin Concentrations: Table 2 gives dosage estimates in number of vials for adult patients for whom a steady-state serum digoxin concentration is known. The dose of DIGIBIND (digoxin immune fab) (in number of vials) represented in Table 2 can be approximated using the following formula:
|Formula 2: Dose (in # of vials) =||(Serum digoxin concentration in ng/mL) (weight in kg)|
Table 2. Adult Dose Estimate of DIGIBIND (digoxin immune fab) (in # of vials)
from Steady-State Serum Digoxin Concentration
|Patient Weight||Serum Digoxin Concentration (ng/mL)|
|40||0.5 V||1 V||2 V||3 V||5 V||7 V||8 V|
|60||0.5 V||1 V||3 V||5 V||7 V||10 V||12 V|
|70||1 V||2 V||3 V||6 V||9 V||11 V||14 V|
|80||1 V||2 V||3 V||7 V||10 V||13 V||16 V|
|100||1 V||2 V||4 V||8 V||12 V||16 V||20 V|
|V = vials|
Table 3 gives dosage estimates in milligrams for infants and small children based on the steady-state serum digoxin concentration. The dose of DIGIBIND (digoxin immune fab) represented in Table 3 can be estimated by multiplying the dose (in number of vials) calculated from Formula 2 by the amount of DIGIBIND (digoxin immune fab) contained in a vial (38 mg/vial) (see Formula 3). Since infants and small children can have much smaller dosage requirements, it is recommended that the 38-mg vial be reconstituted as directed and administered with a tuberculin syringe. For very small doses, a reconstituted vial can be diluted with 34 mL of sterile isotonic saline to achieve a concentration of 1 mg/mL.
Formula 3: Dose (in mg) = (Dose [in # of vials]) (38 mg/vial)
Table 3. Infants and Small Children Dose Estimates of DIGIBIND (digoxin immune fab)
(in mg) from Steady-State Serum Digoxin Concentration
|Patient Weight||Serum Digoxin Concentration (ng/mL)|
|1||0.4* mg||1* mg||1.5* mg||3* mg||5 mg||6 mg||8 mg|
|3||1* mg||2* mg||5 mg||9 mg||14 mg||18 mg||23 mg|
|5||2* mg||4 mg||8 mg||15 mg||23 mg||30 mg||38 mg|
|10||4 mg||8 mg||15 mg||30 mg||46 mg||61 mg||76 mg|
|20||8 mg||15 mg||30 mg||61 mg||91 mg||122 mg||152 mg|
|*Dilution of reconstituted vial to 1mg/mL may be desirable.|
Calculation Based on Steady-State Digitoxin Concentration: The dose of DIGIBIND (digoxin immune fab) for digitoxin toxicity can be approximated using the following formula:
|Formula 4: Dose (in # of vials) =||(Serum digitoxin concentration in ng/mL) (weight in kg)|
If the dose based on ingested amount differs substantially from that calculated from the serum digoxin or digitoxin concentration, it may be preferable to use the higher dose.
The contents in each vial to be used should be dissolved with 4 mL of Sterile Water for Injection, by gentle mixing, to give a clear, colorless, approximately isosmotic solution with a protein concentration of 9.5 mg/mL. Reconstituted product should be used promptly. If it is not used immediately, it may be stored under refrigeration at 2° to 8°C (36° to 46°F) for up to 4 hours. The reconstituted product may be diluted with sterile isotonic saline to a convenient volume. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
DIGIBIND, Digoxin Immune Fab (Ovine), is administered by the intravenous route over 30 minutes. It is recommended that it be infused through a 0.22-micron membrane filter to ensure no undissolved particulate matter is administered. If cardiac arrest is imminent, it can be given as a bolus injection.
Vials containing 38 mg of purified lyophilized digoxin-specific Fab fragments. Box of 1 (NDC 0173-0230-44).
Refrigerate at 2° to 8°C (36° to 46°F). Unreconstituted vials can be stored at up to 30°C (86°F) for a total of 30 days.
3. Smith TW, Butler VP Jr, Haber E, Fozzard H, Marcus FI, Bremner WF, Schulman IC, Phillips A. Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments: Experience in 26 cases. N Engl J Med. 1982; 307:1357-1362.
Manufactured by: GlaxoSmithKline, SpA Parma, Italy. Distributed by: GlaxoSmithKline, Research Triangle Park, NC 27709. September 2003. FDA Rev date: n/aThis monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 10/14/2008
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