Digoxin-specific antibody (Digoxin Immune Fab)

(di jox' in)

PCaution when used during lactation - Caution when used during pregnancy

LCaution when used during lactation - Caution when used during lactation

Molecule Info

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Indication(s) & Dosage

Digoxin Immune FAb (Ovine), is indicated for treatment of potentially life-threatening digoxin intoxication.3Although designed specifically to treat life-threatening digoxin overdose, it has also been used successfully to treat life-threatening digitoxin overdose.3Since human experience is limited and the consequences of repeated exposures are unknown, Digoxin Immune Fab is not indicated for milder cases of digitalis toxicity.

Manifestations of life-threatening toxicity include severeventricular arrhythmiassuch asventricular tachycardiaorventricular fibrillation, orprogressivebradyarrhythmias such as severesinus bradycardiaor second or third degreeheart blocknot responsive toatropine.

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-stateserumconcentrations greater than 10 ng/mL, often results incardiac arrest. Digitalis-induced progressive elevation of the serumpotassiumconcentration also suggests imminentcardiacarrest. If the potassium concentration exceeds 5 mEq/L in the setting of severe digitalis intoxication,therapywith Digoxin Immune Fab is indicated.

 

Dosage/Administration:

General Guidelines: The dosage of 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 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 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 Digoxin Immune Fab required to neutralize the known or estimated amount of digoxin or digitoxin in the body are given below.When determining the dose for 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 Digoxin Immune Fab at a dose guided by clinical judgment may be required.
  • Failure to respond to 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 Digoxin Immune Fab , the diagnosis of digitalis toxicity should be questioned.

Dosage Calculation: Digoxin Specific Antibody fragments (DigiFab) dose calculation.

Intravenous  Life-threatening digoxin intoxication  Adult: Each vial containing 38 mg of purified lyophilised digoxin-specific Fab fragments.  For acute ingestion of unknown amount: Usually, 20 vials is adequate to treat most life-threatening ingestions, may give as a single dose or give 10 vials, observe response, then give a second 10-vial dose if needed.  For acute ingestion of known amount: Based on number of tablets/capsules ingested, the number of vials needed can be calculated by taking the total amount of digoxin ingested divided by 0. 5.  Dose to be given via IV inj over 30 min; bolus inj may be used if cardiac arrest is imminent.  For more detailed information: Refer to full prescribing information.  Child: Each vial containing 38 mg of purified lyophilised digoxin-specific Fab fragments.  For acute ingestion of unknown amount: Usually, 20 vials is adequate to treat most life-threatening ingestions, may give as a single dose or give 10 vials, observe response, then give a second 10-vial dose if needed.  For acute ingestion of known amount: Based on number of tablets/capsules ingested, the number of vials needed can be calculated by taking the total amount of digoxin ingested divided by 0. 5.  Dose to be given via IV inj over 30 min; bolus inj may be used if cardiac arrest is imminent.  For more detailed information: Refer to full prescribing information. Reconstitution: Contents of each vial should be dissolved in 4 ml of sterile water for inj.  Reconstituted product should be used immediately; otherwise, it may be kept for up to 4 hr at 2-8°C.  Reconstituted product may be further diluted with sterile isotonic saline to a convenient volume.  Visually inspect solution for discolouration or particulate matter prior to admin.

Contraindications

Hypersensitivity to sheep products.

Special Precautions

Monitor serum potassium levels regularly especially during the 1st few hr of treatment.  BP and ECG should also be monitored regularly.  Caution when used in renal impairment as excretion of the complex may be reduced.  Pregnancy and lactation.  Infusion should be stopped and restarted at a slower rate if infusion-related reactions occur.

Adverse Drug Reaction(s)

May exacerbate heart failure, postural hypotension, hypokalaemia, phlebitis at site of inj.  Allergic reactions and serum sickness.

Lab Interference

May interfere with digitalis immunoassay measurements.

Pregnancy Category (FDA) and use in Specific Population

Use in Pregnancy: Category B2
There are no adequate and well-controlled studies using digoxin-specific antibody Fab fragments in pregnant women. Treatment of 5 pregnant baboons with digoxin-specific antibody Fab fragments by intravenous infusion daily (at up to 2-fold the maximum recommended human dose on a mg/kg basis) for 60 days during the third trimester resulted in no treatment-related adverse effects on tolerability, gestation, parturition or infant viability. Transient antibodies to digoxin-specific antibody Fab fragments were observed in 1 of 5
pregnant animals on Days 15 and 30 of the dosing period, but no later in gestation. No animal studies have evaluated the placental transfer of Digibind or its potential embryo-foetal effects when used in the first or second trimester.

In the absence of adequate experience of administration of digoxin-specific antibody Fab fragments to pregnant women, the potential benefit to the mother must be weighed against
the unknown risks to the foetus.

Use in lactation
It is not known whether Digibind is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Digibind is administered to a
nursing woman. Intravenous administration of Digibind to female baboons during gestation and early post natal period at doses of 18-27 mg/kg/day (up to approximately twice the clinical exposure at the MRHD, based on dose) was associated with infant serum Digibind levels up to 63% of maternal serum levels on post partum Day 7. It is not known whether the transfer of the Fab fragments occurred either in utero or during the lactation period.
No animal studies have been performed to determine the level of Digibind secreted in breast milk.

Paediatric use
Digibind has been successfully used in infants with no apparent adverse sequelae. As in all other circumstances, use of this drug in infants should be based on careful consideration of
the benefits of the drug balanced against the potential risk involved.

Carcinogenicity
There have been no studies performed in animals to evaluate carcinogenic potential.

Genotoxicity
There have been no studies performed to evaluate genotoxic potential.

Storage

Intravenous: Store at 2-8°C.

Pharmacology

After intravenous injection of Digoxin immune Fab (Ovine) in the baboon, digoxin specific Fab fragments are excreted in the urine with a biological half-life of about 9 to 13 hours. In humans with normal renal function the half-life appears to be 15 to 20 hours. Experimental
studies in animals indicate that these antibody fragments have a large volume of distribution in the extracellular space, unlike whole antibody which distributes in a space only about twice the plasma volume. Ordinarily, following administration of Digibind, improvement in signs and
symptoms of digitalis intoxication begins within one-half hour or less. The affinity of Digibind for digoxin is high and greater than that of digoxin for its receptor (sodium, potassium ATPase). The average affinity of Digibind for digitoxin is approximately 1.55 × 1010M-1.

Digibind binds molecules of digoxin, making them unavailable for binding at their site of action on cells in the body. The Fab fragment-digoxin complex accumulates in the blood, from which it is excreted by the kidney. The net effect is to shift the equilibrium away from binding of
digoxin to its receptors in the body, thereby reversing its effects.

Digoxin immune fab are specific antibodies used in the treatment of digitalis intoxication.  It binds with molecules of digoxin or digitoxin.  The digoxin-antibody complex is then excreted renally in the urine and removed from the body.  It is generally reserved for use in life-threatening digoxin or digitoxin intoxication cases whereby conventional treatment is ineffective.  Excretion: Half-life elimination: 15-20 hr; may be prolonged with renal impairment.  Excreted in the urine.

REFERENCE(S)

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.

Brand Manufacturer: GlaxoSmithKline (Digibind®).

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