Digoxin Immune Fab Ovine DB 00076 Approved Drug

Digoxin Immune Fab (Ovine) (DB 00076) Approved Drug Chemical Formula: C 2085 H 3223 N 553 O 672 S 16 Molecular Weight: 47301. 7 Digoxin Immune Fab is a sheep antibody (26 -10) FAB fragment from sheep immunized with the digoxin derivative Digoxindicarboxymethylamine. It is used as an antidote for overdose of digoxin. Indication/Usage For treatment of digitoxin overdose or digitalis glycoside toxicity. Pharmacodynamics Digi. Fab 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 Mechanism Of Action Binds excess digoxin or digitoxin molecules circulating in the blood. Half-Life 15 -20 hrs

Route of Elimination Cumulative urinary excretion of digoxin was comparable for both products and exceeded 40% of the administered dose by 24 hours. Volume of Distribution * 0. 3 L/kg [Digi. Fab]* 0. 4 L/kg [Digibind] Category Antidotes Affected Organisms Human and other Mammals Drug Interactions DB 08810 (Cinitapride): Cinitapride can alter the absorption of digoxin as it simulates gastric emptying. Sequence Heavy chain: EVQLQQSGPELVKPGASVRMSCKSSGYIFTDFYMNWVRQSHGKSLDYIGYISPYSGVTGYNQKFKGKATLTVDKSSST AYMELRSLTSEDSAVYYCAGSSGNKWAMDYWGHGASVTVSSAKTTAPSVYPLAPVCGDTTGSSVTLGCLVKGYFPEP VTLTWNSGSLSSGVHTFPAVLQSDLYTLSSSVTVTSSTWPSQSITCNVAHPASSTKVDKKIEP Light chain: DVVMTQTPLSLPVSLGDQASISCRSSQSLVHSNGNTYLNWYLQKAGQSPKLLIYKVSNRFSGVPDRFSGSGSGTDFTLK ISRVEAEDLGIYFCSQTTHVPPTFGGGTKLEIKRADAAPTVSIFPPSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSER QNGVLNSWTDQDSKDSTYSMSSTLTLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC Experimental Properties Melting Point- 61 °C for FAB Fragment; 71 °C for whole m. Ab Hydrophobicity: 0. 343 Isoelectric Point: 8. 01

Brands Digibind - Galaxo Smith Kline Digi. Fab - Protherics Inc Digibind DIGIBIND, Digoxin Immune Fab (Ovine), is a sterile lyophilized powder of antigen binding fragments (Fab) derived from specific antidigoxin antibodies raised in sheep. Production of antibodies specific for digoxin involves conjugation of digoxin as a hapten to human albumin. Sheep are immunized with this material to produce antibodies specific for the antigenic determinants of the digoxin molecule. The antibody is then papain-digested and digoxin-specific Fab fragments of the antibody are isolated and purified by affinity chromatography. These antibody fragments have a molecular weight of approximately 46, 200. DIGIBIND, Digoxin Immune Fab (Ovine), is a sterile lyophilized powder of antigen binding fragments (Fab) derived from specific antidigoxin antibodies raised in sheep. It is administered as a intravenous injection after reconstitution with Sterile Water for Injection. Formulation Each vial, which will bind approximately 0. 5 mg of digoxin (or digitoxin), contains 38 mg of digoxinspecific Fab fragments derived from sheep plus 75 mg of sorbitol as a stabilizer and 28 mg of sodium chloride. The vial contains no preservatives. Used/Prescribed for DIGIBIND, Digoxin Immune Fab (Ovine), is indicated for treatment of potentially life-threatening digoxin intoxication. Although designed specifically to treat life-threatening digoxin overdose, it has also been used successfully to treat life-threatening digitoxin overdose. Since human experience is limited and the consequences of repeated exposures are unknown, DIGIBIND is not indicated for milder cases of digitalis toxicity.

Dosage 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). Dose (in # of vials) = Total digitalis body load in mg / 0. 5 mg of digitalis bound/vial. Contraindications There are no known contraindications to the use of DIGIBIND. Side- effects Allergic reactions to DIGIBIND (digoxin immune fab) have been reported rarely. Patients with a history of allergy, especially to antibiotics, appear to be at particular risk. In a few instances, low cardiac output states and congestive heart failure could have been exacerbated by withdrawal of the inotropic effects of digitalis. Hypokalemia may occur from re-activation of (sodium, potassium) ATPase. Patients with atrial fibrillation may develop a rapid ventricular response from withdrawal of the effects of digitalis on the atrioventricular node. Drug Interactions No information provided References 1. Wenger TL, Butler VP Jr, Haber E, Smith TW. Treatment of 63 severely digitalis-toxic patients with 2. 3. digoxin-specific antibody fragments. J Am Coll Cardiol. 1985; 5: 118 A-123 A http: //www. rxlist. com/digibind-drug. htm http: //dailymed. nlm. nih. gov/dailymed/archives/fda. Drug. Info. cfm? archiveid=12121

Digi. Fab These fragments are obtained from the blood of healthy sheep immunized with a digoxin derivative, digoxin-dicarboxymethoxylamine (DDMA), a digoxin analogue which contains the functionally essential cyclopentaperhydrophenanthrene: lactone ring moiety coupled to keyhole limpet hemocyanin (KLH). The final product is prepared by isolating the immunoglobulin fraction of the ovine serum, digesting it with papain and isolating the digoxin-specific Fab fragments by affinity chromatography. These antibody fragments have a molecular weight of approximately 46, 000 Da. Digi. Fab® [Digoxin Immune Fab (Ovine)] is a sterile, purified, lyophilized preparation of digoxin-immune ovine Fab (monovalent) immunoglobulin fragments which are administered intravenously Formulation Each vial of Digi. Fab, which will bind approximately 0. 5 mg digoxin, contains 40 mg of digoxin immune Fab, 75 mg (approx) of mannitol USP, and 2 mg (approx) sodium acetate USP as a buffering agent. The product contains no preservatives after reconstitution with 4 m. L of Sterile Water for Injection USP. Used/Prescribed for Digi. Fab is indicated for the treatment of patients with life-threatening or potentially life-threatening digoxin toxicity or overdose. Although designed specifically to treat digoxin overdose, a product very similar to Digi. Fab (Digibind) has been used successfully to treat life-threatening digitoxin overdose. Dosage For adult patients who are in acute distress or for whom a serum digoxin concentration is not available, 6 vials (240 mg) should be adequate to reverse most cases of toxicity. . Contraindications There are no known contraindications to the use of Digi. Fab

Side- effects Exacerbation of low cardiac output states and congestive heart failure due to the withdrawal of inotropic effect of digitalis. Hypokalemia due to reactivation of the sodium-potassium ATPase. Rapid ventricular response in patients with atrial fibrillation due to withdrawal of the effects of digitalis on the atrioventricular node. Rare allergic reactions Patients with a history of allergy, especially to antibiotics, appear to be at particular risk. Drug Interactions No information provided References 1. http: //dailymed. nlm. nih. gov/dailymed/drug. Info. cfm? setid=6832767 f-db 6 b-4 eea-b 88 bbdfc 905749 e 1