1549 The adverse effects of dicobalt edetate are more severe in year-old child: case report and review of literature. Z Kardiol 2005; 94: References. 817-2 3. the absence of cyanide. Therefore, dicobalt edetate should I. Schaumann W, et a!. Kinetics of the Fab fragments of digoxin antibodies and of bound digoxin in patients with severe digoxin intoxication. Eur 1 not be given unless cyanide poisoning is confirmed and 30: Administration in renal impairment. In renal impairment, Clin Pharmacol 1986; 527-33. poisoning is severe such as when consciousness is impaired. 2. Ujhelyi MR, Robert S. Pharmacokinetic aspects of digoxin-specific Fab elimination of antibody-bound digoxin or digitoxin is therapy in the management of digitalis toxicity. Clin Pharmacokinet 1995; Oedema. A patient with cyanide toxicity developed delayed1·3 and antibody fragments can be detected in the 28: 483-93. plasma for 2 to 3 weeks after treatment.1 The rebound in 3. Renard C, et al. Pharmacokinetics of dig,'><i<1-sp,eei1ie Fab: effects of severe facial and pulmonary oedema after treatment with decreased renal function and age. 1997; 44: 135-8. dicobalt edetate.1 It has been suggested that when dicobalt free-digoxin concentrations that has been reported after edetate is used, facilities for intubation and resuscitation treatment with digoxin-specific antibody fragments (see P (Jrations should be immediately available. Poisoning, below), occurred much later in patients with r.�p renal impairment than in those with normal renal func­ Proprietary Preparations (details are given in Volume B) 1. Dodds C, McKnight C. Cyanide toxicity after immersion and the hazards tion. Those with severe renal impairment may need to be of dicobalt edetate. BMJ 1985; 291: 785-6. Single�ingredient Preparations. Austral.: Digibind; Canad.: observed for longer after treatment with antibody frag­ Digibindt; DigiFab; Fr.: Digibindt; Gr.: Digibind; DigiFab; Hong ments, and monitoring of free (unbound) plasma-digoxin Kong: Digitalis Antidote; UK: Digibind; DigiFab; USA: concentrations may be useful.1 Digibindt; DigiFab. Proprietary Preparations (details are given in Volume B) l. Flanagan RJ, Jones AL. Fab antibody fragments: some applications in clinical toxicology. 27: 1115-33. Single-ingredient Preparations. Fr.: Kelocyanor; 2. Al.len NM, et al. and pharmacokinetic profiles of digoxin Kelocyanor. immune Fab in four patients with renal impairment. DICP Ann Dimercaprol /BAN, riNN! Pharmacother 1991; 25: l315-20. 3. Ujhelyi MR, et al. Disposition of digoxin immune Fab in patients with BAL; f:lritis!1 Antl'LE;>y isite; Dirileitapro!um; Dim10rkaprol; kidney failure. Clin Pharmacal Ther 1993; 54: 388-94. Dimerk<jproH; Dimerkaproiis;).]I'IMepK<>nponc Digoxin-specific Antibody 23-Dimercaptopropan, 1-oi. Poisoning. Digoxin-specific antibody fragments can (\H50S2�124.2 Fragments reverse severe digitalis toxicity with an initial response · CA s � $:9-52-9. Digoxin tmmune F,ab (Ovine); .·· P(ab); Fragrr,entos usually seen within 30 minutes of the end of the infusion. licuerpos · · Fab Haemodynamic status normally improves, but in those ATC -'-- V03A B09. aQ e�p£:ch1cos . antidtgoxin�;. Fragmentos . antic\]e;rpos·antldigoxlna; .AHTV<AVI(OKG1H. with heart failure withdrawal of the inotropic support pro­ ATCVet."--- QV03A!309. UNi! ·.,-" OCPP32555X ATC-VOJABN vided by digoxin may produce a decline in cardiac func­ tion. Plasma potassium concentrations may fall rapidly Pharmacopoeias. In Chin., Bur. (see p. vii), Int., Jpn, US, and AtCV<?t � QV03AB24. after reversal of toxicity. Glycoside toxicity has been UNI/ Viet. �.YBI2NQZ IYN. reported to recur within 24 hours after treatment with Ph. Eur. 8; (Dimercaprol). A clear colourless or slightly antibody fragments. The reason for this is unclear, yellow liquid. Soluble in water and in arachis oil; miscible although it has been suggested that changes in the distri· Uses and Administration with alcohol and with benzyl benzoate. Store at 2 degrees to bution of glycoside and antibody fragments may play a Digoxin-specific antibody fragments are derived from 8 degrees in well-filled airtight containers. Protect from role.u It has been suggested that for either acute or antibodies produced in sheep immunised to digoxin. light. chronic toxicity, half the calculated loading dose (see Uses Digoxin has greater affinity for the antibodies than for and Administration, above) should be given initially, with USP 36; (Dimercaprol). A colourless or practically colourless tissue-binding sites, and the digoxin-antibody complex is further doses given only if response is inadequate or if liquid, having a disagreeable, mercaptan-like odour. Soluble then excreted in the urine. Digoxin-specific antibody toxicity recurs.3 Digoxin-specific antibody fragments are 1 in 20 of water; soluble in alcohol. in benzyl benzoate, and fragments are used to treat severe digoxin or digitoxin usually reserved for severe or life-threatening digitalis in methyl alcohol. Store at a temperature not exceeding 8 intoxication (p. 1355.1) in which conventional treatment is toxicity, such as that associated with significant hyperkal­ degrees in airtight containers. Protect from light. ineffective. Successful treatment of lanatoside C poisoning aemia, arrhythmias, or bradycardia;3 however they have has also been reported. also been used in patients with less severe toxicity but It is estimated that 38 or 40 mg (depending on the Uses and Administration vvith poor prognostic features such as underlying cardiac preparation) of antibody fragments can bind about Dimercaprol is a chelator that has been used in the disease or age over 55 years.4 500 micrograms of digoxin or digitoxin; the dose is thus treatment of acute poisoning by arsenic (p. 2449.1), gold Digoxin-specific antibody fragments have also been used calculated using the steady-state plasma concentration or (p. 131.3), and mercury (p. 2556.3). It may also be used in to reverse toxicity from cardiac glycosides present in other the amount of glycoside ingested. Doses are diluted in the treatment of poisoning by other heavy metals such as plants such as common or yellow oleander (p. 2574.3) and sodium chloride 0. 9% and given by intravenous infusion antimony and bismuth, and, with sodium calcium edetate, in poisoning due to preparations containing toad venom.5 over 30 minutes via a 0.22-micrometre in-line filter. If in acute lead poisoning (p. 2542.1). However, other I. Ujhelyi MR, Robert S. Pbarmacokinetk aspects of digoxin-specific Fab cardiac arrest is imminent the dose may be given as a bolus. chelators may be preferred for systemic use. Djmercaprol therapy in the management of digitalis toxicity. Clin Pharmacokinet 1995; In the case of incomplete reversal or recurrence of toxicity a 28: 483-93. has been used in refractory Wilson's disease (p. 1567.3). further dose can be given after several hours. 2. Flanagan RJ, Jones AL. Fab antibody fragments: some applications in Dimercaprol 5% has been applied as an ointment for skin After acute ingestion of an unknown amount of digoxin clinical toxicology. Drug Safety 2004; 27: 1115-3 3. lesions or as eye drops for ocular symptoms of arsenic 3. Bateman ON. Digoxin-specific antibody fragments: how much and or digitoxin a dose of 760 or 800 mg is suggested; toxicity. when? Toxicol Rev 2004; 23: 135-43. alternatively an initial dose of 380 or 400 mg can be given 4. Lapostolle F, et al. Digoxin-specific Fab fragments as single first-line The sulfhydryl groups on dimercaprol compete with with an additional 380 or 400 mg if required. For toxicity therapy in digitalis poisoning. Crit Care Med 2008; 36: 3014-18. endogenous sulfhydryl groups on proteins such as enzymes during chronic therapy when the steady-state plasma 5. Brubacher JR, et at. Treatment of toad venom poisoning with digoxin­ to combine with these metals; chelation by dimercaprol specific Fab fragments. Chest 1996; llO: 1282-8. concentration is unknown, a dose of 228 or 240 mg is therefore prevents or reverses any inhibition of the suggested. sulfhydryl enzymes by the metal and the dimercaprol-metal For doses in children, see Administration in Children, Adverse Effects and Precautions complex formed is readily excreted by the kidney. Since the below. complex may dissociate, particularly at acid pH, or be Allergic reactions to digoxin-specific antibody fragments Digoxin-specific antibody fragments are being investi­ oxidised, the aim of treatment is to provide an excess of have been reported rarely. A pruritic rash, facial flushing gated for the treatment of hypertension, particularly in dimercaprol in body fluids until the excretion of the metal is and swelling, and chills in the absence of fever have eclampsia and pre-eclampsia. complete. occurred on the day of treatment, and urticaria and Dimercaprol should be given by deep intramuscular thrombocytopenia have been reported up to 16 days after It has been suggested' that giving injection in the treatment of heavy metal poisoning. The Administration. treatment. digoxin-specific antibody fragments by infusion over 7 individual dose is determined by severity of symptoms and Patients known to be allergic to sheep protein and those hours, after an initial loading dose, could be useful in the causative agent. Single doses should not generally previously given digoxin-specific antibody fragments may ensuring adequate antibody concentrations are main­ exceed 3 mg/kg but single doses of up to 5 mg/kg may be be at greater risk of developing an allergic reaction. An tained to bind digoxin as it is released from tissue stores required initially in patients with severe acute poisoning. intradermal or skin scratch test may be used to test for over a prolonged period. Various dosage schedules are in use. sensitivity in those considered to be at high risk. In the UK, 400 to 800 mg is given on the first day of I. Schaumann W, ct al. Kinetics of the Fab fragmenb of digoxin antibodies Blood pressure, ECG, and potassium concentrations and of bound digoxin in patients wiTh severe digoxin intoxic<�tion.