Digoxin immune fab

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Digoxin immune fab
Digibind.jpg
Bottle of digoxin immune fab
Clinical data
Trade names Digibind, others
AHFS/Drugs.com Consumer Drug Information
Routes of
administration
IV infusion, injection
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only) [1]
Pharmacokinetic data
Onset of action 30 min [2]
Elimination half-life 15 hours for DigiFab, 23 hours for Digibind
Duration of action 15 to 20 hrs [2]
Excretion Kidney
Identifiers
  • Anti-digoxin antibody fragment
DrugBank
ChemSpider
  • none
ChEMBL
Chemical and physical data
Formula C2085H3223N553O672S16
Molar mass 47301.88 g·mol−1
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Digoxin immune fab or digoxin-specific antibody is an antidote for overdose of digoxin. [3] It is made from immunoglobulin fragments from sheep that have already been immunized with a digoxin derivative, digoxindicarboxymethoxylamine (DDMA). Its brand names include Digibind (GlaxoSmithKline) and DigiFab (BTG plc).

Contents

Medical uses

It is used for digoxin toxicity. Digoxin toxicity can emerge during long-term therapy as well as after an overdose. It can occur even when the serum digoxin concentration is within the therapeutic range when one of the following is present: [4] [5]

  1. Hemodynamically unstable arrhythmia
  2. End organ damage
  3. digoxin level > 4 ng/ml if chronic ingestion
  4. digoxin level > 10 ng/ml if acute ingestion
  5. potassium > 5 mEq/L and symptomatic

Side effects of digoxin immune fab may occur:

Contraindications

Avoid use in hypokalemia as this drug, while reversing the effects of digitalis, will further reduce serum potassium levels and could precipitate dangerous and even fatal cardiac arrhythmias.

The patient must be closely monitored for anaphylactic shock, and anyone allergic to sheep protein, papain, bromelain, or papaya extracts (papain is used to cleave the antibody into Fab and Fc fragments) should not use ovine digoxin immune fab. Because it is relatively new, no drug interaction studies have been performed yet.[ citation needed ]

Pharmacology

It works by binding to the digoxin, rendering it unable to bind to its action sites on target cells. The complexes accumulate in the blood and are expelled by the kidney.

Regulatory information and clinical studies

Case series have reported benefits from anti‐digoxin Fab, but data regarding the response in acute or chronic poisoning are conflicting. Recent observational data support an effect in acute poisoning, but efficacy in chronic poisoning be minimally effective in alleviating cardiac toxicities in chronic digoxin poisoning. Data also support outcomes of acute digoxin poisoning without use of anti‐digoxin Fab. A case series of 147 patients showed that not all cases of acute digoxin overdose require anti‐digoxin Fab, nor should anti‐digoxin Fab dose be calculated based on ingested dose. In contrast, a higher mortality (7.6%) was noted in a case series of acute and chronic digoxin and digitoxin poisoning despite Fab being used first line. Further, a retrospective case‐controlled study of chronic digoxin poisoning did not observe a beneficial effect of anti‐digoxin Fab on mortality. An RCT (n = 66) in yellow oleander poisoning showed an early improvement in cardiac rhythm and hyperkalaemia from anti‐digoxin Fab, prompting early termination of the trial. It was not powered to detect a change in mortality and no deaths were noted. As with all foreign proteins, anaphylaxis, serum sickness or febrile reactions are a source of concern, especially with repeated administration. These reactions appear uncommon for example, in a study of 717 adults where only six patients (0.8%) exhibited any evidence of allergic response. Nevertheless, theoretically, patients previously dependent upon the inotropic effects of digoxin could develop heart failure and hypokalaemia could result within 1–5 hours, owing to intracellular shifts of potassium, as the effects of digoxin are reversed. Patients who require redigitalization must wait for the complexes to be eliminated from the body by the kidneys, this taking 2–3 days with normal renal function. Unfortunately, fab fragments interfere with both fluorescence excitation transfer immunoassays and radioimmunoassays for digoxin. This means that serum drug levels cannot be monitored until the drug-antibody complexes are cleared from the circulation. [6] [7]

Intellectual property

DigiFab is used as an antidote to treat a life-threatening overdose of digoxin or digitoxin.[ citation needed ] DigiFab is manufactured and distributed by BTG international Inc. under U.S. License No. 186. DigiFab is a sterile, lyophilized preparation of digoxin-immune ovine Fab (monovalent) immunoglobulin fragments. It 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. Each vial of DigiFab, 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 and is intended for intravenous administration.

Digibind is manufactured by GlaxoSmithkline, SpA, Parma Italy under US License No. 129. It’s distributed by GSK, Research Triangle park, NC 27709.

A patent to use digoxin immunoglobulins C07k16/44 as a regulator of the preeclamptic/eclamptic patient's sodium/potassium ATPase activity was approved in 2003 to Charles David Adair under application number WO2004011028A1.

Commercial aspects

Price increase was reported to range from US $380 to US $750 during 2013 for digoxin-Fab. However, these price increases are not reflective of the United States average AWP for digoxin-Fab as it represents Australian costs converted to US. Prior to 2011, Digibind and DigiFab pricing was US $797 per 38 mg vial and US $786 per 40 mg vial respectively. After GSK discontinued Digibind sale in USA in 2011, the AWP of DigiFab increases by 15% to US $903 per 40 mg vial. AWP of DigiFab has continued to increase as much as 54% occurring in March 2014 to US $2,370 per 40 mg vial. However, the cost may vary depending on wholesaler contractor manufacturer rebates.

Related Research Articles

<span class="mw-page-title-main">Cardiac glycoside</span> Class of organic compounds

Cardiac glycosides are a class of organic compounds that increase the output force of the heart and decrease its rate of contractions by inhibiting the cellular sodium-potassium ATPase pump. Their beneficial medical uses include treatments for congestive heart failure and cardiac arrhythmias; however, their relative toxicity prevents them from being widely used. Most commonly found as secondary metabolites in several plants such as foxglove plants and milkweed plants, these compounds nevertheless have a diverse range of biochemical effects regarding cardiac cell function and have also been suggested for use in cancer treatment.

<i>Digitalis</i> Genus of flowering plants in the family Plantaginaceae

Digitalis is a genus of about 20 species of herbaceous perennial plants, shrubs, and biennials, commonly called foxgloves.

Morvan's syndrome is a rare, life-threatening autoimmune disease named after the nineteenth century French physician Augustin Marie Morvan. "La chorée fibrillaire" was first coined by Morvan in 1890 when describing patients with multiple, irregular contractions of the long muscles, cramping, weakness, pruritus, hyperhidrosis, insomnia and delirium. It normally presents with a slow insidious onset over months to years. Approximately 90% of cases spontaneously go into remission, while the other 10% of cases lead to death.

<span class="mw-page-title-main">Digoxin</span> Plant-derived medication

Digoxin, sold under the brand name Lanoxin among others, is a medication used to treat various heart conditions. Most frequently it is used for atrial fibrillation, atrial flutter, and heart failure. Digoxin is one of the oldest medications used in the field of cardiology. It works by increasing myocardial contractility, increasing stroke volume and blood pressure, reducing heart rate, and somewhat extending the time frame of the contraction. Digoxin is taken by mouth or by injection into a vein. Digoxin has a half life of approximately 36 hours given at average doses in patients with normal renal function. It is excreted mostly unchanged in the urine.

<span class="mw-page-title-main">Digitoxin</span> Chemical compound

Digitoxin is a cardiac glycoside used for the treatment of heart failure and certain kinds of heart arrhythmia. It is a phytosteroid and is similar in structure and effects to digoxin, though the effects are longer-lasting. Unlike digoxin, which is eliminated from the body via the kidneys, it is eliminated via the liver, and so can be used in patients with poor or erratic kidney function. While several controlled trials have shown digoxin to be effective in a proportion of patients treated for heart failure, the evidence base for digitoxin is not as strong, although it is presumed to be similarly effective.

<span class="mw-page-title-main">Antivenom</span> Medical treatment for venomous bites and stings

Antivenom, also known as antivenin, venom antiserum, and antivenom immunoglobulin, is a specific treatment for envenomation. It is composed of antibodies and used to treat certain venomous bites and stings. Antivenoms are recommended only if there is significant toxicity or a high risk of toxicity. The specific antivenom needed depends on the species involved. It is given by injection.

<span class="mw-page-title-main">Hyperkalemia</span> Excess potassium in the blood

Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5 mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Occasionally when severe it can cause palpitations, muscle pain, muscle weakness, or numbness. Hyperkalemia can cause an abnormal heart rhythm which can result in cardiac arrest and death.

Polyclonal antibodies (pAbs) are antibodies that are secreted by different B cell lineages within the body. They are a collection of immunoglobulin molecules that react against a specific antigen, each identifying a different epitope.

<span class="mw-page-title-main">Cerberin</span> Chemical compound

Cerberin is a type of cardiac glycoside, found in the seeds of the dicotyledonous angiosperm genus Cerbera; including the suicide tree and the sea mango. As a cardiac glycoside, cerberin disrupts the function of the heart by blocking its sodium and potassium ATPase. Cerberin can be used as a treatment for heart failure and arrhythmia.

<span class="mw-page-title-main">Papain</span> Widely used enzyme extracted from papayas

Papain, also known as papaya proteinase I, is a cysteine protease enzyme present in papaya and mountain papaya. It is the namesake member of the papain-like protease family.

Crotalidae polyvalent immune Fab (ovine), sold under the brandname CroFab, is a snake antivenin, indicated for North American crotalid (rattlesnake, copperhead and cottonmouth/water moccasin) snake envenomation.

<span class="mw-page-title-main">Fragment antigen-binding region</span> Part of an antibody that binds to antigens

The fragment antigen-binding region is a region on an antibody that binds to antigens. It is composed of one constant and one variable domain of each of the heavy and the light chain. The variable domain contains the paratope, comprising a set of complementarity-determining regions, at the amino terminal end of the monomer. Each arm of the Y thus binds an epitope on the antigen.

<i>Cascabela thevetia</i> Species of plant

Cascabela thevetia is a poisonous plant native throughout Mexico and in Central America, and cultivated widely as an ornamental. It is a relative of Nerium oleander, giving it a common name yellow oleander.

<span class="mw-page-title-main">Oleandrin</span> Chemical compound

Oleandrin is a cardiac glycoside found in the poisonous plant oleander. As a main phytochemical of oleander, oleandrin is associated with the toxicity of oleander sap, and has similar properties to digoxin.

<span class="mw-page-title-main">Paracetamol poisoning</span> Toxicity due to paracetamol overdose

Paracetamol poisoning, also known as acetaminophen poisoning, is caused by excessive use of the medication paracetamol (acetaminophen). Most people have few or non-specific symptoms in the first 24 hours following overdose. These symptoms include feeling tired, abdominal pain, or nausea. This is typically followed by absence of symptoms for a couple of days, after which yellowish skin, blood clotting problems, and confusion occurs as a result of liver failure. Additional complications may include kidney failure, pancreatitis, low blood sugar, and lactic acidosis. If death does not occur, people tend to recover fully over a couple of weeks. Without treatment, death from toxicity occurs 4 to 18 days later.

<span class="mw-page-title-main">Tricyclic antidepressant overdose</span> Medical condition

Tricyclic antidepressant overdose is poisoning caused by excessive medication of the tricyclic antidepressant (TCA) type. Symptoms may include elevated body temperature, blurred vision, dilated pupils, sleepiness, confusion, seizures, rapid heart rate, and cardiac arrest. If symptoms have not occurred within six hours of exposure they are unlikely to occur.

<span class="mw-page-title-main">Digoxin toxicity</span> Medical condition

Digoxin toxicity, also known as digoxin poisoning, is a type of poisoning that occurs in people who take too much of the medication digoxin or eat plants such as foxglove that contain a similar substance. Symptoms are typically vague. They may include vomiting, loss of appetite, confusion, blurred vision, changes in color perception, and decreased energy. Potential complications include an irregular heartbeat, which can be either too fast or too slow.

<span class="mw-page-title-main">Salicylate poisoning</span> Medical condition

Salicylate poisoning, also known as aspirin poisoning, is the acute or chronic poisoning with a salicylate such as aspirin. The classic symptoms are ringing in the ears, nausea, abdominal pain, and a fast breathing rate. Early on, these may be subtle, while larger doses may result in fever. Complications can include swelling of the brain or lungs, seizures, low blood sugar, or cardiac arrest.

<span class="mw-page-title-main">Convallatoxin</span> Chemical compound

Convallatoxin is a glycoside extracted from Convallaria majalis.

References

  1. "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  2. 1 2 "digoxin immune Fab (ovine)". www.glowm.com. Retrieved 8 September 2020.
  3. DiDomenico RJ, Walton SM, Sanoski CA, Bauman JL (April 2000). "Analysis of the use of digoxin immune fab for the treatment of non-life-threatening digoxin toxicity". Journal of Cardiovascular Pharmacology and Therapeutics. 5 (2): 77–85. doi: 10.1053/XV.2000.5590 . PMID   11150387. S2CID   33064518.
  4. Nickson C (11 July 2014). "Digoxin Toxicity". LITFL • Life in the Fast Lane Medical Blog. Archived from the original on 20 February 2016. Retrieved 24 July 2017.
  5. "Digibind, DigiFab (digoxin immune FAB (Antidote)) dosing, indications, interactions, adverse effects, and more". Medscape. WebMD LLC. Retrieved 24 July 2017.
  6. Roberts DM, Gallapatthy G, Dunuwille A, Chan BS (March 2016). "Pharmacological treatment of cardiac glycoside poisoning". British Journal of Clinical Pharmacology. 81 (3): 488–495. doi:10.1111/bcp.12814. PMC   4767196 . PMID   26505271.
  7. Lip GY, Metcalfe MJ, Dunn FG (May 1993). "Diagnosis and treatment of digoxin toxicity". Postgraduate Medical Journal. 69 (811): 337–339. doi:10.1136/pgmj.69.811.337. PMC   2399830 . PMID   8346128.