ECG Patterns to Remember for Digoxin Toxicity

• First sign of digoxin toxicity in 10-15% of cases3

• Most common dysrhythmia related to digoxin toxicity4

• Bigeminy common4

Premature Ventricular Contractions

Premature Ventricular Contractions

SA Nodal Block (Type II)

SA Nodal Block (Type II)

Junctional Tachycardia

Junctional Tachycardia

Premature Atrial Contractions

Premature Atrial Contractions

Indicates life-threatening digoxin toxicity4,5

Almost any dysrhythmia or conduction abnormality may be seen with digoxin toxicity3,4,6

Digoxin toxicity should be considered with evidence of3:

• Increased automaticity

• Impaired conduction through the SA and AV nodes

Early Recognition of Digoxin Toxicity May Result in Improved Treatment Outcomes1,2

INDICATION DIGIFab is indicated for the treatment of known (or strongly suspected) life-threatening digoxin toxicity associated with ventricular arrhythmias or bradyarrhythmias unresponsive to atropine where measures beyond withdrawal of digoxin and correction of serum electrolyte abnormalities are considered necessary.

Please see Important Safety Information continued on next page and Summary of Product Characteristics.

Accelerated Junctional Rhythm

Accelerated Junctional Rhythm

Junctional RhythmsAV Junctional Escape Beats

AV Junctional Escape Beats

SA Nodal Block (Type I)

SA Nodal Block (Type I)

First Degree AV Block

First Degree AV Block

Non-paroxysmal Atrial Tachyardia with AV Block

Non-paroxysmal Atrial Tachycardia With AV Block

Ventricular Tachycardia

Ventricular Tachycardia

Ventricular Fibrilation

Ventricular Fibrillation

• Highly suggestive of life-threatening digoxin toxicity3,4Bidirectional Ventricular Tachycardia

Bidirectional Ventricular Tachycardia

• Highly suggestive of life-threatening digoxin toxicity4 Second Degree AV Block (Mobitz I)

Second Degree AV Block (Mobitz I)

• Early sign of digoxin toxicity4

• Progressive bradycardia can indicate life-threatening digoxin toxicity5

Sinus Bradycardia

Sinus Bradycardia

Third Degree AV Block

Third Degree AV Block

Enhancing the Effects of Digoxin Increases the Risk of Cardiac Dysrhythmias, Haemodynamic Instability, and Other Manifestations of Digoxin Toxicity2,7,8

CONTRAINDICATIONS

Hypersensitivity to the active substance or any of the excipients; sodium acetate, acetic acid, and mannitol.

SIDE EFFECTS, SPECIAL WARNINGS AND PRECAUTIONS FOR USE

UK National Poisons Information Service

It is advised to discuss management of patients with digoxin toxicity with the UK National Poisons Information Service at the following contact phone number: +44 344 892 0111.

Risk of infusion-related reactions or hypersensitivity

Infusion-related reactions or hypersensitivity reactions are possible. It is recommended that patients are monitored for signs and symptoms of anaphylaxis and an acute allergic reaction. Medical support must be readily available when DIGIFab is administered.

If an anaphylactic reaction occurs during an infusion, then stop administration immediately. Repeat dosing with DIGIFab may give rise to an anaphylactic reaction and must only be done when it is considered that the clinical benefit outweighs the risk.

The likelihood of an allergic reaction may be higher in subjects who:

• are allergic to sheep-derived proteins (as may be found in cheeses and meats). • are allergic to papain, an extract of the papaya fruit. Papain shares allergenic structures with (i) chymopapain and other papaya extracts, (ii) bromelain found in pineapple, (iii) dust mite allergens and (iv) latex allergens.

General management of patients

Patients should have continuous electrocardiographic monitoring during and for at least 24 hours after administration of DIGIFab. Temperature, blood pressure and potassium concentration should be monitored during and after DIGIFab administration. Patients

previously dependent on the inotropism of digoxin may develop signs of heart failure when treated with DIGIFab. After successful management of poisoning, digoxin has had to be reinstituted in some cases.

If, after several hours, toxicity has not adequately reversed or appears to recur, readministration of DIGIFab at a dose guided by clinical judgement may be required.

Failure of the patient to respond to DIGIFab should alert the physician to the possibility that the clinical problem may not be due to digoxin toxicity.

Immunoassay interference/Laboratory tests

Digoxin assay kits may not be able to measure accurately digoxin concentrations greater than 5 ng/mL (6.4 mmol/L). Exercise caution when using digoxin concentrations above these figures to calculate the dose.

DIGIFab may interfere with digoxin immunoassay measurements. Therefore, standard serum digoxin measurements may be clinically misleading until the Fab fragments are eliminated from the body. This may take several days or more than a week in patients with impaired renal function. The total serum digoxin concentration as measured by immunoassay may rise rapidly following administration of DIGIFab. Serum digoxin will be almost entirely bound by DIGIFab and therefore not able to react with receptors in the body.

DOSAGE AND METHOD OF USEThe recommended dose is dependent on whether the digoxin levels are known and can be found in the Summary of Product Characteristics. Reconstitute DIGIFab prior to administration and infuse intravenously over a 30-minute period.

For full information, please see Summary of Product Characteristics.

References: 1. Royal College of Emergency Medicine and National Poisons Information Service Guideline on Antidote Availability for Emergency Departments. January 2017. 2. Levine MD, O’Connor A. UpToDate. Updated January 2020. https://www.uptodate.com/contents/digitalis-cardiac-glycoside-poisoning. Accessed March 5, 2021. 3. Hack JB. In: Nelson LS et al, eds. Goldfrank’s Toxicologic Emergencies. McGraw-Hill Companies, Inc; 2011:936-945. 4. Goldberger AL et al. UpToDate. Updated January 2020. https://www.uptodate.com/contents/cardiac-arrhythmias-due-to-digoxin-toxicity. Accessed March 5, 2021. 5. DIGIFab Digoxin Immune Fab (ovine) [summary of product characteristics]. Protherics UK Limited; 2017. 6. Limon G et al. Turk J Emerg Med. 2016;16(1):17-21. 7. Digoxin Tablets BP [summary of product characteristics]. Accord-UK Ltd.; 2020. 8. Weil MH In: Pinsky MR, Payen D, eds. Update in Intensive Care and Emergency Medicine. Vol 42. Springer; 2005:9-17.

BTG and the BTG roundel are trademarks of BTG International Ltd.DIGIFab® is a registered trademark of BTG International Inc.© 2021 BTG International Inc. All rights reserved. UK-DGF-2100014 Mar 2021

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Early recognition and treatment can save lives1,2

Enhanced Contractility

• Ventricular tachydysrhythmias are more common in patients with chronic or late acute digoxin toxicity3

• Bradydysrhythmias in chronic or late acute digoxin toxicity occur by direct actions on the heart3

- Often minimally responsive to atropine, if at all

Impaired Conduction Through SA and AV Nodes

• Accentuation of vagal effects is more common in younger, healthy patients4

• Initial bradydysrhythmia in acute toxicity results from increases in vagal tone3

- Often responsive to atropine