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Digoxin Toxicity. Allison A. Muller, PharmD, D.ABAT Dr. Muller reports a financial relationship with BTG International, Inc. as a consultant.  This slide presentation was produced as part of this relationship. She reports no other conflicts. The supervising editor was Richard C. Dart, MD, PhD.

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slide1

Digoxin Toxicity

Allison A. Muller, PharmD, D.ABAT

Dr. Muller reports a financial relationship with BTG International, Inc. as a consultant.  This slide presentation was produced as part of this relationship. She reports no other conflicts. The supervising editor was Richard C. Dart, MD, PhD.

cardioactive steroids
Cardioactive Steroids
  • Cardioactive Steroids (CAS), orcardiac glycosides, developed their name from the strong cardiac effect on the heart and the recognition of a common steroid nucleus at the heart of these drugs.
  • The most common pharmaceutical product is digoxin. Other preparations available internationally include digitoxin, ouabain, lanatoside C, deslanoside, and gitaline.
  • There is evidence in the Ebers Papyrus (Papyrus Smith) that the Egyptians used plants containing CAS at least 3000 years ago.

2

cardioactive steroids sources
Cardioactive Steroids: Sources

Many plants contain cardioactive steroids

  • Digitalis purpurea (foxglove), Nerium oleander (oleander), Convallaria majalis (lily of the valley), Drimia maritima (red squill)
  • Toxicity may result from use of herbal products or teas derived from such plants or direct ingestion of the plant itself

Bufo marinus toad – dried secretions are a supposed aphrodisiac and contain a cardioactive steroid

Giardina EG, Sylvia L. Up to Date, Rose BD (ED), Waltham, MA, 2012.

3

cardioactive steroids effect
Cardioactive Steroids: Effect
  • At therapeutic serum concentrations, CAS increase automaticity and shorten the repolarization intervals of the atria and ventricles.
  • Changes in nodal conduction cause a decrease in ventricular response rate to suprajunctional rhythms and by PR interval prolongation (digitalis effect).

4

digoxin mechanism
Digoxin: Mechanism

Formulations

Injection (IV; rarely used IM)

Oral Solution

Tablets

Mechanism of Action

Inhibit active transport of Na+ and K+ across the cell membrane during repolarization by binding to a specific site on the extracellular face of the alpha-subunit of the membrane Na+-K+-ATPase

Digoxin

K+

K+

K+

K+

Ca++

Ca++

Ca++

Na+

K+

K+

Na+

K+

Ca++

Na+

Na+

Na+

K+

Na+

Na+

K+

Ca++

Na+

Ca++

K+

Na+

Na+

Na+

Na+

Arispe N, Diaz JC, Simakova O, Pollard HB. Heart failure drug digoxin induces calcium uptake into cells by forming transmembrane calcium channels. Proc Natl Acad Sci. 2008;105:2610-2615.

Middlekauff HR. Int Med 1998; 37: 112-122.

5

digoxin therapeutic role
Digoxin: Therapeutic Role

Disease states used in:

  • Atrial fibrillation:
  • Control of ventricular response rate in patients with chronic atrial fibrillation
  • Heart failure:
  • Increases left ventricular ejection fraction by increasing exercise capacity, and decreasing heart failure-related hospitalizations and emergency room visits. Likely no effect on mortality

Used in adults and pediatrics

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/009330s026lbl.pdf, FDA Package Insert for Digoxin, accessed 11/13/2013

6

digoxin kinetics
Digoxin: Kinetics

Volume of Distribution

Protein Binding

Half Life

Time to peak (serum)

5-7 L/kg

  • 25%

Age, Renal, and cardiac function dependent

Approximately 38 Hours (parent drug)

Oral: 1-3 hours

Distribution phase: 6-8 hours

Steady state: 7-10 Days

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/009330s026lbl.pdf, FDA Package Insert for Digoxin, accessed 11/13/2013

7

digoxin times to onset of pharmacologic effect and to peak effect of preparations
Digoxin: Times to Onset of Pharmacologic Effect and to Peak Effect of Preparations

Tablets

IV/Injection

Time to onset of Effect: 0.5-2 Hours

Time to Peak Effect: 2-6 Hours

Time to onset of Effect: 5-30 Minutes

Time to Peak Effect: 1-4 Hours

8

digoxin toxicity
Digoxin Toxicity

Overall use of digoxin has declined approximately 10% in hospitalized acute decompensated heart failure patients.

(from 31.4% in 2001 to 23.5% in 2004)

Number of patients with admitted digoxin poisoning has remained stable (approximately 1,500/year)

Use of digoxin-specific antibody fragments has increased (approximately 20%)

In 2011, there were 2,513 cases involving cardiac glycosides reported to U.S. poison control centers. Of these, 90 experienced major effects (i.e, life threatening resulting in prolonged hospitalization) and 26 died.

Hussain Z, Swindle J, Hauptman PJ. J Card Fail 2006; 12: 343.

Bronstein AC, Spyker DA, Cantilena LR, et al. Clin Tox 2012; 50:911-1164

9

risk factors for digoxin toxicity
Risk Factors for Digoxin Toxicity

Kidney Injury: digoxin is primarily eliminated by the kidneys

Age: elderly are more likely to have decreased renal function and taking potentially interacting concomitant medications

Electrolyte Imbalance: increases sensitivity to digoxin effects

Fluid Status: fluid loss or poor fluid intake can lead to electrolyte imbalances

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/009330s026lbl.pdf, FDA Package Insert for Digoxin, accessed 11/13/2013

10

digoxin causes of toxicity
Digoxin: Causes of Toxicity

Hypokalemia

Hypercalcemia

Hypomagnesemia

  • Results in increased digoxin binding increasing its therapeutic and toxic effects.
  • Digoxin enhances Ca+2 absorption into cardiac myocytes, which is one of the ways it increases inotrophy. This can also lead to Ca+2 overload and increased susceptibility to digitalis-induced arrhythmias.
  • Can sensitize the heart to digitalis-induced arrhythmias (includes any arrhythmia except supraventricular tachydysrhythmias).

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/009330s026lbl.pdf, FDA Package Insert for Digoxin, accessed 11/13/2013

11

digoxin causes of toxicity1
Digoxin: Causes of Toxicity

Drug interactions: many commonly used drugs interact with digoxin

  • No P450 Interactions
  • Drugs that alter renal clearance can affect digoxin concentration

Gomes T , Mamdani MM, Juurlink DN. Clin Pharm & Therap 2009; 86: 383-386.

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/009330s026lbl.pdf, FDA Package Insert for Digoxin, accessed 11/13/2013

12

digoxin causes of toxicity2
Digoxin: Causes of Toxicity

Drug interactions: many commonly used drugs interact with digoxin

  • Loop and Thiazide Diuretics decrease serum potassium levels:
    • furosemide
    • hydrochlorthiazide

Gomes T , Mamdani MM, Juurlink DN. Clin Pharm & Therap 2009; 86: 383-386.

13

digoxin causes of toxicity3
Digoxin: Causes of Toxicity

Drug interactions: many commonly used drugs interact with digoxin

  • Various drugs alter the mechanism of digoxin renal excretion or intestinal p-glycoprotein activity
      • verapamil
      • diltiazem
      • quinidine
      • amiodarone

Gomes T , Mamdani MM, Juurlink DN. Clin Pharm & Therap 2009; 86: 383-386.

http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/009330s026lbl.pdf, FDA Package Insert for Digoxin, accessed 11/13/2013

14

digoxin causes of toxicity4
Digoxin: Causes of Toxicity

Increased Serum Levels

  • Amiodarone
  • Benzodiazepines
  • Bepridil
  • Cyclosporine
  • Diphenoxylate
  • Indomethacin
  • Itraconazole
  • Macrolide Antibiotics
  • Propafenone
  • Propantheline
  • Quinidine
  • Quinine
  • Spironolactone
  • Tetracyclines
  • Verapamil
  • Decreased Serum Levels
  • Oral aminglycosides
  • Al+/Mg+ containing antacids
  • Antineoplastics
  • Activated charcoal
  • Cholestyramine
  • Colestipol
  • Kaoline / pectin
  • Metoclopramide
  • Neomycin
  • Penicillamine
  • Rifampin
  • St. John’s wort
  • Sulfasalazine

.

Gomes T , Mamdani MM, Juurlink DN. Clin Pharm & Therap 2009; 86: 383-386.

15

digoxin causes of toxicity con t
Digoxin: Causes of Toxicity, Con’t

Enhanced Pharmacodynamic Effects

  • Beta-blockers
  • Calcium
  • Verapamil
  • Diltiazem
  • Succinylcholine
  • Sympathomimetics
  • Diuretics

Antagonize Pharmacodynamic Effects

  • Thyroid hormones

Gomes T , Mamdani MM, Juurlink DN. Clin Pharm & Therap 2009; 86: 383-386.

16

digoxin toxicity1
Digoxin: Toxicity

Signs/symptoms of acute toxicity

Gastrointestinal

Neurological

nausea, vomiting, abdominal pain

weakness, confusion

Electrolyte

Cardiac

Hyperkalemia (> 5.5 mEq/L is a poor prognostic sign)

bradycardia, heart block, several types of arrhythmias

Schaeffer TH, Mlynarchek SL, Stanford CF. JAOA 2010; 110: 587-592

17

digoxin toxicity2
Digoxin: Toxicity

Signs/symptoms of chronic toxicity

Gastrointestinal

Neurological

Patients may have more subtle signs of acute digoxin toxicity (nausea, anorexia)

confusion, drowsiness, headache, hallucinations

Visual

sensitivity to light, yellow halos around lights, blurred vision

Schaeffer TH, Mlynarchek SL, Stanford CF. JAOA 2010; 110: 587-592

18

digoxin laboratory analyses
Digoxin: Laboratory Analyses

Interpreting laboratory values in the digoxin poisoned patient

Hyperkalemia: > 5.5 mEq/L in the acutely poisoned digoxin patient (100% Mortality)

Poor prognostic sign in acute toxicity. Antidote warranted when > 5 mEq/L due to 50% mortality for potassium 5 mEq/L – 5.5 mEq/L

Hypokalemia: Can predispose the patient to further dysrhythmias and should be corrected with close monitoring to avoid hyperkalemia. Goal Potassium level 4.0 mEq/L - 5.0 mEq/L

19

digoxin laboratory analyses1
Digoxin: Laboratory Analyses

Interpreting laboratory values in the digoxin poisoned patient

Hypomagnesemia may cause refractory hypokalemia

Administration of magnesium is contraindicated in:

Bradycardia

Heart block

  • Pre-existing hypermagnesemia
  • Decreased renal function or failure

20

digoxin laboratory analyses2
Digoxin: Laboratory Analyses

Digoxin levels in the poisoned patient

  • Obtaining an immediate digoxin level in an acutely poisoned patient will not reflect the peak serum level as the distribution phase of digoxin is long. An initial 4-6 hour post-ingestion level is appropriate.
  • Useful following administration of digoxin-specific Fab fragments

Unbound digoxin

  • Serum concentrations predict cardiac concentrations
  • Fab fragments of digoxin-specific antibodies will cause a rise in total digoxin levels (as Fab bound digoxin is also being measured)

Total digoxin

(bound & unbound)

21

diagnosis of digoxin toxicity
Diagnosis of Digoxin Toxicity

What is needed?

History

Signs and symptoms

EKG

Digoxin levels

Electrolytes

22

diagnosis of digoxin toxicity1
Diagnosis of Digoxin Toxicity

What is needed?

History

Risk factors for digoxin toxicity including age of patient (for patients chronically using digoxin therapeutically)

Initiation or discontinuation of drugs that potentially interact with digoxin

Any disease changes (such as thyroid disease)

Altered renal function

23

diagnosis of digoxin toxicity2
Diagnosis of Digoxin Toxicity

What is needed?

Signs and Symptoms

Acute overdose:

Gastrointestinal: nausea, vomiting

Central Nervous System:

confusion, weakness, lethargy

Electrolyte changes: hyperkalemia

Cardiac Signs: sinus bradycardia, second or third degree AV block. Any type of dysrhythmia is possible

24

diagnosis of digoxin toxicity3
Diagnosis of Digoxin Toxicity

What is needed?

Signs and Symptoms

Chronic overdose (symptoms usually insidious in onset):

Gastrointestinal:

anorexia, nausea,

vomiting, weight loss

Central Nervous System:delirium, hallucinations, confusion,, lethargy (seizures are possible but rare)

Visual:photophobia, changes in color vision (such as yellow halos around lights)

  • Electrolyte changes:hyperkalemia (sometimes hypokalemia especially if diuretics are used)

Cardiac Signs:bradydysrhythmias (often unresponsive to atropine) ventricular tachydysrhythmias

25

diagnosis of digoxin toxicity4
Diagnosis of Digoxin Toxicity

What is needed?

EKG

Almost any arrhythmia or conduction abnormality may be seen with digitalis toxicity.

26

diagnosis of digoxin toxicity5
Diagnosis of Digoxin Toxicity

What is needed?

Digoxin levels

Therapeutic range of digoxin has historically been 0.5 - 2.0 ng/mL.

Current FDA Package Insert recommends 0.5 - 1.0 ng/mL.

Toxicity begins >2.0 ng/mL

  • However, this can be misleading in the acutely poisoned patient
    • Stat levels may not correlate with the severity of the poisoning especially in acute ingestions
    • Digoxin’s long distribution phase results in high serum levels for 6-12 hours prior to completed tissue distribution

27

diagnosis of digoxin toxicity6
Diagnosis of Digoxin Toxicity

What is needed?

Electrolytes

Hypokalemia results in increased digoxin binding increasing its therapeutic and toxic effects.

Hypercalcemia enhances digitalis-induced inotropy leading to possible Ca+2 overload and increased susceptibility to digitalis-induced arrhythmias.

Hypomagnesemia can sensitize the heart to digitalis-induced arrhythmias.

28

digoxin toxicity available treatments
Digoxin Toxicity: Available Treatments

Decontamination/enhanced elimination

For acute overdose: Activated charcoal can adsorb digoxin in the gut

Enhanced elimination (dialysis, hemoperfusion) does not effectively remove digoxin due to large volume of distribution and relatively high protein binding

29

digoxin toxicity available treatments1
Digoxin Toxicity: Available Treatments

Fab fragments of digoxin-specific antibodies

Available U.S. products:

  • DigiFab® digoxin immune fab (ovine) BTG International, Inc.

30

digoxin immune fab ovine indications
Digoxin immune fab (ovine): Indications

Life-threatening or potentially life-threatening digoxin toxicity or overdose, which includes:

  • Known suicidal or accidental Ingestion of fatal digoxin doses:
  • 10 mg or more in healthy adults
  • 4 mg (0.1 mg/kg) or more in healthy children
  • An amount that results in steady state digoxin
  • concentrations of > 10 ng/mL
  • Chronic ingestions:
  • Serum digoxin > 6 ng/mL in adults or 4 ng/mL in children

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

31

digoxin immune fab ovine indications1
Digoxin immune fab (ovine): Indications

Life-threatening or potentially life-threatening digoxin toxicity or overdose, which includes:

  • Severe ventricular arrhythmias
  • Progressive bradycardia
  • Second or third degree heart block unresponsive to atropine
  • Serum potassium levels > 5.5 mEq/L (adults) or 6 mEq/L (children) with rapidly progressive signs and symptoms of digoxin toxicity

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

32

digoxin immune fab ovine mechanism of action
Digoxin immune fab (ovine): Mechanism of Action

Binds to digoxin molecules, reducing free digoxin levels

  • Results in a shift in the equilibrium away from receptor binding

Fab-digoxin complexes are cleared by the kidney and mononuclear phagocyte system

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

33

digoxin immune fab ovine dosing
Digoxin immune fab (ovine): Dosing

Acute ingestion: unknown amounts of digoxin and unknown serum concentration

  • 20 vials of Digoxin immune fab (ovine)
  • Monitor for volume overload in children < 20 kg
  • Can split dose into 10 vials followed by another 10 vials to avoid a febrile reaction

DigiFab® Prescribing Information, ,an 2012, BTG International, Inc.

34

digoxin immune fab ovine dosing1
Digoxin immune fab (ovine): Dosing

Acute ingestion: known amounts of digoxin

Amount of digoxin ingested (mg)*

Dose In Vials =

0.5 mg/Vial

* multiply mg by bioavailability of the tablet formulation:

0.25 mg tabs (80% bioavailability)

0.2 mg tabs (100% bioavailability)

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

35

digoxin immune fab ovine dosing2
Digoxin immune fab (ovine): Dosing

Chronic ingestion: unknown serum digoxin concentration

6 Vials of Digoxin immune fab (ovine) in Adults and Children >20 Kg

1 Vial of Digoxin immune fab (ovine) in Infants and Children < 20 Kg

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

36

digoxin immune fab ovine dosing3
Digoxin immune fab (ovine): Dosing

Chronic ingestion: known digoxin serum concentration

(Serum Digoxin ng/mL) x (Weight in kg)

Dose In Vials =

100

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

37

digoxin immune fab ovine preparation
Digoxin immune fab (ovine): Preparation
  • One vial contains 40 mg of digoxin immune fab protein
    • Contains no preservatives and is for one-time use only

Reconstitution: add 4 mL Sterile Water for Injection (10 mg/mL solution of digoxin immune fab protein) and gently mix

Use immediately or store in refrigerator for up to 4 hours (do not freeze)

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

38

digoxin immune fab ovine preparation1
Digoxin immune fab (ovine): Preparation

Add reconstituted product to appropriate 0.9% sodium chloride for injection

  • For infants and very small children
    • use undiluted reconstituted solution using tuberculin syringe
    • reconstituted vial can also be diluted with an additional 36 mL of isotonic saline for 1mg/mL concentration

Visual inspection

Do not use if solution is cloudy, turbid or contains particulates

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

39

digoxin immune fab ovine administration
Digoxin immune fab (ovine): Administration

30 minute slow IV infusion

Can be given by IV bolus injection if cardiac arrest is imminent

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

40

digoxin immune fab ovine dosing administration
Digoxin immune fab (ovine): Dosing/administration

If toxicity is not adequately reversed or recurs, measure free (not total) serum digoxin concentrations

Repeat doses may be guided by clinical judgment

If digoxin toxicity is not at all reversed, consider another diagnosis

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

41

digoxin immune fab ovine use in special populations
Digoxin immune fab (ovine): Use in Special Populations

Pregnancy category C

Nursing mothers

Unknown if may cause fetal harm. Should be given to pregnant patient only if clinically indicated

Unknown if excreted in breast milk

Pediatric use

Geriatric patients

Pediatric safety data are limited. Pediatric dosing estimations are based on adult dosing

Renal function needs to be monitored closely for recurrent toxicity

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

42

digoxin immune fab ovine warnings
Digoxin immune fab (ovine): Warnings

Monitor potassium level frequently as a rapid drop in serum potassium may occur following digoxin immune fab (ovine): administration

DigiFab® Prescribing Information, ,Jan 2012, BTG International, Inc.

43

digoxin immune fab ovine warnings1
Digoxin immune fab (ovine): Warnings

Patients who require digoxin’s inotropic action may deteriorate secondary to the withdrawal of digoxin’s inotropic action by digoxin immune fab (ovine)

Additional inotropic support may be required for these patients (e.g, dopamine, dobutamine or vasodilators)

Re-digitalization may need to be postponed until digoxin immune fab (ovine) has cleared (several days to more than a week of impaired renal function)

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

44

digoxin immune fab ovine warnings2
Digoxin immune fab (ovine): Warnings

Do not administer digoxin immune fab (ovine) to papaya-or papain-hypersensitive patients unless the benefits clearly outweigh the risks

Patients with allergies to sheep protein or prior treatment with ovine antibodies or Fab are at risk for an anaphylactic reaction

Standard emergency care and termination of digoxin immune fab (ovine) are warranted for patients with anaphylaxis/ hypersensitivity reactions

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

45

digoxin immune fab ovine adverse effects most common
Digoxin immune fab (ovine): Adverse effects (most common)

Worsening of congestive heart failure 13%

Hypokalemia 13%

A rapid shift of potassium back into the cell can occur when digoxin toxicity is reversed by digoxin immune fab (ovine)

Serum potassium should be followed closely and supplementation should be given cautiously

Worsening atrial fibrillation 7%

DigiFab® Prescribing Information, Jan 2012, BTG International, Inc.

46

digoxin immune fab ovine
Digoxin immune fab (ovine):

Minimum stocking recommendation: 15 vials (for approximately 8 hours of initial therapy)

Emergency department stocking: for availability within one hour

Dart RC, Borron SW, Caravati EM, et al. Ann Emer Med 2009; 54: 386-394.

47

resources
Resources

Website for product information

US Poison Centers

(calls routed to appropriate center)

www.digifab.us

800-222-1222

BTG Medical Info/Adverse Event Reporting

Customer Service including availability

877-377-3784

877-852-8542

48

digoxin toxicity case 1
Digoxin Toxicity: Case 1

76 year old woman with history of atrial fibrillation, hypertension, renal impairment, breast cancer, osteoarthritis. Stroke 1 month prior to admission.

Medications: digoxin 250 mcg once daily, amlodipine, lisinopril, indapamide SR, simvastatin, clopidogrel, bisoprolol, omeprazole, erythromycin

Presents with nausea, vomiting, change in vision, lethargy

VS: BP “normal”; HR 35-38 bpm

Labs

Digoxin levels: prior to admission: 3.4 ng/mL (0.8-2 ng/mL normal range for this lab)

On admission: 2.9 ng/mL

Increased digoxin dose from 125 mcg/day to 250 mcg/day 28 days ago

Kolev KK. Digoxin – a friend or foe. BMJ Case Reports 2012 Sept 24

49

digoxin toxicity case 11
Digoxin Toxicity: Case 1

Summary: elderly patient with renal impairment, signs/symptoms of (chronic) digoxin poisoning with elevated digoxin level

Potential drug interactions:

Amlodipine

Bisoprolol

Erythromycin

  • (Ca+2channel blocker) can increase digoxin level and enhance digoxin AV blocking effect
  • (ßblocker) can enhance digoxin’s bradycardic effect
  • (macrolide antibiotic) can increase digoxin level

Kolev KK. Digoxin – a friend or foe. BMJ Case Reports 2012 Sept 24Gomes T, Mamdani MM, Juurlink DN. Clin Pharmacol & Therap 2009; 86: 383-386.

50

digoxin toxicity case 12
Digoxin Toxicity: Case 1

Received digoxin-specific antibody fragments (Fab)

Weight 108 kg

Digoxin level: 2.9 ng/mL

(Serum Digoxin ng/mL) x (Weight in kg)

Fab Dose In Vials =

100

3 vials administered

Kolev KK. Digoxin – a friend or foe. BMJ Case Reports 2012 Sept 24

51

digoxin toxicity case 13
Digoxin Toxicity: Case 1

6 hours post digoxin Fab infusion: digoxin 1.9 ng/mL

At discharge (91 hours post digoxin Fab infusion): digoxin 1 ng/mL, HR 65 bpm, digoxin toxicity signs/symptoms resolved

Monitoring

HR: improved (35-38 bpm to 65 bpm at discharge)

BP: remained stable

EKG: unchanged from baseline (atrial fibrillation)

K+not provided in this report (although this was a chronic toxicity not acute)

Kolev KK. Digoxin – a friend or foe. BMJ Case Reports 2012 Sept 24

52

digoxin toxicity case 14
Digoxin Toxicity: Case 1

Approaches to digoxin poisoning in the chronically poisoned patient will depend on the status of the patient (signs/symptoms, age, renal function, cardiac status)

This was an elderly patient with impaired renal function who clearly had digoxin toxicity and an elevated level.

The clinical decision was made to treat promptly with digoxin Fab rather than prolong her clinical course.

Kolev KK. Digoxin – a friend or foe. BMJ Case Reports 2012 Sept 24

53

supplemental slides
Supplemental slides

(includes off-label information)

54

treating non pharmaceutical sources of cardioactive steroids
Treating non-pharmaceutical sources of cardioactive steroids

Natural cardioactive steroid sources:

Yellow oleander

Oleander

Squill

Lily of the valley

Bufos marinus toad

DigiFab®is not FDA-approved for treating poisoning from these naturally occurring steroids; however, there is evidence in the literature for its use.

Howland MA. Antidotes in Depth: Digoxin-Specific Antibody Fragments. Goldfrank’s Toxicologic Emergencies, 8th edition.983-988.

Brubacher J. Toxicon 1999; 37: 931-942

Cheung K. J Pediatr Child Health 1991; 27: 312-313.

Eddleston M. Lancet 2000; 355: 967-972

Flanagan RJ. Drug Saf 2004; 27: 1115-1133.

55

digoxin toxicity calcium use
Digoxin Toxicity: Calcium Use

Historically calcium has been contraindicated in digoxin-poisoned patients (often considered if patient also is poisoned by calcium channel blocker or is hyperkalemic)

  • Intracellular hypercalcemia is already present and additional calcium theoretically may result in synergistic cardiac effects with digoxin and result in hypercontractility or hypocontractility (“stone heart”) and cardiac arrest

However, a recent study did not support this theory.

Levine M, Nikkanen H, Pallin DJ. J of Emerg Med 2011; 40: 41-46.

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