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Digoxin Immune Fab

Pronunciation

(di JOKS in i MYUN fab)

Index Terms

  • Antidigoxin Fab Fragments, Ovine
  • Digibind

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

DigiFab: 40 mg (1 ea)

Brand Names: U.S.

  • DigiFab

Pharmacologic Category

  • Antidote

Pharmacology

Digoxin immune antigen-binding fragments (Fab) are specific antibodies for the treatment of digitalis intoxication in carefully selected patients; binds with molecules of digoxin or DIGIToxin and is then excreted by the kidneys and removed from the body

Distribution

Vd: 0.3 L/kg

Excretion

Urine (concentrations declining within 5 to 7 days)

Onset of Action

IV: Digitalis toxicity: Improvement may be seen within 20 to 90 minutes (Betten, 2006)

Half-Life Elimination

15 to 20 hours; may be increased up to 10-fold in patient with renal impairment

Use: Labeled Indications

Digoxin toxicity: Treatment of life-threatening or potentially life-threatening digoxin intoxication, including:

- Acute digoxin ingestion (≥10 mg in adults; 4 mg [>0.1 mg/kg] in children); resulting in serum concentration ≥10 ng/mL)

- Chronic ingestion leading to steady state digoxin concentrations >6 ng/mL in adults or >4 ng/mL in children

- Manifestations of life-threatening digoxin toxicity due to overdose (severe ventricular arrhythmias, progressive bradycardia, second or third degree heart block not responsive to atropine, serum potassium concentration >5.5 mEq/L in adults or >6 mEq/L in children)

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Dosing: Adult

Each vial of digoxin immune Fab 40 mg will bind ~0.5 mg of digoxin or DIGIToxin.

Digoxin toxicity: Note: Estimation of the dose is based on the body burden of digitalis. This may be calculated if the amount ingested is known or the post-distribution serum drug level is known (round the dose up to the nearest whole vial). If the amount ingested is unknown, general dosing guidelines should be used.

Acute ingestion of unknown amount: IV: Initial: 10 vials; if needed, administer a second dose of 10 vials (20 vials total is adequate to treat most life-threatening ingestions).

Acute ingestion of known amount: IV:

Based on number of tablets or capsules ingested:

Step 1: Calculate total body load (mg)

Digoxin capsules or DIGIToxin:

Total body load (mg) = Amount (mg) digoxin capsules or DIGIToxin ingested

Digoxin tablets:

Total body load (mg) = 0.8 x (amount [mg] digoxin tablets ingested)

Step 2: Calculate number of vials needed

Digoxin Immune Fab Dose (vials) = Total body load (mg) / (0.5)

Alternatively, the following table gives an estimation of the number of vials needed based on the number of digoxin tablets or capsules ingested.

Approximate Dose of Digoxin Immune Fab (in vials) for Reversal of a Single Large Digoxin Overdose

Number of Digoxin Tablets or Capsules Ingested1

Dose of Digoxin Immune Fab

(# of Vials)

1250 mcg tablets with 80% bioavailability or 200 mcg capsules with 100% bioavailability.

25

10

50

20

75

30

100

40

150

60

200

80

Table has been converted to the following text.

Number of digoxin tablets or capsules ingested1: 25

Dose of digoxin immune fab: 10 vials

Number of digoxin tablets or capsules ingested1: 50

Dose of digoxin immune fab: 20 vials

Number of digoxin tablets or capsules ingested1: 75

Dose of digoxin immune fab: 30 vials

Number of digoxin tablets or capsules ingested1: 100

Dose of digoxin immune fab: 40 vials

Number of digoxin tablets or capsules ingested1: 150

Dose of digoxin immune fab: 60 vials

Number of digoxin tablets or capsules ingested1: 200

Dose of digoxin immune fab: 80 vials

1250 mcg tablets with 80% bioavailability or 200 mcg capsules with 100% bioavailability.

Based on steady-state serum digoxin concentration: Adults:

Digoxin Immune Fab Dose (vials) = (serum digoxin concentration [ng/mL] x weight [kg]) / 100

Alternatively, the following table gives an estimation of the number of vials needed based on the steady-state serum digoxin concentration.

Adult Dose Estimates of Digoxin Immune Fab (in # of Vials) From Steady-State Serum Digoxin Concentration

Patient Weight (kg)

Serum Digoxin Concentration (ng/mL)

1

2

4

8

12

16

20

40

0.5 vial

1 vial

2 vials

3 vials

5 vials

7 vials

8 vials

60

0.5 vial

1 vial

3 vials

5 vials

7 vials

10 vials

12 vials

70

1 vial

2 vials

3 vials

6 vials

9 vials

11 vials

14 vials

80

1 vial

2 vials

3 vials

7 vials

10 vials

13 vials

16 vials

100

1 vial

2 vials

4 vials

8 vials

12 vials

16 vials

20 vials

Table has been converted to the following text.

Adult Dose Estimates of Digoxin immune Fab (in # of Vials) From Steady-State Serum Digoxin Concentration

Patient Weight (kg): Serum Digoxin Concentration (ng/mL): Digoxin immune Fab (in # of Vials)

40 kg

1 ng/mL: 0.5 vial

2 ng/mL: 1 vial

4 ng/mL: 2 vials

8 ng/mL: 3 vials

12 ng/mL: 5 vials

16 ng/mL: 7 vials

20 ng/mL: 8 vials

60 kg

1 ng/mL: 0.5 vial

2 ng/mL: 1 vial

4 ng/mL: 3 vials

8 ng/mL: 5 vials

12 ng/mL: 7 vials

16 ng/mL: 10 vials

20 ng/mL: 12 vials

70 kg

1 ng/mL: 1 vial

2 ng/mL: 2 vials

4 ng/mL: 3 vials

8 ng/mL: 6 vials

12 ng/mL: 9 vials

16 ng/mL: 11 vials

20 ng/mL: 14 vials

80 kg

1 ng/mL: 1 vial

2 ng/mL: 2 vials

4 ng/mL: 3 vials

8 ng/mL: 7 vials

12 ng/mL: 10 vials

16 ng/mL: 13 vials

20 ng/mL: 16 vials

100 kg

1 ng/mL: 1 vial

2 ng/mL: 2 vials

4 ng/mL: 4 vials

8 ng/mL: 8 vials

12 ng/mL: 12 vials

16 ng/mL: 16 vials

20 ng/mL: 20 vials

Based on steady-state DIGIToxin concentration: If the calculated dose based on the DIGIToxin concentration is different from the estimated dose based on the known ingested amount (if available), use the higher dose.

Digoxin Immune Fab Dose (vials) = [serum DIGIToxin concentration (ng/mL) x weight (kg)] / 1000

Chronic toxicity (serum digoxin concentration unavailable): IV: Adults: 6 vials is adequate to reverse most cases of toxicity

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Each vial of digoxin immune Fab 40 mg will bind ~0.5 mg of digoxin or DIGIToxin.

Digoxin toxicity: Note: Estimation of the dose is based on the body burden of digitalis. This may be calculated if the amount ingested is known or the post-distribution serum drug level is known (round the dose up to the nearest whole vial). If the amount ingested is unknown, general dosing guidelines should be used.

Acute ingestion of unknown amount: IV: Refer to adult dosing.

Acute ingestion of known amount: IV: Refer to adult dosing.

Based on steady-state serum digoxin concentration:

Infants and Children ≤20 kg: May require smaller doses; calculate the dose in milligrams (mg).

Digoxin Immune Fab Dose (mg) = [(serum digoxin concentration [ng/mL] x weight [kg]) / 100] x (digoxin immune Fab amount per vial [mg/vial])

Note: Digoxin immune Fab amount per vial: 40 mg/vial.

Alternatively, the following table gives an estimation of the amount of digoxin immune Fab needed based on the steady-state serum digoxin concentration.

Infants and Small Children Dose Estimates of Digoxin Immune Fab (in mg) From Steady-State Serum Digoxin Concentration

Patient Weight

(kg)

Serum Digoxin Concentration (ng/mL)

1

2

4

8

12

16

20

1Dilution of reconstituted vial to 1 mg/mL may be desirable.

1

0.4 mg1

1 mg1

1.5 mg1

3 mg1

5 mg

6.5 mg

8 mg

3

1 mg1

2.5 mg1

5 mg

10 mg

14 mg

19 mg

24 mg

5

2 mg1

4 mg

8 mg

16 mg

24 mg

32 mg

40 mg

10

4 mg

8 mg

16 mg

32 mg

48 mg

64 mg

80 mg

20

8 mg

16 mg

32 mg

64 mg

96 mg

128 mg

160 mg

Table has been converted to the following text.

Infants and Small Children Dose Estimates of Digoxin Immune Fab (in mg) From Steady-State Serum Digoxin Concentration

Based on Patient Weight in Kilograms

Patient Weight (kg): Serum Digoxin Concentration (ng/mL): Digoxin Immune Fab dose (mg)

1 kg

1 ng/mL: 0.4 mg1

2 ng/mL: 1 mg1

4 ng/mL: 1.5 mg1

8 ng/mL: 3 mg1

12 ng/mL: 5 mg

16 ng/mL: 6.5 mg

20 ng/mL: 8 mg

3 kg

1 ng/mL: 1 mg1

2 ng/mL: 2.5 mg1

4 ng/mL: 5 mg

8 ng/mL: 10 mg

12 ng/mL: 14 mg

16 ng/mL: 19 mg

20 ng/mL: 24 mg

5 kg

1 ng/mL: 2 mg1

2 ng/mL: 4 mg

4 ng/mL: 8 mg

8 ng/mL: 16 mg

12 ng/mL: 24 mg

16 ng/mL: 32 mg

20 ng/mL: 40 mg

10 kg

1 ng/mL: 4 mg

2 ng/mL: 8 mg

4 ng/mL: 16 mg

8 ng/mL: 32 mg

12 ng/mL: 48 mg

16 ng/mL: 64 mg

20 ng/mL: 80 mg

20 kg

1 ng/mL: 8 mg

2 ng/mL: 16 mg

4 ng/mL: 32 mg

8 ng/mL: 64 mg

12 ng/mL: 96 mg

16 ng/mL: 128 mg

20 ng/mL: 160 mg

1Dilution of reconstituted vial to 1 mg/mL may be desirable.

Children >20 kg and Adolescents: Refer to adult dosing.

Based on steady-state DIGIToxin concentration: Refer to adult dosing.

Chronic toxicity (serum digoxin concentration unavailable): IV:

Infants and Children <20 kg: 1 vial is adequate to reverse most cases of toxicity

Children ≥20 kg and Adolescents: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling; however, use with caution since digoxin-digoxin immune Fab complex is renally eliminated. Patients should undergo prolonged monitoring for recurrence of toxicity.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling.

Reconstitution

Reconstitute each vial to a concentration of 10 mg/mL by adding 4 mL SWFI; gently mix. Add reconstituted digoxin immune fab to an appropriate volume of NS. For very small doses, the reconstituted vial can be further diluted by adding an additional 36 mL NS to achieve a final concentration of 1 mg/mL. Infants and small children who require very small doses may be administered reconstituted digoxin immune undiluted using a tuberculin syringe.

Administration

Administer by slow IV infusion over at least 30 minutes. May also be given by bolus injection if cardiac arrest is imminent (infusion-related reaction may occur). Infants and small children who require very small doses can be administered reconstituted digoxin immune fab undiluted using a tuberculin syringe. Stopping the infusion and restarting at a slower rate may help if an infusion-related reaction occurs.

Storage

Store vials at 2°C to 8°C (36°F to 46°F); do not freeze. Reconstituted solutions are stable for 4 hours when stored at 2°C to 8°C (36°F to 46°F). The following stability information has also been reported: May be stored at room temperature for up to 30 days (Cohen, 2007).

Drug Interactions

There are no known significant interactions.

Test Interactions

Digoxin immune fab may interfere with digitalis immunoassay measurements, thereby resulting in clinically misleading total serum digoxin concentrations until all Fab fragments are eliminated from the body (may take several days to >1 week after administration). Digoxin serum samples should be obtained before digoxin immune fab administration, if possible.

Adverse Reactions

Frequency not defined.

Cardiovascular: Orthostatic hypotension, phlebitis, ventricular tachycardia (patients with atrial fibrillation; due to digoxin withdrawal), worsening of heart failure (due to digoxin withdrawal)

Endocrine & metabolic: Hypokalemia

Hypersensitivity: Hypersensitivity reaction, serum sickness

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Digoxin immune Fab is derived from ovine (sheep) Fab immunoglobulin fragments; hypersensitivity reactions (eg, anaphylactic or anaphylactoid reactions, delayed allergic reactions) are possible. Patients with allergies to sheep proteins and patients with prior exposure to ovine antibodies or ovine Fab may be at a higher risk for anaphylactic reactions. In patients who develop an anaphylactic reaction, discontinue the infusion immediately and administer emergency care; balance the need for epinephrine against its potential risk in the setting of digitalis toxicity.

Processed with papain and may cause hypersensitivity reactions in patients allergic to papaya, other papaya extracts, papain, chymopapain, or the pineapple-enzyme bromelain. There may also be cross allergenicity with dust mite and latex allergens.

• Potassium imbalance: Patients experiencing acute digitalis toxicity may present with significant hyperkalemia due to shifting of potassium into the extracellular space. Upon treatment with digoxin immune Fab, potassium shifts back into the intracellular space and may result in hypokalemia. Monitor potassium closely, especially during the first few hours after administration; treat hypokalemia cautiously when clinically indicated.

Disease-related concerns:

• Heart failure (HF): In patients chronically maintained on digoxin for HF, administration of digoxin immune Fab may result in exacerbation of HF symptoms due to a reduction in digoxin serum concentration. If reinitiation is required, consider postponing until Fab fragments have been eliminated completely; elimination may take several days or longer, especially in patients with renal impairment.

• Renal impairment: Use with caution in patients with renal failure (experience limited); the Fab-digoxin complex will be eliminated more slowly. Toxicity may recur; prolonged monitoring for recurrence of symptoms and evaluation of free (unbound) digoxin concentrations (if test available) may be warranted in this patient population.

Monitoring Parameters

Prior to the first dose of digoxin immune Fab evaluate serum potassium, serum digoxin concentration, and serum creatinine; closely monitor serum potassium (eg, hourly for 4-6 hours; at least daily thereafter), temperature, blood pressure, and electrocardiogram after administration. Total serum digoxin concentrations will rise precipitously following administration of digoxin immune Fab due to the presence of the Fab-digoxin complex; because digoxin bound to Fab fragments cannot result in toxicity, this rise has no clinical meaning. Therefore, avoid monitoring total serum digoxin concentrations until the Fab fragments have been eliminated completely; this may be several days to weeks in patients with renal impairment (Ujhelyi, 1995). Monitor for volume overload in children < 20 kg. Monitor for signs and symptoms of a hypersensitivity reaction.

Patients with renal failure may experience a recurrence of toxicity; prolonged monitoring for recurrence of symptoms and evaluation of free (unbound) digoxin concentrations (if test available) may be warranted in this patient population.

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. In general, medications used as antidotes should take into consideration the health and prognosis of the mother; antidotes should be administered to pregnant women if there is a clear indication for use and should not be withheld because of fears of teratogenicity (Bailey, 2003).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber severe dizziness, passing out, tachycardia, cough, or signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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