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Digoxin Immune Fab (Ovine)

Class: Serums
ATC Class: C01AA05
VA Class: AD900
Brands: Digibind, DigiFab

Introduction

Antidote for digoxin toxicity; ovine immunoglobulin Fab fragments capable of binding digoxin.1 2 3 4 5 6 7 20 80

Uses for Digoxin Immune Fab (Ovine)

Digoxin Toxicity

Treatment of life-threatening or potentially life-threatening digoxin toxicity or overdosage.1 80 82 83 84 85 86 87

Has been used for treatment of life-threatening overdosage of digitoxin (no longer commercially available in US)1 82 or lanatoside C (not commercially available in US) intoxication;49 designated an orphan drug by FDA for treatment of potentially life-threatening cardiac glycoside (digitalis) intoxication refractory to conventional management.62

Not indicated for treatment of non-life-threatening cardiac glycoside intoxication;1 80 limited experience and consequences of repeated exposure to the immune Fab not known.1 80

Indicated in acute ingestions (e.g., known suicidal or accidental consumption) of ≥10 mg of digoxin in previously healthy adults or 4 mg (or >0.1 mg/kg) of digoxin in previously healthy children.1 80

Minimum toxic or lethal acute doses of digoxin not well established;56 acute digoxin ingestions of >10 mg in previously healthy adults or >4 mg in previously healthy children often result in cardiac arrest.1 68 74

Indicated in acute ingestions resulting in steady-state serum digoxin concentrations >10 ng/mL or chronic ingestions resulting in steady-state serum digoxin concentrations >6 ng/mL in adults or >4 ng/mL in children;80 ingestions resulting in steady-state serum digoxin concentrations >10 ng/mL often result in cardiac arrest.1

Indicated when there are manifestations of life-threatening digoxin toxicity, including severe ventricular arrhythmias (e.g., ventricular tachycardia or fibrillation), progressive bradycardia (e.g., second- or third-degree heart block not responsive to atropine), or serum potassium concentrations >5–5.5 mEq/L in adults or >6 mEq/L in children with rapidly progressive signs and symptoms of digoxin toxicity.1 80

Progressive hyperkalemia treated by conventional supportive and symptomatic measures without digoxin immune Fab (ovine) has poor prognosis.1 6 40 45 46 47 68 80 Also consider other potential causes of hyperkalemia, especially if digoxin immune Fab (ovine) does not appear to substantially decrease serum potassium concentrations.69

Poisonings Involving Cardiotoxic Plants and Other Substances

Has been used for treatment of poisonings involving ingestion of certain cardiotoxic plants, including common or pink oleander (Nerium oleander),79 87 92 yellow oleander (Thevetia peruviana),87 89 90 95 and Indian hemp (Apocynum cannabinum).87 Has reversed or improved cardiotoxicity in some individuals;79 87 89 90 95 additional study needed.92 95

Has not been effective in poisonings involving ingestion of foxglove extract79 or yew berry.79

Reversed or improved cardiotoxicity associated with ingestion of toad venom.94 Toad venom has been identified in illicit street drugs marketed as aphrodisiacs; contains several cardioactive steroids (bufadienolides), including bufalin, cinobufagin, cinobufotalin, and resibufogenin.87 94

Preeclampsia and Eclampsia

Has been used with some success for management of severe preeclampsia or eclampsia;109 110 111 112 116 designated an orphan drug by FDA for treatment of severe preeclampsia and eclampsia.62

Severe preeclampsia and eclampsia are major causes of maternal and fetal morbidity and mortality.109 110 111 112 113 115 116 118 There is some evidence that increased concentrations of endogenous cardiotonic steroids, including endogenous digitalis-like factors (EDLFs), in maternal and/or cord blood may contribute to pathogenesis of preeclampsia, particularly elevated BP;109 111 112 114 115 116 117 118 119 additional study needed to evaluate use of digoxin immune Fab (ovine).109 110 113 115 116

Digoxin Immune Fab (Ovine) Dosage and Administration

Administration

IV Administration

Administer by IV infusion.1 2 3 6 20 80

May be given by rapid IV injection if cardiac arrest is imminent, but not recommended for other patients since rapid injection may be associated with increased risk of infusion reactions or other adverse effects (e.g., allergic reactions).6 69 80

Digibind: Use 0.22-mcm inline membrane filter during IV infusion.1 68

DigiFab: Inline membrane filter not recommended.81

Reconstitution and Dilution of Digibind

Add 4 mL of sterile water for injection to vial containing 38 mg to provide solution containing 9.5 mg/mL;1 gently mix until dissolved.1

If desired, reconstituted solution may be diluted to a convenient volume with 0.9% sodium chloride injection.1

For infants or small children (≤20 kg), dose of reconstituted solution may be administered undiluted using a tuberculin syringe;1 for doses ≤3 mg, the reconstituted solution can be diluted with 34 mL of 0.9% sodium chloride to provide solution containing 1 mg/mL.1

Reconstitution and Dilution of DigiFab

Add 4 mL of sterile water for injection to vial containing 40 mg to provide solution containing 10 mg/mL;80 gently mix until dissolved.80

If desired, reconstituted solution may be diluted to a convenient volume with 0.9% sodium chloride injection.1

For infants or small children (≤20 kg), dose of reconstituted solution may be administered undiluted using a tuberculin syringe;1 for doses ≤3 mg, the reconstituted solution can be diluted with 36 mL of 0.9% sodium chloride to provide solution containing 1 mg/mL.1

Rate of Administration

Administer by IV infusion over at least 15–30 minutes.1 3 6 20 80

Slower IV infusion rates have been used (e.g., over 1–5 hours),2 20 32 49 69 73 82 but do not appear to offer any advantage and may delay response.49 69

Use rapid IV injection if cardiac arrest is imminent.1 6 80

Dosage

Dosage of digoxin immune Fab (ovine) varies according to amount of digoxin to be neutralized.1 2 3 6 20 80

One vial of Digibind (38-mg vial) or one vial of DigiFab (40-mg vial) neutralizes approximately 0.5 mg of digoxin.1 80 Because adult dosage (in mg) is rounded up to the next whole vial, dosage for adults and most children (in number of vials) is the same for both preparations.1 80 However, dosage for infants and small children (≤20 kg) varies depending on which preparation is used.1 80

When amount of digoxin ingested is unknown and cannot be estimated and when serum digoxin concentrations are unavailable, general dosage guidelines can be used and may be adequate to treat most life-threatening digoxin overdosages.1 80

If amount of digoxin ingested is known, dosage required to neutralize the cardiac glycoside can be calculated using estimated total body load (TBL) of digoxin, which takes into consideration amount (mg of digoxin) and bioavailability of digoxin preparation ingested.1 80 Alternatively, dosage can be calculated based on steady-state serum digoxin concentrations.1 80

When a calculated dosage is used, consider that an inaccurate estimate of amount of digoxin ingested or absorbed may occur if serum digoxin concentrations were not measured at steady state or were outside measurable limits of assay used (digoxin assay kits are designed to measure serum concentrations <5 ng/mL; dilution of serum sample required to accurately measure concentrations >5 ng/mL).1 80

Also consider that an average steady-state volume of distribution of digoxin (5 L/kg) is used to convert serum digoxin concentrations to TBL of digoxin in mg; however, volume of distribution of the drug may vary widely among individuals.1 69 80 Many patients may require a higher dosage for complete neutralization, and doses should be rounded up to the nearest whole vial.1 80

If dosage estimated based on the acute ingested dose of digoxin differs substantially from dosage calculated using serum digoxin concentration, it may be preferable to use the higher dosage.1 80

If toxicity is not adequately reversed several hours after the dose or if toxicity recurs, readministration may be necessary and clinical judgment should guide dosage selection.1 80

If there is no response to an adequate dose of digoxin immune fab (ovine), consider possibility that clinical problem is not caused by digoxin intoxication and re-evaluate diagnosis.1 80

Pediatric Patients

General Dosage for Digoxin Toxicity
Toxicity Following Acute Ingestion of Unknown Digoxin Amount
IV

Children: 760 mg Digibind or 800 mg DigiFab (20 vials of either) usually adequate for most life-threatening ingestions.1 80 Monitor small children (≤20 kg) for fluid overload.1 80

Alternatively, administer 380 mg Digibind or 400 mg DigiFab (10 vials of either), observe patient's response, and administer additional dose of 380 mg Digibind or 400 mg DigiFab (10 vials of either) if clinically indicated.1 80

Toxicity During Chronic Digoxin Therapy When Serum Digoxin Concentrations Are Unavailable
IV

Infants and small children (≤20 kg): 38 mg Digibind or 40 mg DigiFab (1 vial of either) usually sufficient.1 80

Calculated Dosage for Digoxin Toxicity
Toxicity Following Acute Ingestion of Known Digoxin Amount
IV

Dosage may be calculated based on amount of digoxin ingested and estimated TBL, taking into consideration bioavailability of preparation ingested.1 80 Digoxin tablets are 80% absorbed; digoxin liquid-filled capsules are 100% absorbed.1 80

For digoxin tablets: TBL (in mg) = amount (in mg) ingested x 0.8.1 80

For digoxin liquid-filled capsules or IV digoxin: TBL (in mg) = 100% of amount (in mg) ingested or infused (i.e., do not multiply by 0.8).1 68 80

Since each vial of Digibind or DigiFab binds approximately 0.5 mg of digoxin, dosage (in no. of vials) is calculated by dividing TBL (in mg) by 0.5.1 80

Dosage (in no. of vials) = TBL (in mg) / 0.5 (mg of digitalis bound/vial)1 80

Alternatively, for children who have ingested a single large digoxin dose (as 0.25-mg tablets or 0.2-mg liquid-filled capsules) and when approximate number of tablets or capsules ingested is known, approximate dosage (in no. of vials) can be estimated using Table 1.1 80

Table 1. Approximate Dosage of Digoxin Immune Fab (Ovine) for Children Based on Acute Ingested Digoxin Dose180

Dosage of Digoxin Immune Fab (Ovine)

Number of Digoxin 0.25-mg Tablets or 0.2-mg Liquid-filled Capsules Ingested

Number of 38-mg Vials (Digibind)

Number of 40-mg Vials (DigiFab)

25

380 mg (10 vials)

400 mg (10 vials)

50

760 mg (20 vials)

800 mg (20 vials)

75

1140 mg (30 vials)

1200 mg (30 vials)

100

1520 mg (40 vials)

1600 mg (40 vials)

150

2280 mg (60 vials)

2400 mg (60 vials)

200

3040 mg (80 vials)

3200 mg (80 vials)

Toxicity During Chronic Therapy When Serum Digoxin Concentrations Are Known
IV

Infants and small children (≤20 kg): Calculate dosage as mg of digoxin immune Fab (ovine), not as no. of vials.1 80

Calculate dosage (in no. of vials) based on steady-state serum digoxin concentrations by multiplying serum digoxin concentration (in ng/mL) by patient's weight (kg) and dividing by 100.1 80

Dosage (in no. of vials) = [Conc of digoxin (in ng/mL) × body weight (in kg)]/100

Calculate dosage (in mg) by multiplying the dosage (in no. of vials) by 38 mg/vial (Digibind) or by 40 mg/vial (DigiFab).1 80

Dosage of Digibind (in mg) = [Conc of digoxin (in ng/mL) × body weight (in kg) × 38 mg/vial]/100

Dosage of DigiFab (in mg) = [Conc of digoxin (in ng/mL) × body weight (in kg) × 40 mg/vial]/100

Alternatively, for infants and small children (≤20 kg), dosage (in mg) can be estimated based on patient's weight and steady-state serum digoxin concentrations (see Table 2 and Table 3).1 80

Table 2. Estimated Dosage of Digibind (in mg) for Infants and Small Children Based on Steady-state Serum Digoxin Concentration1

Dosage (in mg) at Specified Steady-state Serum Digoxin Concentration (ng/mL)

Body Weight (kg)

1

2

4

8

12

16

20

1

0.4

1

1.5

3

5

6

8

3

1

2

5

9

14

18

23

5

2

4

8

15

23

30

38

10

4

8

15

30

46

61

76

20

8

15

30

61

91

122

152

Table 3. Estimated Dosage of DigiFab (in mg) for Infants and Small Children Based on Steady-state Serum Digoxin Concentration.80

Dosage (in mg) at Specified Steady-state Serum Digoxin Concentration (ng/mL)

Body Weight (kg)

1

2

4

8

12

16

20

1

0.4

1

1.5

3

5

6.5

8

3

1

2.5

5

10

14

19

24

5

2

4

8

16

24

32

40

10

4

8

16

32

48

64

80

20

8

16

32

64

96

128

160

Adults

General Dosage for Digoxin Toxicity
Toxicity Following Acute Ingestion of Unknown Digoxin Amount
IV

760 mg Digibind or 800 mg DigiFab (20 vials of either) usually adequate for most life-threatening ingestions.1 80

Alternatively, administer 380 mg Digibind or 400 mg DigiFab (10 vials of either), observe patient's response, and administer additional dose of 380 mg Digibind or 400 mg DigiFab (10 vials of either) if clinically indicated. 1 80

Toxicity During Chronic Therapy When Serum Digoxin Concentrations Are Unknown
IV

228 mg Digibind or 240 mg DigiFab (6 vials of either) usually sufficient.1 80

Calculated Dosage for Digoxin Toxicity
Toxicity Following Acute Ingestion of Known Digoxin Amount
IV

Dosage may be calculated based on amount of digoxin ingested and estimate of TBL, taking into consideration bioavailability of preparation ingested.1 80 Digoxin tablets are 80% absorbed; digoxin liquid-filled capsules are 100% absorbed.1 80

For digoxin tablets: TBL (in mg) = amount (in mg) ingested x 0.8.1 80

For digoxin liquid-filled capsules and IV digoxin: TBL (in mg) = 100% of the amount (in mg) ingested or infused (i.e., do not multiply by 0.8).1 68 80

Since each vial of Digibind or DigiFab binds approximately 0.5 mg of digoxin, dosage (in no. of vials) is calculated by dividing the TBL (in mg) by 0.5.1 80

Dosage (in no. of vials) = TBL (in mg) / 0.5 (mg of digitalis bound/vial)

Alternatively, for adults who have ingested a single large digoxin dose (as 0.25-mg tablets or 0.2-mg liquid-filled capsules) and when approximate number of tablets or capsules ingested is known, approximate dosage (in no. of vials) can be estimated using Table 4.1 80

Table 4. Approximate Dosage of Digoxin Immune Fab (Ovine) for Adults Based on Acute Ingested Digoxin Dose180

Dosage of Digoxin Immune Fab (Ovine)

Number of Digoxin 0.25-mg Tablets or 0.2-mg Liquid-filled Capsules Ingested

Number of 38-mg Vials (Digibind)

Number of 40-mg Vials (DigiFab)

25

380 mg (10 vials)

400 mg (10 vials)

50

760 mg (20 vials)

800 mg (20 vials)

75

1140 mg (30 vials)

1200 mg (30 vials)

100

1520 mg (40 vials)

1600 mg (40 vials)

150

2280 mg (60 vials)

2400 mg (60 vials)

200

3040 mg (80 vials)

3200 mg (80 vials)

Toxicity During Chronic Therapy When Serum Digoxin Concentrations Are Known
IV

Calculate dosage (in no. of vials) based on steady-state serum digoxin concentrations by multiplying serum digoxin concentration (in ng/mL) by patient's weight (kg) and dividing by 100.1 80

Dosage (in no. of vials) = [Conc of digoxin (in ng/mL) × body weight (in kg)]/100

Alternatively, dosage (in mg) can be estimated based on patient's weight and steady-state serum digoxin concentrations (see Table 5).1 80

Table 5. Estimated Dosage of Digoxin Immune Fab (Ovine) (in no. of vials) for Adults Based on Steady-state Serum Digoxin Concentration180

Dosage (in no. of vials) at Specified Steady-state Serum Digoxin Concentration (ng/mL)

Body Weight (kg)

1

2

4

8

12

16

20

40

0.5

1

2

3

5

7

8

60

0.5

1

3

5

7

10

12

70

1

2

3

6

9

11

14

80

1

2

3

7

10

13

16

100

1

2

4

8

12

16

20

Prescribing Limits

Pediatric Patients

IV

Maximum dose and maximum total dosage not known.80

Adults

IV

Maximum dose and maximum total dosage not known.80

Special Populations

Hepatic Impairment

No specific dosage recommendations.1 80

Renal Impairment

Dosage adjustment not required.1 97 (See Renal Impairment under Cautions.)

Geriatric Patients

No age-related dosage adjustment required.1 (See Geriatric Use under Cautions.)

Cautions for Digoxin Immune Fab (Ovine)

Contraindications

  • Digibind: Manufacturer states none.1

  • DigiFab: Manufacturer states none, but states do not use in patients with known hypersensitivity to papaya or papain unless benefits outweigh risks.80 (See Papain Hypersensitivity under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Consider possibility of hypersensitivity reactions (including anaphylaxis or anaphylactoid reactions), delayed allergic reactions, or febrile reactions.1 80

Carefully monitor for signs and symptoms of acute allergic reaction (e.g., urticaria, pruritus, erythema, angioedema, bronchospasm with wheezing or cough, stridor, laryngeal edema, hypotension, tachycardia).80 If allergic reaction occurs, immediately discontinue digoxin immune Fab (ovine) and initiate appropriate therapy (e.g., oxygen, volume expansion, diphenhydramine, corticosteroids, airway management).1 80 Balance need for epinephrine against potential risk in the setting of digitalis toxicity.1 80

Patients with known allergies (especially to antibiotics or sheep proteins) and those who have previously received intact ovine antibodies or ovine Fab are at greatest risk for sensitivity reactions.1 80

Because digoxin immune Fab (ovine) lacks antigenic Fc fragment, it should be less immunogenic than intact immunoglobulin; however, additional clinical experience needed to fully determine immunogenic risk.1 2 3 4 5 6 17 20 25 51 63 80

Papain Hypersensitivity

Traces of papain or inactivated papain residues may be present in digoxin immune Fab (ovine);1 papain is used in manufacturing process to cleave whole antibody into Fab and Fc fragments.1 80

Individuals allergic to papain, chymopapain, other papaya extracts, or the pineapple enzyme bromelain may be at risk of hypersensitivity reactions to digoxin immune Fab (ovine).1 80 Patients allergic to dust mites or latex may also be allergic to papain.80

Do not use in patients with history of hypersensitivity to papaya or papain unless benefits outweigh risks;80 keep appropriate treatments for anaphylaxis readily available.80

Human Anti-ovine Fab Antibodies

Patients may develop ovine Fab-specific antibodies after receiving digoxin immune Fab (ovine).80

In patients retreated with digoxin immune Fab (ovine), a decrease in drug efficacy secondary to the presence of human antibodies against ovine Fab theoretically may occur.80 However, there have been no clinical reports of reduction in binding or neutralization response,80 and clinical importance relative to safety and efficacy of the immune Fab not fully determined.80

Sensitivity Testing

Sensitivity testing not routinely recommended prior to administration of digoxin immune Fab (ovine) since such testing may delay urgently needed treatment.1 80

Manufacturer of DigiFab states sensitivity testing not recommended and has not been shown to be useful in predicting allergic responses to digoxin immune Fab (ovine).80

Manufacturer of Digibind states sensitivity testing may be appropriate for patients at higher risk, especially those with known allergies and those previously exposed to digoxin immune Fab (ovine).1 If sensitivity testing considered appropriate, perform intradermal or scratch test using 1:100 dilution of reconstituted Digibind.1 Add 4 mL of sterile water for injection to vial containing 38 mg of digoxin immune Fab (ovine) and gently mix to dissolve; prepare 1:100 dilution by withdrawing 0.1 mL of reconstituted solution and further diluting in 9.9 mL of 0.9% sodium chloride to provide solution containing 95 mcg/mL.1

Intradermal test: Inject 0.1 mL of 1:100 dilution (i.e., 9.5 mcg) into dermis.1

Scratch test: Place 1 drop of 1:100 dilution on the skin, then make a 0.64 cm (¼ inch) scratch through the drop.1

To facilitate interpretation, perform control test using 0.9% sodium chloride on opposite extremity.68 Read test site after 20 minutes; positive reaction consists of urticarial wheal and surrounding edema.1 Negative history of allergy and negative skin test do not preclude possibility of immediate sensitivity reaction or delayed serum sickness.69

If systemic reaction occurs during skin testing, apply tourniquet proximal to test site and institute measures to treat anaphylaxis.1

If positive sensitivity test or systemic reaction occurs, weigh risk of administering digoxin immune Fab (ovine) against risk of withholding the immune Fab, taking into account that cardiac glycoside intoxication may be fatal.1 68 69 Avoid further doses unless absolutely essential.1

If administered to patient with positive sensitivity test, pretreat with antihistamine (e.g., diphenhydramine) and corticosteroid; keep equipment and agents immediately available for adequate airway maintenance and treatment of anaphylaxis and other severe systemic reactions.1 68 69

Suicidal Ingestion

Suicidal ingestion often involves multiple drugs; in patients with known or suspected suicidal ingestion of digoxin, consider toxic effects of other drugs, especially if toxicity is not reversed by digoxin immune Fab (ovine).1 80

Cardiovascular Effects

Potential worsening of low cardiac output states and CHF, possibly by decreasing effective inotropic concentrations of digoxin;1 3 6 7 26 30 80 causal relationship not established.6

May consider use of inotropic agents (e.g., dopamine or dobutamine) or vasodilators if cardiac output decreases during digoxin immune Fab (ovine) therapy;1 use sympathomimetic drugs cautiously since they may exacerbate or precipitate cardiac glycoside-induced ventricular arrhythmias.1 24 28 80

Do not use cardiac glycosides to increase cardiac output in patients with documented cardiac glycoside intoxication.1 80

Patients with preexisting atrial fibrillation may develop a rapid ventricular response secondary to reversal of the effects of cardiac glycosides on the AV node.1 2 6 80

Use with caution in patients with intrinsically poor cardiac function; deterioration may occur from withdrawal of the inotropic action of digoxin.1 80

Monitor closely during and after administration of digoxin immune Fab; periodically monitor body temperature, BP, and ECG.1 80

Do not attempt redigitalization until digoxin immune Fab (ovine) elimination is complete (i.e., several days in normal renal function and ≥1 week in renal insufficiency).1 80 (See Renal Impairment under Cautions.)

General Supportive Measures and Serum Digoxin Monitoring

Immediately discontinue cardiac glycoside;1 80 correct fluid and electrolyte disturbances (especially hyperkalemia), acid-base imbalances, and hypoxia.1 22 23 24 48 80 (See Cardiovascular Effects and also see Hypokalemia and Hyperkalemia under Cautions.)

Whenever possible, obtain serum digoxin concentrations prior to initiating digoxin immune Fab (ovine).1 2 5 6 80 Digoxin immune Fab (ovine) causes rapid rise in total serum digoxin concentration, consisting almost completely of the Fab-bound, pharmacologically inactive form of the glycoside.1 2 4 6 20 80 (See Specific Drugs and Laboratory Tests under Interactions.)

Hypokalemia and Hyperkalemia

Monitor serum potassium concentrations frequently during and after administration of digoxin immune Fab (ovine), especially during first several hours after the dose.1 2 37 80 Hypokalemia or hyperkalemia may develop rapidly.1 2 22 23 24 34 39 50 56 57 80

Advanced cardiac glycoside toxicity can cause life-threatening hyperkalemia by increasing extracellular potassium and/or by inhibiting potassium movement into cells.1 6 29 45 46 47 80 May result in increased renal excretion of potassium; patient may appear hyperkalemic while having a total body deficit of potassium.1 80 Digoxin immune Fab (ovine) reverses the effect of glycoside toxicity and potassium shifts back into the cells, resulting in hypokalemia.1 6 29 45 80

Occasionally, may need to treat hypokalemia; however, treat cautiously since hyperkalemia may develop rapidly in advanced intoxication.1 2 22 23 24 50 56 57 80

Specific Populations

Pregnancy

Category C.1 80

Lactation

Not known whether digoxin immune Fab (ovine) is distributed into milk.1 80 Use with caution in nursing women.1 80

Pediatric Use

Has been used in limited number of infants and children without unusual adverse effects.1 3 6 20 23 31 33 35 36 38 80 Weigh benefits of treatment against potential risks.1 80

Geriatric Use

No overall differences in safety or efficacy relative to younger adults; possibility exists of greater sensitivity to the immune Fab in some geriatric individuals.1 80

Use with caution due to greater frequency of decreased renal function.1 80 Monitor renal function and observe for possible recurrence of toxicity.1 80 (See Renal Impairment under Cautions.)

Renal Impairment

Use with caution; decreased clearance of Fab fragment-digoxin complex in renal dysfunction.1 6 80

Unclear if reintoxication could occur in severe renal failure following release of newly unbound digoxin into the blood.1 80 Consider monitoring free (unbound) digoxin concentrations to detect reintoxication.1 80

Dosage does not need to be reduced,1 97 but monitor patients with renal impairment, especially functionally anephric patients, for prolonged period of time for possible recurrence of digitalis toxicity.1 80 97 101 104 (See Special Populations under Pharmacokinetics.)

Delay redigitalization until elimination of digoxin immune Fab (ovine) is complete; may require ≥1 week in patients with renal insufficiency.1 (See Cardiovascular Effects under Cautions.)

Interactions for Digoxin Immune Fab (Ovine)

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Cardiac glycosides (e.g., digoxin, digitoxin, lanatoside C)

Digoxin immune Fab (ovine) binds cardiac glycosides rendering them therapeutically inactive1 5 7 17 49 80

Postpone redigitalization until Fab fragments eliminated from the body1 80 (See Cardiovascular Effects and also see Renal Impairment under Cautions)

Serum cardiac glycoside radioimmunoassay

Digoxin immune Fab (ovine) falsely increases or decreases results1 2 6 52 75 76 80 106 107

Total serum glycoside concentrations may be increased 10- to 20-fold; consists almost completely of Fab-bound, pharmacologically inactive form of the glycoside1 2 4 6 14 20 80

Collect serum to determine digoxin concentration prior to administration of digoxin immune Fab (ovine)1 2 5 6 80

Results affected until Fab fragments eliminated from body1 6 52 75 76 80

Digoxin Immune Fab (Ovine) Pharmacokinetics

Absorption

Onset

Peak serum concentrations occur at completion of IV infusion.2 25

Rapidly binds to serum glycoside; serum concentrations of free (unbound) glycoside decline to undetectable levels within several minutes following completion of IV infusion.5 6 20 22 42 43 71 73

Improvement in signs and symptoms of cardiac glycoside toxicity generally apparent within 30 minutes after completion of IV infusion;1 3 6 37 however, onset of response is variable and may depend on infusion rate, dose, and other factors.6 68 69 73

Cardiac rhythm (e.g., ventricular fibrillation, other severe arrhythmias) may stabilize in 0.5–13 hours after initial dose.20

Reversal of cardiac glycoside toxicity, including hyperkalemia, often complete within 2–6 hours.6 17 34 37 39 68 69 72 80 73 80

Duration

Serum concentrations of free (unbound) glycoside remain low for 8–12 hours after completion of IV infusion.6 20 68 Decline in free serum glycoside concentration correlates clinically to toxicity reversal.2 3 6 7 21 23 45

Distribution

Extent

Rapidly distributes throughout the extracellular space, into both plasma and interstitial fluid.2 7 17 20 21 27 Intracellular distribution may occur; additional study needed.25 68 73

Not known whether digoxin immune Fab (ovine) crosses the placenta or is distributed into human milk.1 80

Elimination

Elimination Route

Excreted in urine via glomerular filtration, principally as the cardiac glycoside-Fab fragment complex in intoxicated patients.1 7 20 21 73 80

Hemodialysis and peritoneal dialysis appear to have no effect or only very minimal effect on removal of digoxin-immune Fab (ovine).101 104 105

Half-life

Biphasic; elimination half-life 14–20 hours.1 2 6 25 27 73 80

Special Populations

Patients with renal impairment: Terminal elimination half-life reported to be 25–137 hours;97 101 half-life may be increased up to tenfold.80

Functionally anephric patients may be unable to clear Fab fragment-digoxin complex by glomerular filtration and renal excretion.1 (See Renal Impairment under Cautions.)

Stability

Storage

Parenteral

Powder for Injection

2–8°C.1 80 Digibind may be stored at up to 30°C for up to 30 days.1 Do not freeze.80

Use immediately following reconstitution, but may refrigerate at 2–8°C for up to 4 hours.1 80

Actions

  • Monovalent, digoxin-specific antigen binding fragments (Fab) derived from antidigoxin antibodies1 2 3 4 5 7 8 9 10 20 51 80 obtained from serum of immunized sheep (ovine).1 2 3 4 8 9 10 20 68 80

  • Binds to free (unbound) digoxin intravascularly and in extracellular fluid;1 2 5 6 11 12 17 20 29 51 63 70 71 prevents and reverses pharmacologic and toxic effects of digoxin, including biochemical and cardiac effects.1 2 3 4 5 6 7 8 12 17 20 26 27 28 29 30 31 32 33 34 35 36 37 38 39 49 51 55 66 70 71 80

  • Reverses toxicity induced by digitoxin (no longer commercially available in US). 1 3 13 14 15 16 18 19 20 80

  • Binds to other digoxin derivatives (e.g., β-methyldigoxin, β-acetyldigoxin),31 32 some of the cardioactive metabolites of digoxin,7 and possibly some other cardiac glycosides (e.g., lanatoside C).49

  • May bind to oleander glycosides.67 68 69

  • In vitro studies indicate that digoxin immune Fab (ovine) may cross-react with and bind to endogenous cardiotonic steroids, including endogenous digitalis-like factors (EDLFs), identified in maternal and/or cord blood from women with preeclampsia.115 118

Advice to Patients

  • Advise patients of the possibility of anaphylactic reactions during and after infusion.80

  • Importance of informing clinicians of allergy history, including antibiotics, sheep proteins, papaya, papain, chymopapain, other papaya extracts, the pineapple enzyme bromelain, dust mites, or latex.1 80

  • Importance of informing clinicians of any previous exposure to antibodies or Fab fragments derived from sheep serum.1 80

  • Importance of immediately informing clinician if any signs and symptoms of delayed allergic reaction or serum sickness (e.g., rash, hives, itching) occur after hospital discharge.1 80

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 80

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 80

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Digoxin Immune Fab (Ovine)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

38 mg

Digibind

GlaxoSmithKline

40 mg

DigiFab

Protherics

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Date published: April 16, 2013
Last reviewed: April 16, 2013
Date modified: February 08, 2016

References

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