Pharmacopeia

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Field N-ACETYL CYSTEINE (NAC)
Antidotes · Antidotes · Level 3
DIGOXIN ANTIBODIES
Antidotes · Antidotes · Level 3
Intralipid 20%
Antidotes · Antidotes · Level 3
Mechanism of action

- Metabolized to cysteine → Regeneration of sulphydril groups and glutathione
- acting as an alternate substrate for conjugation
- reduces disulfide bonds in mucoproteins

Binds excess digoxin or digitoxin molecules circulating in the blood
- Fab fragment-digoxin complex excreted by kidney - Net shifts the equilibrium away from binding of digoxin to receptors

- unclear
- may involve establishment of concentration gradient away from primary site of action of LA

Physiological effects

- Reduces hepatotoxicity
- mucolytic

—

- energy substrate (essential fatty acids)
- managing lipophilic drug overdose by binding and facilitating clearance

Absorption

PO: BA low

-

IV only

Protein binding

66-97%
Albumin

-

None

Volume of distribution

0.5 L/kg

0.3 L/kg [DigiFab]
0.4 L/kg [Digibind]

Wide - distributed to fat and tissues

Metabolism

Liver
Deacetylated to cysteine -> normal metabolism (Rapid)

Nil

Liver
Broken down to Fatty acids and glycerol

Excretion

Unchanged: 40% urine, 3% feces

Urine

Liver and kidneys

Half-life

5.5 hrs

Unbound: 11 hrs
Bound: 15-20 hrs

not well defined

Adverse Effects Toxicity

usually in 1st hr:
- rash around infusion site
- angiooedema
- bronchospasm
- hypo/hyper tension

Mx: stop, give antihistamine, then restart at slowest infusion rate

Anaphylaxis – rare
Digoxin Withdrawal: AF, heart failure, hypokalemia

- Fat embolism
- Hyperlipidemia, pancreatitis
- Hepatic dysfunction
- Allergic reactions

Chemical Pharmaceutics

Synthetic derivative of cysteine

Monoclonal antibody (mAB) FAB (Fragment antigen-binding) fragment from sheep immunized with digoxin derivative

fat emulsion

Class Group

Antidote

Antidote

Antidote


Antidotes · Antidotes

Antidotes

Indications Uses

- paracetamol overdose
- non-paracetamol induced fulminant hepatic failure
- prevention of contrast nephropathy
- mucolytic therapy

- For treatment of acute and chronic digoxin overdose
- Treatment of toxicities of other cardiac glycosides: oleander, bufotoxin (cane toad), Chinese medicines

- TPN mixtures
- Local anaesthetic toxicity with or without circulatory arrest
- Prevention of essential fatty acid deficiency syndrome

Legacy Cicm Level

Level 3

Level 3

Level 3

Main Action

antioxidant and glutathione inducer

Binds Digoxin Molecules

- Energy substrate
- Reverse local anaesthetic cardiotoxicity

Onset Peak Duration

Duration: short

Onset: 0-60min
Peak: 30-360min

(For LA tox)
onset: minutes
peak: 15-30mins

Presentation

IV or oral formulation
200mg/mL
compatible with 5% dextrose

powder
contains 38-40mg of digoxin-specific Fab fragments (which binds approx. 0.5mg Digoxin)
reconstitute with sterile water

white, oil-water emulsion with 20% soybean oil, egg yolk phospholipids, glycerin, sodium hydroxide and water

Route And Dose

IV, PO, Neb (inhaled)

IV:
1st : 150mg/kg in 200ml dextrose over 15mins
2nd : 50mg/kg in 500ml over 4hrs
3rd : 100mg/kg in 1l over 16hrs

IV

Empiric: 10vials of Fab fragments

Known dose, no level:
Total body load = Dose (in mg) x 0.8 (BA of digoxin)
Number of vials = TBL x 2

Known concentration:
No of vials = [(serum digoxin concentration in ng/mL) x (patient's weight in kg)]/ 100

IV

For LA tox: 1.5ml/kg bolus over 1 minute →
Infusion 15 ml/kg/hr

If not stabilized, two subsequent boluses may be given 5 mins apark.
Then rate doubled to 30ml/kg/hr

Max cumulative dose 12ml/kg

Special Points — —

serum amylase or lipase should be monitored for
2 days