acetylcysteine (Antidote) (Acetadote, Cetylev, N-acetylcysteine (Antidote))

Dosing and uses of Acetadote, Cetylev (acetylcysteine (Antidote))

• Adult
• Pediatric

 

Dosing Forms and Strengths

injectable solution

• 20% (200mg/mL)

effervescent tablets for oral solution (Cetylev)

• 500mg
• 2.5g

 

Acetaminophen Overdose

May administer injectable orally

Continuous IV infusion recommended for acute ingestion (ideally within 8-10 hr following ingestion, but may administer if >10 hr)

Intermittent IV infusion may be considered for late presenting or chronic ingestion (more than 10 hr after ingestion)

Oral administration

• May administer injectable orally
• Loading dose: 140 mg/kg PO
• Maintenance dose: 4 hr after loading dose, start 70 mg/kg PO q4hr for a total 17 doses; repeat dose if emesis occurs within 1 hr of administration

IV continuous infusion

• Acute ingestion (within 8-10 hr after ingestion)
• Administer as 3 doses
• Loading dose: 150 mg/kg IV; mix in 200 mL of D5W and infuse over 1 hr
• Dose 2: 50 mg/kg IV in 500 mL D5W over 4 hr, THEN
• Dose 3: 100 mg/kg IV in 1000 mL D5W over 16 hr
• >100 kg: No specific studies have conducted; limited data suggest a loading dose of 15,000 mg infused IV over 1 hr, then a first maintenance dose of 5,000 mg IV over 4 hr and a second maintenance dose of 10,000 mg over 16 hr

Intermittent IV administration (Off-label)

• Total treatment time 48 hr
• Late presenting or chronic ingestion (>10 hr after ingestion) in patients >40 kg
• Loading dose: 140 mg/kg IV infused over 1 hr (dilute in 500 mL D5W), THEN
• Maintenance dose: 70 mg/kg IV q4h for at least 12 doses (dilute each dose in 250 mL of D5W and infuse over minimum 1 hr)
• Heard K, et al. Clinical Toxicology. 2014 Jun;52(5):512-8. Rocky Mountain Poison and Drug Center

 

Acetaminophen Overdose (Orphan)

Effervescent tablets for oral solution

Orphan designation to prevent hepatic injury from acetaminophen overdose

Sponsor

• Arbor Pharmaceuticals, LLC; 980 Hammond Drive, Bldg Two, suite 1250; Atlanta, GA 30328

 

Other Indications and Uses

Delayed presentation of acetaminophen-induced hepatic failure

 

Pediatric dosage forms and strengths

injectable solution

• 200mg/mL

effervescent tablets for oral solution (Cetylev)

• 500mg
• 2.5g

 

Acetaminophen Overdose

May administer injectable orally

Continuous IV infusion recommended for acute ingestion (ideally within 8-10 hr following ingestion, but may administer if >10 hr)

Intermittent IV infusion may be considered for late presenting or chronic ingestion (>10 hr after ingestion)

Oral administration (Cetylev)

• Loading dose: 140 mg/kg PO
• Maintenance dose: 4 hr after loading dose, give 70 mg/kg PO q4hr for a total of 17 doses; repeat dose if emesis occurs within 1 hr of administration

IV continuous infusion (Acetadote) weight ≤20 kg

• Loading Dose: 150 mg/kg  IV in 3 mL diluent/kg body-weight over 1 hr
• Dose 2: 50 mg/kg IV in 7 mL diluent/kg body-weight over 4 hr
• Dose 3: 100 mg/kg in 14 mL diluent/kg body-weight over 16 hr

IV continuous infusion (Acetadote) >20 kg to <40 kg

• Loading Dose: 150 mg/kg IV in 100 mL of diluent administered over 1hr
• Dose 2: 50 mg/kg IV in 250 mL of diluent administered over 4 hr
• Dose 3: 100 mg/kg IV in 500 mL of diluent administered over 16 hr

IV continuous infusion (Acetadote) weight ≥40 kg

• As adults
• Loading dose: 150 mg/kg IV; mix in 200 mL of D5W and infuse over 1 hr
• Dose 2: 50 mg/kg IV in 500 mL D5W over 4 hr, THEN
• Dose 3: 100 mg/kg IV in 1000 mL D5W over 16 hr

Intermittent infusion (Off-label)

• Total treatment time 48 hr
• Late presenting or chronic (more than 10 hr after ingestion) in patients >40 kg
• Loading dose: 140 mg/kg IV infused over 1 hr (dilute in 200 mL D5W), THEN
• Maintenance dose: 70 mg/kg IV q4h for at least 12 doses (dilute each dose in 250 mL of D5W and infuse over minimum 1 hr)
• Heard K, et al. Clinical Toxicology. 2014 Jun;52(5):512-8. Rocky Mountain Poison and Drug Center

 

Acetadote, Cetylev (acetylcysteine (Antidote)) adverse (side) effects

Frequency not defined

Oral Administration

• Nausea
• Vomiting
• Drowsiness
• Chills
• Fever

IV Administration

• Anaphylactoid reaction due to pyrogens
• Flushing
• Edema
• Urticaria
• Pruritus
• Nausea
• Pharyngitis
• Rhinorrhea

 

Warnings

Contraindications

Hypersensitivity

 

Cautions

Obtain serum acetaminophen concentration at least 4 hr postingestion to determine if toxic levels present before treatment or whether full course necessary

IV used if persistent vomiting precludes PO administration in 1st 8 hr

Consult local regional PCC or medical toxicologist for assistance

IV may cause severe anaphylactic reactions, however, new 2011 IV formulation (replaces the original 2004 IV formulation) does not contain ethylene diamine tetracetic acid or any other stabilization and chelating agents and is free of preservatives

Serious acute hypersensitivity reactions during acetylcysteine administration including rash, hypotension, wheezing, and/or shortness of breath reported in patients receiving intravenous acetylcysteine for acetaminophen overdose; occurred soon after initiation

Total volume administered should be adjusted for patients <40 kg and for those requiring fluid restriction; to avoid fluid overload, volume of diluent should be reduced as needed; if volume not adjusted fluid overload can occur, potentially resulting in hyponatremia, seizure and death

 

Pregnancy and lactation

Pregnancy category: B

Delaying treatment in pregnant women with acetaminophen overdose and potentially toxic acetaminophen plasma levels may increase risk of maternal and fetal morbidity and mortality

Lactation: Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and potential adverse effects on the breastfed child from therapy or from underlying maternal condition

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Acetadote, Cetylev (acetylcysteine (Antidote))

Mechanism of action

Acts as sulfhydryl group donor to restore liver glutathione; may also scavenge free radicals to prevent delayed hepatotoxicity as antioxidant; encourages sulfation pathway of metabolism for acetaminophen

Might be useful against free radicals or reactive metabolites formed by chloroform, carbon tetrachloride, 1,2-dichloropropane, acrylonitrite, doxyrubicin and cyclophosphamide

 

Administration

Instructions

May pretreat with diphenhydramine, hydrocortisone, cimetidine

Should be given within 8 hr of acetaminophen ingestion for maximum benefit; however effective even after 24 hr of ingestion

Acetadote is hyperosmolar (2600 mOsm/L) and is compatible with 5% dextrose (D5W), 0.45% NaCl injection, and sterile water for injection

Decrease total IV volume for patients who weigh <40 kg or if fluid restriction is required

See adult and pediatric dosing for detailed information on oral, intermittent IV infusion, or continuous IV infusion