NEODOSE

INDICATIONS

• Acetaminophen Overdose: For specific treatment management call 1-800-222-1222 (regional poison center) or 1-800-525-6115 (special health professional assistance line). Management of acetaminophen overdose is based on adult and some pediatric data with most of pediatric management extrapolated from adult data. The Rumack-Matthew nomogram (based on adult data) stratifies the risk of hepatoxicity based on acetaminophen concentrations at a specified time after a single acute acetaminophen ingestion (4 to 24 hours post ingestion); however, the nomogram may not be appropriate to utilize in the neonate population. In adults, patients with acetaminophen concentrations within the possible or probable toxic range would warrant acetylcysteine treatment. The ideal time of acetylcysteine administration is within 8 to 10 hours postingestion. The nomograph can not be used with other types of ingestions (greater than 24 hours after presentation, an unknown time or duration of ingestion, extended-release preparation ingestion, or a repeated supra-therapeutic ingestion). Although weaker evidence exist, acetylcysteine can be administered to patients with hepatic failure presumably due to acetaminophen, to patients who have hepatotoxicity thought to be due to acetaminophen, and to patients who have a suspected or known acetaminophen overdose, including repeated supra-therapeutic ingestions. The Rumack-Matthew nomogram, which was developed using data from oral overdoses, may not be appropriate when acetaminophen overdose is received by the IV route. Under these circumstances, acetylcysteine should be considered after a single IV dose above 60 mg/kg. Data in neonates treated with acetylcysteine are limited to case reports with ages ranging from 1 day of age (3.78 kg) to 22 days of age (4.1 kg), including preterm neonates as young as postmenstrual age 27.3 weeks (12 days of age; weight 940 grams) . All neonates experienced full recovery with most experiencing no evidence of liver toxicity during and after the course of acetylcysteine treatment. Although neonates may not be as susceptible to liver injury compared to children or adults due to differences in hepatic development, acetylcysteine is the standard treatment.
• Gastric Lactobezoar: A gastric lactobezoar was successfully treated after 4 doses of acetylcysteine 10 mg/kg/dose via nasogastric (NG) tube every 6 hours in a 1 month of age full-term infant. Each dose was diluted in 50 mL of normal saline and administered over 30 minutes, then the NG tube was clamped for 2 hours, followed by aspiration at 3 and 6 hours after the dose.
• Lung Disease, Non-Cystic Fibrosis: Evidence is limited and does not support the use of oral or inhaled acetylcysteine for non-cystic fibrosis lung disease such as primary ciliary dyskinesia, chronic lung disease of infancy, pneumonia, asthma, atelectasis, inhalation injury, or lower respiratory tract infection in pediatric patients or neonates. A 6-day course of I acetylcysteine (16 to 32 mg/kg/day) started before the age of 36 hours did not improv mortality, the incidence of bronchopulmonary dysplasia, or lung function in a randomized double-blind, placebo-control trial (n=391; weight range 500 to 999 g). Furthermore harm was demonstrated in 10 ventilated premature infants with chronic lung disease an treated with intratracheally administered acetylcysteine for 7 days

FDA APPROVED INDICATION

• Inhalation Solution:Indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in several conditions, including:
  • Acute bronchopulmonary disease
  • Atelectasis due to mucous obstruction
  • Chronic asthmatic bronchitis
  • Chronic respiratory disease
  • Diagnostic bronchial studies
  • Post-traumatic chest conditions
  • Pulmonary complications of cystic fibrosis
  • Respiratory complication of surgical procedure
  • Tracheostomy care
  • Use during anesthesia
• Oral/IV Solution: Indicated as an antidote to prevent or lessen hepatic injury that may occur following the ingestion of a potentially hepatotoxic quantity of acetaminophen in patients with acute ingestion or from repeated supratherapeutic ingestion.
• Inhalation Solution:Effervescent Tablets: Indicated as an antidote to prevent or lessen hepatic injury that may occur following the ingestion of a potentially hepatotoxic quantity of acetaminophen in patients with acute ingestion or repeated supra-therapeutic ingestion (exposure to higher than recommended dosages for extended periods of time).

CONTRAINDICATIONS/PRECAUTIONS

• Inhalation solution: Liquefied bronchial secretions may increase in volume, leading to airway obstruction if cough is inadequate; mechanical suction may be required. Bronchospasm may occur in asthmatics. As increased concentration of drug may occur from solvent evaporation, dilution of nebulizing solution with appropriate amounts of sterile water for injection is recommended
• IV solution: Acute flushing and erythema may develop, usually within 30 to 60 minutes after initiating therapy and usually will spontaneously resolve. However, serious acute hypersensitivity reactions, including fatal cases, have been reported. Use with caution in patients with asthma due to risk of bronchospasm. In patients less than 40 kg and for those requiring fluid restriction, fluid overload potentially leading to hyponatremia, seizure, and death may occur; therefore, diluent volume needs to be adjusted.
• Oral solution: If encephalopathy due to hepatic failure occurs, discontinue treatment to avoid further exposure to nitrogenous substances. Evaluate risk versus benefit in patients at risk of gastric hemorrhage (eg, esophageal varices, peptic ulcer) due to increased vomiting with treatment.

ADVERSE EFFECTS

IV infusion of acetylcysteine did not produce adverse effects in one study of preterm newborns (n=10; gestational age, 25 to 31 weeks; weight, 500 to 1380 g) when administered at a mean rate of 4.2 mg/kg/hr for 24 hours, or in a second study of newborns (n=6; gestational age, 26 to 30 weeks; weight, 520 to 1335 g) when administered at a rate of 0.1 to 1.3 mg/kg/hr for 6 days. Hypernatremia developed in a preterm infant (30 weeks gestation) administered oral acetylcysteine solution (33.5 mmol/kg/day sodium from acetylcysteine) for meconium ileus. Sodium concentration returned to normal after acetylcysteine was discontinued.

ADMINISTRATION

• Effervescent Tablet: Dissolve two 2.5-gram tablets in 100 mL of water for a 50 mg/mL solution Administer immediately or within 2 hours of preparation once tablets are dissolved. If vomiting occurs within 1 hour of administration, repeat dose. May be administered by nasoduodenal tube
• Oral Solution: Dilute the 20% solution with diet cola or other diet soft drink to a final concentration of 5% (add 3 mL of diluent for each 1 mL of 20% solution; do not decrease the proportion of diluent). If administered via gastric tube or Miller-Abbott tube, water may be used as the diluent. Administer within 1 hour of dilution. Repeat dose if patient vomits within 1 hour of administration. Dilution may minimize vomiting. May be administered by duodenal intubation if persistent vomiting is present. Not for parenteral injection. If activated charcoal has been administered, then gastric lavage must be performed before administration of oral acetylcysteine
• IV Solution: Acetadote® is hyperosmolar (2600 milliosmoles/liter [mOsmol/L]) and the osmolarity of the solution is increased as the diluent volume is decreased; adjust osmolarity to physiologically safe level, generally not less than 150 mOsmol/L in children.Concentration of vial is 200 mg/mL. See Dose Section for rate and infusion concentration.

MONITORING

• Inhalation Therapy: Monitor patients with asthma closely during inhalation therapy. Monitor renal and hepatic function and electrolytes throughout therapy.
• IV/Oral Therapy for Overdose: Obtain plasma or serum acetaminophen levels prior to detoxification. For acute ingestion, obtain as early as possible but no sooner than 4 hours postingestion. If extended-release acetaminophen was ingested and the acetaminophen concentration at 4 hours post ingestion was below the possible toxicity line, draw a second sample at 8 to 10 hours post ingestion. Assess hepatic function (AST, ALT, bilirubin, INR, prothrombin time), renal function (creatinine and BUN), blood glucose, and electrolytes prior to detoxification, and throughout treatment. Assess acetaminophen levels as needed during treatment to determine need for continued therapy. Assess acetaminophen levels, ALT/AST, and INR after the last maintenance dose. Carefully monitor patients with asthma or with a history of bronchospasm during initiation and throughout therapy.