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ACETYLCYSTEINE DOSING INFORMATION 1.4 PEDIATRIC DOSAGE 1.4.1 NORMAL DOSE A. ORAL 1. ACETAMINOPHEN POISONING a. The acute ingestion of acetaminophen in quantities of 150 milligrams/kilogram or greater may result in hepatic toxicity. Acetylcysteine is most effective in preventing acetaminophen-induced liver injury following overdose if administered within 16 hours postingestion. Loading dose is 140 milligrams/kilogram orally followed by 70 milligrams/kilogram orally every 4 hours for 17 additional doses (Peterson & Rumack, 1977; Peterson & Rumack, 1978). b. The manufacturer recommends that regardless of the quantity of acetaminophen reported to have been ingested, acetylcysteine should be administered if 24 hours or less have elapsed from the time of the reported ingestion of an overdose. Do not wait for the result of laboratory assays for acetaminophen levels. The following procedures are recommended (Prod Info Mucomyst(R), 1996): (1) The stomach should be emptied by lavage or emesis with syrup of ipecac. Syrup of ipecac should be given in a dose of 15 to 30 milliliters for children and 30 to 40 milliliters for adults accompanied by 4 to 6 ounces of water. The dose should be repeated if emesis does not occur in 20 minutes. (2) In the cases of a mixed drug overdose, activated charcoal may be indicated. If activated charcoal is administered, it is recommended that the patient be lavaged before administration of acetylcysteine since activated charcoal adsorbs acetylcysteine in vitro and may also do so in vivo. (3) Blood should be drawn for acetaminophen plasma assay and for baseline SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar, and electrolytes. Plasma or serum acetaminophen concentrations should be determined as early as possible but no sooner than 4 hours following acute overdose. These levels are essential in assessing the potential risk of hepatotoxicity. If an assay for acetaminophen cannot be obtained, it is necessary to assume the overdose is potentially toxic. (4) Administer the loading dose of acetylcysteine (140 milligrams/kilogram of body weight). (5) Four hours after the loading dose, administer the first maintenance dose of 70 milligrams/kilogram. Maintenance doses should be repeated at 4-hour intervals for a total of 17 doses unless the initial acetaminophen assay reveals a nontoxic level. (6) If the patient vomits the loading dose or any maintenance dose within 1 hour of administration, repeat that dose. If the patient is persistently unable to retain the acetylcysteine, it may be administered by duodenal intubation. (7) Repeat SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar, and electrolytes daily if the acetaminophen plasma level is in the potentially toxic range. 2. MUCOLYTIC a. Children 6 to 14 years, 300 to 400 mg daily in 3 to 4 divided doses; and children 2 to 5 years of age, 200 to 300 mg daily in 2 to 3 divided doses (Fachinfo Fluimucil(R) akut, 1997). B. ORAL SOLUTION PREPARATION 1. The 20% acetylcysteine solution should be diluted with cola drinks, Fresca, or other soft drinks to a final concentration of 5%. If administered via gastric tube or Miller-Abbott tube, water may be used as the diluent. The dilution should be freshly prepared and utilized within one hour. C. ORAL DOSAGE GUIDE AND PREPARATION 1. Doses of oral acetylcysteine in relation to body weight are (Prod Info Mucomyst(R), 1996): LOADING DOSE** Weight Acet- Muco- Dilu- Total (kg) ylcys- myst ent 5% sol- teine 20% (mL) ution (g) (mL) (mL) --------------------------------------- 100-109 15 75 225 300 90-99 14 70 210 280 80-89 13 65 195 260 70-79 11 55 165 220 60-69 10 50 150 200 50-59 8 40 120 160 40-49 7 35 105 140 30-39 6 30 90 120 20-29 4 20 60 80 MAINTENANCE DOSE** Weight Acet- Muco- Dilu- Total (kg) ylcys- myst ent 5% sol- teine 20% (mL) ution (g) (mL) (mL) --------------------------------------- 100-109 7.5 37 113 150 90-99 7 35 105 140 80-89 6.5 33 97 130 70-79 5.5 28 82 110 60-69 5 25 75 100 50-59 4 20 60 80 40-49 3.5 18 52 70 30-39 3 15 45 60 20-29 2 10 30 40 **If patient weighs less than 20 kg (usually patients younger than 6 years), calculate the dose of Mucomyst(R). Each milliliter of 20% Mycomyst(R) contains 200 milligrams of acetylcysteine. The loading dose is 140 milligrams/kilogram. The maintenance dose is 70 milligrams/kilogram. Three (3) milliliters of diluent are added to each milliliter of 20% Mucomyst(R). Do not decrease the proportion of diluent. D. INTERPRETATION OF ACETAMINOPHEN ASSAY 1. When results of the plasma acetaminophen assay are available, the Rumack/Matthew nomogram (available in Mucomyst(R) package inserts) should be utilized to determine if plasma concentrations are in the potentially toxic range. Values above the solid line connecting 200 micrograms/milliliter at 4 hours with 50 micrograms/milliliter at 12 hours are associated with a possibility of hepatic toxicity if acetylcysteine is not administered. If the plasma level is above the broken line on the nomogram, continue with maintenance doses of acetylcysteine. If the initial plasma level is below the broken line on the nomogram, there is minimal risk of hepatic toxicity and acetylcysteine treatment can be discontinued (Prod Info Mucomyst(R), 1996). E. INTRAVENOUS 1. ACETAMINOPHEN POISONING a. SUMMARY (1) There is NO FDA-approved commercially available sterile, pyrogen-free, intravenous (IV) formulation of acetylcysteine in the United States. The oral/inhalation preparation is NOT officially approved for IV use. Pyrogen-free intravenous acetylcysteine is available investigationally ONLY through participating poison centers. There are 2 intravenous protocols currently under investigation. (2) FORTY-EIGHT HOUR PROTOCOL: Dilute 20% solution 1:5 in dextrose 5% in water (D5W) and give slowly over one hour. If an adverse reaction occurs, diphenhydramine is given and subsequent doses are given over 2 hours. The initial dose is 140 milligrams/kilogram, followed by 70 milligrams/kilogram every 4 hours for a total of 13 doses (Smilkstein et al, 1991). (3) TWENTY HOUR PROTOCOL: Administer 150 milligrams/kilogram in 200 milliliters D5W over 15 minutes, followed by 50 milligrams/kilogram in 500 milliliters D5W over 4 hours, followed by 100 milligrams/kilogram in 1 liter D5W over the next 16 hours (Prescott et al, 1979; Westman, 1989). (4) There does appear to be a slight increased risk of adverse reactions following intravenous administration (primarily urticaria and/or bronchospasm which are rate-related, but anaphylactoid reactions have occurred). b. Intravenous acetylcysteine is safe and effective for preventing the hepatic and renal toxicities following overdose of acetaminophen (Prescott, 1981). Similar findings were reported elsewhere (Shenfeld & Oh, 1980). c. Dosing information is as follows (Westman, 1989): Patients who present with toxic levels of acetaminophen less than 10 hours after ingestion should receive acetylcysteine intravenously for 20 hours (150 milligrams/kilogram of body weight as a bolus dose, followed by 50 milligrams/kilogram for 4 hours and then 100 milligrams/kilogram for 16 hours). Patients who present with toxic levels of acetaminophen more than 10 hours after ingestion should receive acetylcysteine IV for 48 hours (150 milligrams/kilogram as a bolus dose, followed by 50 milligrams/kilogram for 4 hours and then 286 milligrams/kilogram for 44 hours). Hemoperfusion may be of value and should be considered for patients presenting early with toxic levels of acetaminophen and severe acidosis, presenting early with extremely high levels of acetaminophen (4000 nmol/liter or more) and patients presenting more than 15 hours after the ingestion with serum levels exceeding 1000 nmol/liter. F. INTRAVENOUS RATE OF ADMINISTRATION 1. Adverse reactions to intravenous acetylcysteine appear to be rate- dependent. Intravenous acetylcysteine should be administered slowly over 1 hour; however if an adverse reaction occurs, diphenhydramine is given and subsequent doses are given over 2 hours to minimize complications (Smilkstein et al, 1991; Tenenbein, 1984). G. RECTAL 1. ACETAMINOPHEN POISONING a. There are no reports of acetylcysteine being administered rectally for treatment of acetaminophen poisoning. The extent of its absorption via the rectum is not known (Pers Comm, 1983; Pers Comm, 1983a). Rectal administration of acetylcysteine solution is not recommended for treatment of acetaminophen overdose. For patients not able to retain oral doses of acetylcysteine, administration of diluted doses via nasogastric tube or by slow intravenous infusion may be tried. An intravenous formulation of acetylcysteine is available in the United States under an investigational protocol through participating poison centers. 2. MECONIUM ILEUS a. Acetylcysteine enemas together with acetylcysteine orally have been used with apparent success in neonates, children, and adults with bowel obstruction due to meconium ileus or meconium ileus equivalent. A 4% to 6% acetylcysteine enema (diluted in 100 to 300 milliliters of water or normal saline) administered every 6 to 12 hours appears to be effective and safe, but higher concentrations have been used (Spiro, 1977; Hodson et al, 1976; Derman et al, 1975; Shaw, 1969; Simpson et al, 1968). H. RESPIRATORY ADMINISTRATION 1. PULMONARY DISORDERS a. Acetylcysteine has been administered via tracheostomy, intratracheal catheter, nebulizer, intermittent positive pressure breathing (IPPB), endotracheal tube and cannula (Webb, 1962). It is generally felt that direct instillation or intermittent positive pressure breathing (IPPB) are much superior to nebulization (Poppe, 1964; Miller, 1973). When administered by direct instillation, 1 to 2 milliliters of a 10% to 20% solution may be given as often as every hour. When used for the routine care of patients with tracheostomy, 1 to 2 milliliters of a 10% to 20% solution may be administered every 1 to 4 hours by instillation into the tracheostomy (Prod Info Mucomyst(R), 1996). A dosage of 2 to 5 milliliters of the 10% solution is as effective and produces less bronchoconstriction than higher (20%) concentrations (Hirsch & Kory, 1967). b. When nebulized into a face mask, mouth piece, or tracheostomy, 1 to 10 milliliters of the 20% solution or 2 to 20 milliliters of the 10% solution may be given every 2 to 6 hours. The recommended dose for most patients is 3 to 5 milliliters of the 20% solution or 6 to 10 milliliters of the 10% solution 3 to 4 times daily (Prod Info Mucomyst(R), 1996). c. The 20% solution may be diluted to a lesser concentration with either sodium chloride for injection, sodium chloride for inhalation, sterile water for injection, or sterile water for inhalation. The 10% solution may be used undiluted. Any unused portion of the solution should be stored in the refrigerator and used within 96 hours (Prod Info Mucomyst(R), 1996). d. For treatment of pulmonary complications of surgery or posttraumatic chest conditions, 1 to 2 milliliters of 20% acetylcysteine solution or 2 to 4 milliliters of 10% solution may be given every 1 to 4 hours via a syringe attached to the intratracheal catheter; 2 to 5 milliliters of the 20% solution may be introduced with a syringe through a tracheal catheter when contact with a particular segment of the bronchopulmonary tree is desired (Prod Info Mucomyst(R), 1996; AHFS, 1989).
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