ACETYLCYSTEINE
  • ACETYLCYSTEINE

  • (Generic for ACETADOTE)
  • QTY 30 • 200 MG/ML • VIAL • Near 77381

ACETYLCYSTEINE (a se teel SIS teen) is a drug that loosens and thins mucus in the lungs. It is used to make breathing easier in patients with bronchitis, cystic fibrosis, emphysema, tuberculosis, or other lung problems.

ACETYLCYSTEINE Pediatric Monographs
  • General Administration Information
    For storage information, see specific product information within the How Supplied section.

    Route-Specific Administration

    Oral Administration
    Oral Liquid Formulations
    Oral solution (Mucomyst):
    -Oral acetylcysteine has very poor taste and a strong sulfur-like odor. Diluting the solution with a very cold beverage (e.g., soda, orange juice), serving in a cup with a lid, and drinking the solution through a straw may help to increase palatability and lower the risk of vomiting.-Dilution of 10% solution: 1 ml of diluent for every 1 ml of solution.
    -Dilution of 20% solution: 3 ml of diluent for every 1 ml of solution.

    -If the patient cannot drink, the solution may be administered via a nasogastric tube.
    -Use diluted solutions within 1 hour of preparation.
    -If the patient vomits within 1 hour of administration, repeat dose.
    -Storage: Remaining undiluted solutions in opened vials can be stored in the refrigerator up to 96 hours.

    Effervescent tablet for oral solution (Cetylev):
    -For oral administration only; DO NOT administer via parenteral injection, nebulizer, or intratracheal instillation. Administration via a nasoduodenal tube may be considered for patients persistently unable to tolerate the orally administered dose.
    -Prepare only one dose at a time; each freshly prepared dose must be used within 2 hours.
    -Adults and pediatric patients weighing 20 kg or more: Use the patients weight and manufacturer provided dosing charts to calculate the number of 2.5 gram and 500 mg effervescent tablets required to make the 140 mg/kg loading dose and the 70 mg/kg maintenance doses.-Patients weighing 60 kg or more: Dissolve the required number of tablets in 300 mL of water. Note, data are limited regarding dosing requirements for patients weighing over 100 kg.
    -Patients weighing 20 to 59 kg: Dissolve the required number of tablets in 150 mL of water.

    -Pediatric patients weighing 19 kg or less: Dissolve two 2.5 gram tablets in 100 mL of water to create a 50 mg/mL solution. -Calculate the loading dose volume (mL): multiply patients weight (kg) by 140 mg/kg, then divide by 50 mg/mL (solution concentration).
    -Calculate the maintenance dose volume (mL): multiply patients weight (kg) by 70 mg/kg, then divide by 50 mg/mL (solution concentration).

    -Once tablets have dissolved in the required volume of water, administer solution immediately. If the patient vomits within 1 hour of oral administration, repeat that dose.
    -The solution produced by the effervescent tablets is interchangable with the 20% acetylcysteine solution, provided the effervescent tablet solution was appropriately prepared and diluted, and if the same acetylcysteine dosage is given.



    Injectable Administration
    -Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
    -The color of the IV formulation may turn from colorless to a slight pink or purple color after the stopper is punctured; however, the quality of the product is not affected.
    Intravenous Administration
    Dilution
    -The IV formulation is hyperosmolar (2600 mOsm/L) and must be diluted prior to administration.
    -Compatible diluents include: 5% Dextrose, 0.45% NaCl, and Sterile Water for Injection. If Sterile Water for Injection is used, carefully consider the osmolarity of the resultant solution; some concentrations would be too hypo-osmolar for safe administration (see osmolarity content below).
    -The standard volume of diluent to be used is dependent on patient weight as follows:- Patients weighing 5-20 kg:-Loading dose: dilute in 3 ml/kg diluent
    -Second dose: dilute in 7 ml/kg diluent
    -Third dose: dilute in 14 ml/kg diluent

    -Patients weighing 21-40 kg:-Loading dose: dilute in 100 ml diluent
    -Second dose: dilute in 250 ml diluent
    -Third dose: dilute in 500 ml diluent

    -Patients weighing >= 41 kg:-Loading dose: dilute in 200 ml diluent
    -Second dose: dilute in 500 ml diluent
    -Third dose: dilute in 1000 ml diluent


    -For patients requiring fluid restriction, the volume of dilution should be reduced as clinically appropriate; however, carefully consider the osmolarity of the resultant solution and avoid infusion of a hyper- or hypo-osmolar solution.-Acetylcysteine diluted to a concentration of 7 mg/ml-Osmolarity in 0.45% NaCl: 245 mOsmol/L
    -Osmolarity in 5% dextrose (D5W): 343 mOsmol/L
    -Osmolarity in Sterile Water for Injection: 91 mOsmol/L (below recommended osmolarity for administration)

    -Acetylcysteine diluted to a concentration of 24 mg/ml-Osmolarity in 0.45% NaCl: 466 mOsmol/L
    -Osmolarity in 5% dextrose (D5W): 564 mOsmol/L
    -Osmolarity in Sterile Water for Injection: 312 mOsmol/L


    -The manufacturer provides a Dosage Guide and Preparation Chart in relation to body weight in the product label.
    -Storage: The commercially available vials are intended for single-dose use and are preservative-free. Diluted solutions are stable for 24 hours at controlled room temperature.

    IV Infusion
    -Administer the 3 portions of the regimen sequentially as a continuous infusion with no significant time between doses (total infusion time is about 21 hours). The recommended infusion times for each dose are as follows:-Loading dose: infuse over 1 hour
    -Second dose: infuse over 4 hours
    -Third dose: infuse over 16 hours

    -Infusions beyond 21 hours can be considered in certain clinical situations. If the infusion is extended beyond 21 hours, the treating physician should contact either the US poison center (1-800-222-1222) or a special health professional assistance line for APAP overdose (1-800-525-6115) for assistance with dosing recommendations.
    -Acetylcysteine reacts with certain materials (e.g., iron, nickel, copper, rubber); any part of the IV equipment that comes in contact with acetylcysteine should be made of plastic or glass.



    Inhalation Administration
    -Solutions may be given via nebulization into a face mask, mouth piece, tracheostomy, tent, or croupette; direct instillation intratracheally is also FDA-approved.
    -The 10% solution may be administered undiluted.
    -The 20% solution may be administered undiluted or, if desired, may be diluted in 0.9% NaCl or Sterile Water for Injection or Inhalation.
    -Most commercially available nebulizers will produce appropriate particle sizes; however, hand bulbs and some hand-operated nebulizers are not recommended for routine use nebulizing acetylcysteine.
    -Do not place acetylcysteine directly into the chamber of a heated nebulizer.
    -For prolonged nebulizations, when 3/4 of the initial volume of acetylcysteine has been nebulized, a quantity of Sterile Water for Injection approximately equal to the remaining acetylcysteine volume should be added to the nebulizer.
    -Acetylcysteine reacts with certain materials (e.g., iron, nickel, copper, rubber); therefore, any part of the nebulizer equipment that comes in contact with acetylcysteine should be made of plastic or glass.
    -Storage: Opened vials may be stored in the refrigerator and used within 96 hours.


    Other Administration Route(s)
    Intratracheal Administration
    -Intratracheal instillation: Instill directly into the trachea or tracheostomy.
    -Percutaneous intratracheal catheter: Administer the solution via a syringe attached to the catheter.

    The overall incidence of adverse reactions to intravenous acetylcysteine has been reported to be between 0.2% and 20.8%; adverse reactions most commonly occur during the loading dose infusion.

    Serious anaphylactoid reactions have occurred in patients who have received intravenous acetylcysteine; medications used to treat anaphylaxis must be readily available during administration. In a pediatric trial (n = 1905), the overall incidence of anaphylactoid reactions was 9.5%, 0.2% of patients experienced anaphylaxis, and 0.1% experienced hypotension. In adult trials, 14% of patients developed an anaphylactoid reaction during the first 2 hours of therapy when the loading dose was infused over 60 minutes compared to 18% when it was infused over 15 minutes. Acute flushing and erythema may also occur with IV acetylcysteine administration; these reactions typically occur 30-60 minutes after the initiation of the infusion and often resolve spontaneously despite continued acetylcysteine infusion. In a trial of 1905 pediatric patients, urticaria/facial flushing occurred in 7.6% of patients and pruritus occurred in 4.1%. If a reaction occurs that includes signs and symptoms more severe than simple flushing and erythema, treat it as an anaphylactoid reaction. Administer appropriate pharmacological therapy (e.g. antihistamines, epinephrine, etc.) and supportive care as needed. The acetylcysteine infusion may be interrupted until treatment for the reaction has been initiated and then carefully reinitiated once the patient is stable. If the anaphylactoid reaction occurs again, the infusion should be discontinued and alternative treatment measures considered. Although serious hypersensitivity reactions are most commonly associated with the intravenous formulation, generalized urticaria and rash (unspecified) have also been observed rarely after oral acetylcysteine therapy. Acquired sensitization (dermal eruptions) has also been reported with nebulized acetylcysteine.

    Respiratory symptoms (cough, wheezing, stridor, dyspnea, chest tightness, respiratory distress, or acute bronchospasm) occurred in 2.2% of pediatric patients in one clinical trial of intravenous acetylcysteine (n = 1905). Bronchospasm can also occur with orally administered acetylcysteine, although the incidence is infrequent. Nebulized acetylcysteine may irritate the airways of patients who are hypersensitive to acetylcysteine or in asthmatic patients. If patients are receiving inhaled beta-agonist treatments, it is often recommended that the beta-agonist be used prior to inhaled acetylcysteine administration to limit bronchospasm. If wheezing or dyspnea occurs during the administration of intravenous acetylcysteine, evaluate the patient carefully to determine whether the wheezing may be a symptom of an anaphylactoid reaction. Use all acetylcysteine formulations cautiously in patients with asthma or a history of bronchospasm. Other respiratory adverse events that have been reported with IV acetylcysteine use include pharyngitis, rhonchi, and throat tightness. Stomatitis has been reported by patients who used the oral/nebulized solution. Hemoptysis has occurred in patients receiving nebulized acetylcysteine; however, hemoptysis is not uncommon in patients with bronchopulmonary disease and a causal relationship has not been established. Rhinorrhea has been reported with both IV and inhaled/oral acetylcysteine.

    All formulations of acetylcysteine have been associated with nausea and vomiting ; however, the oral administration of acetylcysteine solution is particularly known for causing GI symptoms. Acetylcysteine solution for oral administration has a strong, unpleasant sulfuric odor and taste that increase the risk of nausea, vomiting, and dysgeusia. Some investigators have found that diluting the acetylcysteine with beverages such as cold soda reduces the offensiveness of the smell and taste, which may lead to a reduction in nausea and vomiting. Dysgeusia may also be limited during oral administration by using a drinking straw for the diluted solutions and serving it in a cup with a lid. Because acetaminophen toxicity is highly emetogenic, it is difficult to determine the incidence of nausea secondary to acetylcysteine in this setting. In addition, orally administered acetylcysteine can be irritating to the GI mucosa. In patients with esophageal varices or peptic ulcer disease, vomiting may increase the risk of hemorrhage or esophageal tears.

    In a trial of intravenous acetylcysteine in 1905 pediatric patients, 1.2% developed edema; monitor fluid status in all patients during administration. In an adult trial comparing IV loading dose infusion rates, 5% of patients who received the loading dose over 15 minutes and 3% of those who received the dose over 60 minutes experienced tachycardia (e.g. sinus tachycardia) within the first 2 hours after administration. However, in a multi-center study of adults (n = 4709) and pediatric patients (n = 1905) treated with IV acetylcysteine, tachycardia was not reported as an adverse reaction. Chest tightness has been reported with the inhaled/oral acetylcysteine.

    Drowsiness, clamminess, and fever have been reported during oral or inhalational use of acetylcysteine. Drug-induced fever would also be a potential expected side effect of intravenous administration, although this has not been reported by the manufacturer.

    Elevated hepatic enzymes were reported in a case report involving a 3 year old boy with cystic fibrosis receiving acetylcysteine for distal intestinal obstruction syndrome (meconium ileus equivalent). He was hospitalized on 2 different occasions and hepatic enzymes were within normal limits prior to admission, but were grossly elevated after acetylcysteine administration. During the first hospitalization the patient received acetylcysteine 4% solution, 50 ml every 6 hours (14 total doses) and acetylcysteine enemas 4% solution, 150 ml every 6 hours (13 total doses). Four days after beginning acetylcysteine his laboratory values were: SGOT: 4850 IU/L, SGPT 4820 IU/L, and alkaline phosphatase: 495 IU/L. Acetylcysteine and cefaclor were discontinued and a week later the values were: SGOT: 143 IU/L, SGPT: 965 IU/L, and alkaline phosphatase: 867 IU/L. When readmitted 2 months later for meconium ileus equivalent, acetylcysteine enemas were begun, 200 ml of 5% solution given every 4-6 hours (25 total doses). Theophylline and nebulized bronchodilators were the only other medications administered. Five days after admission, hepatic enzymes were again elevated and improved a week after acetylcysteine discontinuation. Four months later, his enzymes were further improved. The patient's liver biopsy was compatible with drug-induced injury, but also showed hepatobiliary lesions that occur with cystic fibrosis.

    Intravenous acetylcysteine is contraindicated in patients who have had a previous anaphylactoid reaction to acetylcysteine, and acetylcysteine solution for oral use or inhalation is contraindicated in patients who have had any type of hypersensitivity reaction to the drug. Serious anaphylactoid reactions, including the death of an asthmatic patient, have been reported in patients who received intravenous acetylcysteine. If a reaction to intravenous acetylcysteine involves more than simple flushing and erythema of the skin, it should be treated as an anaphylactoid reaction. The acetylcysteine infusion may be interrupted until the anaphylactoid reaction treatment has been initiated and symptoms stabilized. The infusion may be carefully restarted, but if the anaphylactoid reaction returns or the severity of symptoms increases, stop the infusion and consider alternative treatment. Agents used in the treatment of anaphylaxis (e.g., IV antihistamines and epinephrine) should be readily available in areas where intravenous acetylcysteine is administered.

    Use intravenous and nebulized acetylcysteine with caution in patients with asthma because both formulations can result in acute bronchospasm. To minimize the risk of bronchospasm, inhaled acetylcysteine should be used with or after the administration of a nebulized bronchodilator. Nebulized acetylcysteine should also be used with caution in patients with respiratory insufficiency, an inadequate cough mechanism, or gag reflex depression. When administered into respiratory tract, either via inhalation or direct administration into a tracheostomy tube, acetylcysteine liquifies pulmonary secretions, and the increased volume produced can occlude the airway if the patient is unable to adequately clear the secretions. If the patient's cough is not adequate to keep the airway open, mechanical suction or endotracheal aspiration may be necessary. Monitor all patients with any respiratory conditions carefully while they are receiving acetylcysteine.

    Use oral acetylcysteine cautiously in patients who are vomiting and those who have pre-existing GI disease. Oral acetylcysteine can cause or exacerbate vomiting and when undiluted, has irritating and sclerosing properties on the GI mucosa. In patients with esophageal varices or peptic ulcer disease, vomiting may increase the risk of hemorrhage or esophageal tears. The acetylcysteine solution has an unpleasant odor that increases the risk of vomiting and may cause some children to refuse to drink it. Diluting oral acetylcysteine with cold soda, administering it in a cup with a lid, and having the patient drink it through a straw may minimize the mask/hide the odor and increase the likelihood of proper administration.

    Use intravenous acetylcysteine cautiously in patients who require fluid restriction, such as patients with heart failure. The usual recommended administration technique for intravenous acetylcysteine (Acetadote) involves a significant amount of fluid and could result in volume overload and even hyponatremia, seizures, and death in extreme cases. For patients requiring fluid restriction, the volume of dilution should be reduced as clinically appropriate; however, carefully consider the osmolarity of the resultant solution and avoid infusion of a hyper- or hypo-osmolar solution. For specific treatment recommendations for patients requiring non-standard administration techniques clinicians can contact the US poison center (1-800-222-1222) or a special health professional assistance line for APAP overdose (1-800-525-6115) for assistance. Caution is advised when administering the acetylcysteine effervescent tablets to patients on a sodium restricted diet (i.e., patients with hypertension, heart failure, renal disease). Each 500 mg and 2.5 gram effervescent tablet contains 3.8 meq and 19 meq of sodium, respectively.

    Description: Acetylcysteine is the N-acetyl derivative of L-cysteine. Although it was originally marketed as a mucolytic, acetylcysteine is commonly used intravenously or orally for acetaminophen (APAP) overdose. In patients with cystic fibrosis, acetylcysteine is also used for management of distal intestinal obstruction syndrome (DIOS), previously known as meconium ileus equivalent. Prophylactic administration of acetylcysteine, along with hydration, aids in the prevention of nephrotoxicity induced by radiographic-contrast agents in high-risk adult patients ; however, data for this indication in pediatric patients are lacking. Acetylcysteine has been studied as a sulfhydryl substrate for regenerating the activity of nitrates after the development of tolerance, but is not widely used for this purpose. The drug continues to be investigated as an antioxidant to ameliorate the toxic effects of ischemic injury on various tissues, including the heart, kidney, liver, and lung. Additionally, it has been studied as a pharmacotherapy for substance dependence and as an adjunctive therapy in patients with autism; however, limited data are available. Because acetylcysteine contains sulfhydryl groups, it possesses a strong odor, often described as smelling like rotten eggs. Acetylcysteine is FDA-approved in pediatric patients with no minimum age specified.

    For the prevention of hepatotoxicity after acute acetaminophen overdose:
    NOTE: The Rumack-Matthew nomogram should be used to estimate the hepatotoxicity potential from an acute acetaminophen (APAP) overdose in patients with a known APAP concentration, a known APAP ingestion time, and who present within 8 hours of the overdose. For patients whose serum APAP concentrations fall above the "possible" toxicity line on the nomogram, initiate treatment within 8 hours of suspected APAP ingestion for maximal protection against hepatic injury. Give activated charcoal as soon as possible after ingestion to prevent APAP absorption. For regular-release APAP overdoses, obtain serum drug concentration at least 4 hours post-ingestion; concentrations obtained earlier than 4 hours may not represent maximum APAP concentrations. For extended-release APAP overdoses, if the initial APAP serum concentration was below the possible toxicity line, obtain a second concentration 8 to 10 hours post-ingestion. The efficacy of acetylcysteine diminishes progressively after 8 hours post-ingestion. Beginning treatment 15 to 24 hours post-ingestion results in limited efficacy; however, it does not appear to worsen the condition and should not be withheld since the reported time of ingestion may not be correct. If the time of ingestion is unknown, or the serum APAP concentration is not available, cannot be interpreted, or is not available within 8 hours of APAP ingestion, acetylcysteine should be administered immediately regardless of the quantity reported to have been ingested. If greater than 24 hours has elapsed since the APAP ingestion, the clinician should determine the appropriateness of acetylcysteine administration based on the patients liver status and clinical presentation.
    NOTE: The Rumack-Matthew nomogram is ineffective at predicting hepatotoxicity in patients who have ingested repeated supratherapeutic doses of acetaminophen over an extended period of time. In these patients, treatment should be guided by information obtained from laboratory tests, including: acetaminophen serum concentrations, liver function tests (LFTs), serum creatinine, BUN, electrolytes, bilirubin, blood glucose, and INR. Assistance may be obtained by contacting your regional poison control center at 1-800-222-1222 or the acetaminophen overdose center at 1-800-525-6115.
    Intravenous dosage:
    NOTE: Infusions beyond 21 hours should be considered when the absorption and/or half-life of acetaminophen (APAP) may be prolonged (e.g., suspected massive overdose, concurrent ingestion of other substances, patients with preexisting liver disease). In these cases, ALT/AST, INR, and APAP concentrations should be measured before the end of the 21 hour infusion. If the APAP concentration is still detectable, ALT/AST are still increasing, or the INR remains elevated, the infusion may be continued. If the infusion is extended beyond 21 hours, the treating physician should contact either the US poison center (1-800-222-1222) or a special health professional assistance line for APAP overdose (1-800-525-6115) for assistance with dosing recommendations.
    Neonates*: No specific dosage recommendations are established; data are not available for acetaminophen toxicity. Acetylcysteine 4.2 mg/kg/hour IV infusion for 24 hours was given to 10 premature neonates (gestational ages, 25 to 31 weeks) with no noted adverse effects. In addition, 6 neonates (gestational ages, 26 to 30 weeks) received infusions of 0.1 to 1.3 mg/kg/hour for 6 days also with no noted adverse effects.
    Infants and Children weighing 5 to 20 kg: 300 mg/kg total dose divided into 3 portions and given sequentially as a continuous infusion over a total of 21 hours with no significant time between portions. Divide the dose as follows: Loading Dose: 150 mg/kg in 3 mL/kg of diluent infused IV over 1 hour; Second Dose: 50 mg/kg in 7 mL/kg of diluent infused IV over 4 hours; Third Dose: 100 mg/kg in 14 mL/kg of diluent infused IV over 16 hours.
    Children and Adolescents weighing 21 to 40 kg: 300 mg/kg total dose divided into 3 portions and given sequentially as a continuous infusion over a total of 21 hours with no significant time between portions. Divide the dose as follows: Loading Dose: 150 mg/kg in 100 mL of diluent infused IV over 1 hour; Second Dose: 50 mg/kg in 250 mL of diluent infused IV over 4 hours; Third Dose: 100 mg/kg in 500 mL of diluent infused IV over 16 hours.
    Children and Adolescents weighing more than 40 kg: 300 mg/kg total dose divided into 3 portions and given sequentially as a continuous infusion over a total of 21 hours with no significant time between portions. Divide the dose as follows: Loading Dose: 150 mg/kg (Max: 15,000 mg) in 200 mL of diluent infused IV over 1 hour; Second Dose: 50 mg/kg (Max: 5,000 mg) in 500 mL of diluent infused IV over 4 hours; Third Dose: 100 mg/kg (Max: 10,000 mg) in 1000 mL of diluent infused IV over 16 hours.
    Oral dosage (Nebulizer solution):
    Children and Adolescents: 140 mg/kg PO as the loading dose, and then 70 mg/kg/dose PO every 4 hours for 17 doses starting 4 hours after loading dose. The manufacturer recommends lavage before administering acetylcysteine treatment if activated charcoal was administered; activated charcoal adsorbs acetylcysteine in vitro and may reduce its effectiveness. Any dose vomited within 1 hour of administration must be repeated.
    Oral dosage (Effervescent tablet):
    Infants and Children weighing 19 kg or less: 140 mg/kg PO once as a loading dose. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for 17 doses. The loading dose and each maintenance dose is prepared by dissolving two 2.5 gram tablets in 100 mL or water; the resulting solution has a concentration of 50 mg/mL. Any dose vomited within 1 hour of administration must be repeated.
    Children and Adolescents weighing 20 to 29 kg: 140 mg/kg PO once as a loading dose. The loading dose is prepared by dissolving one 2.5 gram tablet and three 500 mg tablets in 150 mL of water. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for 17 doses. Each maintenance dose is prepared by dissolving four 500 mg tablets in 150 mL of water. Any dose vomited within 1 hour of administration must be repeated.
    Children and Adolescents weighing 30 to 39 kg: 140 mg/kg PO once as a loading dose. The loading dose is prepared by dissolving two 2.5 gram tablets and two 500 mg tablets in 150 mL of water. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for 17 doses. Each maintenance dose is prepared by dissolving one 2.5 gram tablet and one 500 mg tablet in 150 mL of water. Any dose vomited within 1 hour of administration must be repeated.
    Children and Adolescents weighing 40 to 49 kg: 140 mg/kg PO once as a loading dose. The loading dose is prepared by dissolving two 2.5 gram tablets and four 500 mg tablets in 150 mL of water. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for 17 doses. Each maintenance dose is prepared by dissolving one 2.5 gram tablet and two 500 mg tablets in 150 mL of water. Any dose vomited within 1 hour of administration must be repeated.
    Children and Adolescents weighing 50 to 59 kg: 140 mg/kg PO once as a loading dose. The loading dose is prepared by dissolving three 2.5 gram tablets and one 500 mg tablet in 150 mL of water. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for 17 doses. Each maintenance dose is prepared by dissolving one 2.5 gram tablet and three 500 mg tablets in 150 mL of water. Any dose vomited within 1 hour of administration must be repeated.
    Children and Adolescents weighing 60 to 69 kg: 140 mg/kg PO once as a loading dose. The loading dose is prepared by dissolving four 2.5 gram tablets in 300 mL of water. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for 17 doses. Each maintenance dose is prepared by dissolving two 2.5 gram tablets in 300 mL of water. Any dose vomited within 1 hour of administration must be repeated.
    Children and Adolescents weighing 70 to 79 kg: 140 mg/kg PO once as a loading dose. The loading dose is prepared by dissolving four 2.5 gram tablets and two 500 mg tablets in 300 mL of water. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for 17 doses. Each maintenance dose is prepared by dissolving two 2.5 gram tablets and one 500 mg tablet in 300 mL of water. Any dose vomited within 1 hour of administration must be repeated.
    Children and Adolescents weighing 80 to 89 kg: 140 mg/kg PO once as a loading dose. The loading dose is prepared by dissolving five 2.5 gram tablets and one 500 mg tablet in 300 mL of water. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for 17 doses. Each maintenance dose is prepared by dissolving two 2.5 gram tablets and three 500 mg tablets in 300 mL of water. Any dose vomited within 1 hour of administration must be repeated.
    Children and Adolescents weighing 90 to 99 kg: 140 mg/kg PO once as a loading dose. The loading dose is prepared by dissolving five 2.5 gram tablets and three 500 mg tablets in 300 mL of water. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for 17 doses. Each maintenance dose is prepared by dissolving two 2.5 gram tablets and four 500 mg tablets in 300 mL of water. Any dose vomited within 1 hour of administration must be repeated.
    Children and Adolescents weighing 100 kg or more: 140 mg/kg PO once as a loading dose. The loading dose is prepared by dissolving six 2.5 gram tablets in 300 mL of water. Starting 4 hours after the loading dose, give maintenance dose of 70 mg/kg/dose PO every 4 hours for a total of 17 doses. Each maintenance dose is prepared by dissolving three 2.5 gram tablets in 300 mL of water. Any dose vomited within 1 hour of administration must be repeated. Of note, data are limited regarding dosing requirements for patients weighing more than 100 kg.

    For mucolysis of viscous or inspissated mucous secretions in patients with pulmonary conditions (e.g., pneumonia, bronchitis, cystic fibrosis, atelectasis due to mucous obstruction, and post-traumatic chest conditions) and for use during tracheostomy care, anesthesia, and diagnostic bronchograms:
    Nebulization dosage (using face mask, mouth piece, or tracheostomy):
    Infants, Children, and Adolescents: 3 to 5 mL of 20% solution or 6 to 10 mL of 10% solution, administered via nebulization 3 to 4 times daily is the recommended dosage for most patients; however, the dosage range is 1 to 10 mL of 20% solution or 2 to 20 mL of 10% solution administered every 2 to 6 hours. Dosages at the lower end of the range (e.g., 1 to 2 mL of 20% or 2 to 4 mL of 10%) may be most appropriate for infants. Administration of a bronchodilator 10 to 15 minutes prior to dose may reduce the incidence of bronchospasm.
    Nebulization dosage (using tent or croupette):
    Infants and Children: Specific dosage is dependent on the available equipment and patient need. Use a sufficient volume of 10% or 20% solution to provide a heavy mist for the desired period of time. Very large volumes (e.g., up to 300 mL) may be required. Intermittent or continuous administration for prolonged periods (e.g., overnight) may be desirable.
    Direct intratracheal instillation dosage (general dosage):
    Infants, Children, and Adolescents: 1 to 2 mL of 10% or 20% solution administered by direct instillation into the trachea as often as every hour is the general dosing for direct instillation.
    Direct intratracheal instillation dosage (for tracheostomy care):
    Infants, Children, and Adolescents: 1 to 2 mL of 10% or 20% solution directly into the tracheostomy every 1 to 4 hours for routine tracheostomy care. For instillation through percutaneous intratracheal catheter, 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours may be given by a syringe attached to the catheter.
    Direct intratracheal instillation dosage (for introduction into a specific bronchopulmonary tree segment):
    Infants, Children, and Adolescents: 2 to 5 mL of 20% solution administered via a syringe connected to a small catheter that has been placed directly into the desired segment of the bronchopulmonary tree (under local anesthesia and direct vision).
    -for diagnostic bronchial studies:
    Endotracheal or Nebulization dosage:
    Infants, Children, and Adolescents: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution administered 2 to 3 times prior to the procedure via nebulization or by intratracheal instillation.

    For the treatment of distal intestinal obstruction syndrome (DIOS)* (previously called meconium ileus equivalent):
    Oral dosage:
    Children younger than 10 years: Limited data are available; the ideal dosage has not been established. For the acute treatment of moderate DIOS episodes, some experts recommend a "Mucomyst cocktail", which consists of a phosphosoda enema followed by a clear liquid diet for 24 hours. During that 24-hour period, give 3 doses of 10% acetylcysteine 30 mL PO mixed with 30 mL of cold soda or orange juice. For recurrent DIOS, 10 mL of the 20% solution PO 4 times per day in combination with acetylcysteine enemas has also been used; most patients experienced some relief within 24 hours. For recurrent DIOS refractory to other therapies, 5 to 30 mL of the 10% solution PO 1 to 3 times daily may be used.
    Children and Adolescents 10 years and older: Limited data are available; the ideal dosage has not been established. For the acute treatment of moderate DIOS episodes, some experts recommend a "Mucomyst cocktail", which consists of a phosphosoda enema followed by a clear liquid diet for 24 hours. During that 24-hour period, give 3 doses of 10% acetylcysteine 60 mL PO mixed with cold soda or orange juice. For recurrent DIOS, 10 mL of the 20% solution PO 4 times per day in combination with acetylcysteine enemas has also been used; most patients experienced some relief within 24 hours. For recurrent DIOS refractory to other therapies, 5 to 30 mL of the 10% solution PO 1 to 3 times daily may be used.
    Rectal dosage:
    Adolescents: Limited data are available; some experts consider rectal enemas of acetylcysteine to be ineffective. One study used 50 mL of the 20% solution mixed with 50 mL of water as an enema administered 1 to 4 times per day in combination with oral therapy.

    Therapeutic Drug Monitoring:
    Acute acetaminophen toxicity:
    -Obtain acetaminophen (APAP) serum concentration at least 4 hours post-ingestion of APAP product. Plot the concentration using the Rumack-Mathew nomogram to determine whether acetylcysteine therapy is appropriate.
    -Additional initial laboratory assessments: liver function test panel, renal function parameters, and prothrombin time.
    -Periodically during therapy, continue to monitor APAP concentrations, LFTs, and fluid status. Elevated transaminase concentrations at any time should prompt examinations for liver synthetic failure, such as serial prothrombin time determination. Any signs of synthetic failure should prompt renal function testing.
    -Infusions beyond 21 hours should be considered when the absorption and/or half-life of APAP may be prolonged (e.g., suspected massive overdose, concurrent ingestion of other substances, patients with preexisting liver disease). In these cases, ALT/AST, INR, and APAP concentrations should be measured before the end of the 21 hour infusion. If the APAP concentration is still detectable, ALT/AST are still increasing, or the INR remains elevated, the infusion may be continued. If the infusion is extended beyond 21 hours, the treating physician should contact either the US poison center (1-800-222-1222) or a special health professional assistance line for APAP overdose (1-800-525-6115) for assistance with dosing recommendations.

    Maximum Dosage Limits:
    Specific maximum dosage information is not available; however, commonly used maximum doses for IV acetylcysteine are 150 mg/kg (Max: 15,000 mg) for the loading dose, 50 mg/kg (Max: 5000 mg) for the second dose, and 100 mg/kg (Max: 10,000 mg) for the third dose. Specific maximum dosage information is not available for oral or inhalational dosing.

    Patients with Hepatic Impairment Dosing
    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustment is necessary. Although there was a 3-fold increase in acetylcysteine plasma concentrations in patients with hepatic cirrhosis, the published medical literature does not indicate that the dose of acetylcysteine in patients with hepatic impairment should be reduced.

    Patients with Renal Impairment Dosing
    Specific guidelines for dosage adjustments in pediatric patients with renal impairment are not available. Some experts have recommended the following adjustment for adult patients receiving systemic therapy of 140 mg/kg load then 70 mg/kg q4h x 17 doses :
    CrCl >= 10 ml/min or CRRT: no dosage adjustment
    CrCl < 10 ml/min or peritoneal dialysis: 75% of recommended dose

    *non-FDA-approved indication

    Monograph content under development

    Mechanism of Action: Acetylcysteine has several therapeutic uses. Although the precise mechanisms of action are not fully understood, many of the mechanisms are thought to involve the free sulfhydryl groups that the drug possesses.

    Prevention of hepatotoxicity secondary to acetaminophen (APAP) overdose:
    At normal therapeutic doses, APAP is primarily metabolized through glucuronidation and sulfation to nontoxic metabolites; however, a small part is metabolized to N-acetyl-p-benzoquinoneimine (NAPQI), a hepatotoxic intermediate metabolite. Under normal circumstances, NAPQI preferentially conjugates with hepatic glutathione to form nontoxic cysteine and mercapturic acid derivatives. After an APAP overdose, the glucuronide and sulfate pathways are saturated resulting in a larger amount NAPQI to be formed. Because of the increased amount of NAPQI, glutathione stores may become depleted, and the toxic metabolite reacts with the hepatocyte to produce injury. The exact mechanism of hepatic protection is not known and most likely occurs by multiple mechanisms. Acetylcysteine contains a sulfhydryl group similar to that in glutathione. Acetylcysteine may act to maintain/restore glutathione levels, it may act an as alternate substrate for conjugation and combine with the toxic reactive metabolite, and it may blunt the hepatocellular toxicity of NAPQI.

    Mucolysis (pulmonary):
    As a mucolytic, it is believed that the free sulfhydryl groups in acetylcysteine react with the disulfide linkages of mucoproteins in bronchial secretions. When the disulfide linkages that hold together the mucoprotein, DNA, and albumin molecules rupture, depolymerization occurs, which acts to decrease the viscosity of mucus secretions of the lungs. This aids in the removal of these secretions through coughing, mechanical mechanisms, or postural drainage.

    Mucolysis (distal intestinal obstruction syndrome [DIOS]):
    Some patients with cystic fibrosis have tenacious intestinal mucus, abnormal intestinal mucoproteins, and pancreatic insufficiency, which can result in partial or complete bowel obstruction. Acetylcysteine reduces the viscosity by cleaving disulfide bonds in mucoprotein molecules. Additionally, acetylcysteine concentrations that are >= 4% are hyperosmolar and draw fluid from the intestinal wall. Both proprieties contribute to its efficacy in clearing the bowel obstruction.

    Antioxidant and cytoprotective effects:
    Antioxidants such as acetylcysteine may prevent tissue damage to various organs by scavenging oxygen free radicals or by other poorly understood mechanisms, such as stabilization of cellular signal transduction systems and reduced apoptosis (programmed cell death). Acetylcysteine is thought to enhance the effects of nitric oxide (NO) by combining with NO to form S-nitrosothiol, a potent and biologically stable vasodilator. Acetylcysteine may compete with the superoxide radical for NO and thus prevent the formation of a damaging perioxinitrite free-radical. During severe sepsis, intracellular glutathione, which is a powerful radical scavenger, is depleted. It has been proposed that acetylcysteine may act as a glutathione precursor and replenish depleted intracellular reduced glutathione concentrations, augmenting antioxidant defenses. Acetylcysteine has also been reported to enhance the activity of endothelium-derived-relaxing factor (EDRF) to improve microvascular blood flow, which may provide protection during endotoxin shock. Acetylcysteine exhibits multiple potential mechanisms of action that may limit ischemia and promote cellular repair and survival. Studies using acetylcysteine as an antioxidant for organ protection in settings of clinically-relevant heart, lung, liver, and renal ischemia continue to be pursued.

    Proposed prevention of nitrate tolerance:
    Sulfhydryl groups are also believed to be important in the response to vasodilator nitrates used in the treatment of ischemic heart disease. It is well known that tolerance to nitrates occurs after prolonged use. One proposed mechanism, based on in vitro data, is the decreased conversion of nitrates to nitric oxide, possibly due to depletion of sulfhydryl cofactors. In vivo data do not completely support this sulfhydryl-depletion hypothesis. While supplementation with acetylcysteine does augment nitrate effects in vivo, the mechanism of intracellular sulfhydryl group repletion is inadequate in explaining the reversal of nitrate tolerance; an extracellular thiol/nitrate interaction appears to enhance vasodilation. Acetylcysteine inhibits angiotensin converting enzyme (ACE) in vivo and acts as an antioxidant, two mechanisms that may preserve the function of nitroglycerin-derived nitric oxide (NO). These potential actions indicate that acetylcysteine may protect the neurohormonal or vasoconstrictive responses to nitrates, rather than act as a simple repeller of thiol stores.

    Pharmacokinetics: Acetylcysteine is administered orally, intravenously, or via inhalation. The volume of distribution and protein binding are 0.47 L/kg and 83%, respectively. Any acetylcysteine that reaches the systemic circulation is deacetylated by the liver and intracellularly in most tissues to cysteine. Most of an acetylcysteine dose is expected to be metabolized and incorporated as cysteine into cellular pools. The mean terminal half-life of the intravenous solution is 5.6 hours, while the effervescent tablets have a reported mean terminal half-life of 18.1 hours. Renal clearance accounts for roughly 30% of total clearance. After 24 hours, 22% of a radioactive dose of S-acetylcysteine is excreted in the urine. No metabolites have been identified in the urine. Only about 3% of acetylcysteine is excreted in feces.

    Affected cytochrome P450 isoenzymes: none


    -Route-Specific Pharmacokinetics
    Oral Route
    Acetylcysteine is rapidly absorbed with peak plasma concentrations reached approximately 2 hours (range, 1 to 3.5 hours) after oral administration; however, oral bioavailability is very low (approximately 9%).


    -Special Populations
    Pediatrics
    Neonates
    The mean elimination half-life of acetylcysteine is longer in newborns (11 hours) than in adults (approximately 5-6 hours).

    Hepatic Impairment
    In patients with severe liver damage (i.e., chronic cirrhosis), the mean half-life is increased by 80% while the mean clearance is decreased by 30% compared to a control group.

DISCLAIMER: This drug information content is provided for informational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Patients should always consult their physician with any questions regarding a medical condition and to obtain medical advice and treatment. Drug information is sourced from GSDD (Gold Standard Drug Database ) provided by Elsevier.

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