Acetylcysteine (injection): Difference between revisions

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{{Drugbox|
{{DrugProjectFormSinglePage
|IUPAC_name = (''R'')-2-acetamido-3-mercaptopropanoic acid
|authorTag={{DB}}
| image = Acetylcysteine.svg
|genericName=Acetylcysteine
| image2 = Acetylcysteine 3D.png
|aOrAn=an
| CAS_number=616-91-1
|drugClass=antioxidant, respiratory system agent
| ATC_prefix=R05
|indicationType=treatment
| ATC_suffix=CB01
|indication=acetaminophen overdose, adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in such conditions as [[chronic bronchopulmonary disease]] ([[chronic emphysema]], [[emphysema]] with [[bronchitis]], [[chronic asthmatic bronchitis]], [[tuberculosis]], [[bronchiectasis]] and [[primary amyloidosis]] of the lung), [[acute bronchopulmonary disease]] ([[pneumonia]], [[bronchitis]], [[tracheobronchitis]]), pulmonary complications of [[cystic fibrosis]], [[tracheostomy]] care, pulmonary complications associated with surgery, use during anesthesia, post-traumatic chest conditions, [[atelectasis]] due to mucous obstruction, diagnostic bronchial studies ([[bronchograms]], [[bronchospirometry]], and bronchial wedge catheterization)
| ATC_supplemental={{ATC|S01|XA08}} {{ATC|V03|AB23}}
|adverseReactions=[[rash]], [[urticaria]]/[[facial flushing]] and [[pruritus]], [[diarrhea]], [[nausea]], [[vomiting]]
| PubChem=12035
|blackBoxWarningTitle=<span style="color:#FF0000;">ConditionName: </span>
| DrugBank=n/a
|blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
| C=5 | H=9 | N=1 | O=3 | S=1
 
| molecular_weight = 163.19
* Content
| bioavailability = 6–10% (oral) <br /> <3% (topical)
 
| metabolism = [[hepatic]]
<!--Adult Indications and Dosage-->
| elimination_half-life = 5.6 hours (adults)</br> 11 hours (neonates)
 
| excretion =  [[renal]]
<!--FDA-Labeled Indications and Dosage (Adult)-->
| licence_EU =
|fdaLIADAdult======Acetaminophen overdose=====
| licence_US = acetylcysteine
 
| pregnancy_category = B2 ([[Australia|Aus]])
*Acetylcysteine (injection) is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen. Overdose incidences are divided into two types; Acute Ingestion or Repeated Supratherapeutic Ingestion (RSI).
| legal_status = Schedule 4 ([[Australia|Aus]])<br />[[Over-the-counter substance|OTC]] or [[Prescription drug|Rx]] ([[U.S.]])
 
| routes_of_administration= inhalation, [[IV]], oral
*On admission for suspected acetaminophen overdose, a serum blood sample should be drawn at least 4 hours after ingestion to determine the acetaminophen level and will serve as a basis for determining the need for treatment with acetylcysteine. If the patient presents after 4 hours post-ingestion, the serum acetaminophen sample should be determined immediately.
}}
 
{{CMG}}
*Acetylcysteine Injection should be administered within 8 hours from acetaminophen ingestion for maximal protection against hepatic injury for patients whose serum acetaminophen levels fall above the "possible" toxicity line on the Rumack-Matthew nomogram (line connecting 150 mcg/mL at 4 hours with 37.5 mcg/mL at 12 hours); [see Acetaminophen Assays – Interpretation and Methodology]. If the time of ingestion is unknown, or the serum acetaminophen level is not available, cannot be interpreted, or is not available within the 8 hour time interval from acetaminophen ingestion, Acetylcysteine Injection should be administered immediately if 24 hours or less have elapsed from the reported time of ingestion of an overdose of acetaminophen, regardless of the quantity reported to have been ingested.
__NOTOC__
 
{{Editor Help}}
*The [[aspartate aminotransferase]] (AST, SGOT), [[alanine aminotranferase]] (ALT, SGPT), [[bilirubin]], [[prothrombin time]], [[creatinine]], blood urea nitrogen (BUN), blood glucose, and electrolytes also should be determined in order to monitor hepatic and renal function and electrolyte and fluid balance.
 
*NOTE: The critical ingestion-treatment interval for maximal protection against severe hepatic injury is between 0 to 8 hours. Efficacy diminishes progressively after 8 hours and treatment initiation between 15 and 24 hours post-ingestion of acetaminophen yields limited efficacy. However, it does not appear to worsen the condition of patients and it should not be withheld, since the reported time of ingestion may not be correct.
 
'''Acetaminophen Assays Interpretation and Methodology – Acute Ingestion'''
 
*The acute ingestion of acetaminophen in quantities of 150 mg/kg or greater may result in hepatic toxicity. However, the reported history of the quantity of a drug ingested as an overdose is often inaccurate and is not a reliable guide to therapy of the overdose. Therefore, plasma or serum acetaminophen concentrations, determined as early as possible, but no sooner than four hours following an acute overdose, are essential in assessing the potential risk of [[hepatotoxicity]]. If an assay for acetaminophen cannot be obtained, it is necessary to assume that the overdose is potentially toxic.
 
'''Interpretation of Acetaminophen Assays'''
 
*When results of the plasma acetaminophen assay are available, refer to the nomogram in Figure 1 to determine if plasma concentration is in the potentially toxic range. Values above the line connecting 200 mcg/mL at 4 hours with 50 mcg/mL at 12 hours (probable line) are associated with a probability of hepatic toxicity if an antidote is not administered.
*If the predetoxification plasma level is above the line connecting 150 mcg/mL at 4 hours with 37.5 mcg/mL at 12 hours (possible line), continue with maintenance doses of acetylcysteine. It is better to err on the safe side and thus this line, defining possible toxicity, is plotted 25% below the line defining probable toxicity.
*If the predetoxification plasma level is below the line connecting 150 mcg/mL at 4 hours with 37.5 mcg/mL at 12 hours (possible line), there is minimal risk of hepatic toxicity, and Acetylcysteine treatment may be discontinued.
 
*Estimating Potential for [[Hepatotoxicity]]: The following depiction of the Rumack- Matthew nomogram has been developed to estimate the probability that plasma levels in relation to intervals post-ingestion will result in hepatotoxicity.
 
*The Rumack-Matthew nomogram may underestimate the risk for hepatotoxicity in some patients with risk factors such as chronic alcoholism, malnutrition, or CYP2E1 enzyme inducing drugs (e.g., isoniazid).
 
'''Figure 1. Rumack-Matthew Nomogram:'''
 
[[File:Acetylcysteine fig 1.jpg|600px|thumbnail|left]]
{{clear}}
 
*Figure 1. Michael J Hodgman, Alexander R Garrard, A Review of Acetaminophen Poisoning. Crit Care Clin. 28 (2012) 499-516. Stephen J. Wolf, Kennon Heard, et.al, Clinical Policy: Critical Issues in the Management of Patients Presenting to the Emergency Department with Acetaminophen Overdose. Ann Emerg Med. 2007:50:292-313.
 
'''Acetaminophen Assays Interpretation and Methodology – Repeated Supratherapeutic Ingestion'''
 
*Repeated Supratherapeutic Ingestion (RSI) is defined as ingestion of acetaminophen at doses higher than those recommended for extended periods of time. The nomogram does not apply to patients with RSI. Treatment is based on the acetaminophen and elevated AST/ALT levels indicative of potential toxicity due to acetaminophen. For specific treatment information regarding the clinical management of repeated supratherapeutic acetaminophen overdose, please contact your regional poison center at 1-800-222-1222, or alternatively, a special health professional assistance line for acetaminophen overdose at 1-800-525-6115.
 
'''Figure 2. Acetylcysteine Injection Treatment Flow Chart'''
 
[[File:Acetylcysteine fig 2.jpg|600px|thumbnail|left]]
{{clear}}
 
*1Acetaminophen levels drawn less than 4 hours post-ingestion may be misleading.
 
*2With an extended-release preparation, an acetaminophen level drawn less than 8 hours post-ingestion may be misleading. Draw a second level at 4 to 6 hours after the initial level. If either falls above the toxicity line, acetylcysteine treatment should be initiated.
 
*3Acetylcysteine may be withheld until acetaminophen assay results are available as long as initiation of treatment is not delayed beyond 8 hours post-ingestion. If more than 8 hours post-ingestion, start acetylcysteine treatment immediately.
 
'''Dosing Information'''
 
*The total dose of Acetylcysteine Injection is 300 mg/kg given as 3 separate doses and administered over a total of 21 hours. Please refer to the guidelines below for dose preparation based upon patient weight. The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction (see Tables 1 and 2).
 
'''Administration Instructions (Three-Bag Method: Loading, Second and Third Dose)'''
 
*Dosing for Patients who weigh 5 kg to 20 kg (Table 1):
 
*Loading Dose: 150 mg/kg diluted in 3 mL/kg of diluent* administered over 1 hr
 
*Second Dose: 50 mg/kg diluted in 7 mL/kg of diluent* administered over 4 hrs
 
*Third Dose: 100 mg/kg diluted in 14 mL/kg of diluent* administered over 16 hrs
 
[[File:Acetylcysteine t 1.png|600px|thumbnail|left]]
{{clear}}
 
*See also Section 2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction
 
*Dosing for patients who weigh 21 kg to 40 kg (Table 2):
 
*Loading Dose: 150 mg/kg diluted in 100 mL of diluent* administered over 1 hr
 
*Second Dose: 50 mg/kg diluted in 250 mL of diluent* administered over 4 hrs
 
*Third Dose: : 100 mg/kg diluted in 500 mL of diluent* administered over 16 hrs
 
[[File:Acetylcysteine t 2.png|600px|thumbnail|left]]
{{clear}}
 
*See also Section 2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction.
 
*Dosing for patients who weigh 41 kg to 100 kg (Table 3):
 
*Loading Dose: 150 mg/kg diluted in 200 mL of diluent* administered over 1 hr
 
*Second Dose: 50 mg/kg diluted in 500 mL of diluent* administered over 4 hrs
 
*Third Dose: 100 mg/kg diluted in 1,000 mL of diluent administered over 16 hrs
 
[[File:Acetylcysteine t 3.png|600px|thumbnail|left]]
{{clear}}
 
'''Patients Weighing More Than 100 kg'''
 
*No specific studies have been conducted to evaluate the use of or necessity of dosing adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg. The dose of Acetylcysteine Injection recommended in these patients should be a loading dose of 15,000 mg infused over a period of one hour followed by a first maintenance dose of 5,000 mg over 4 hours and a second maintenance dose of 10,000 mg over 16 hours (Table 3).
 
'''Continued Therapy beyond 21 Hours'''
 
*While there is no clinical trial data to support infusions beyond 21 hours there is literature that supports continued infusion of acetylcysteine in some rare instances. In cases of suspected massive overdose, or with concomitant ingestion of other substances, or in patients with preexisting liver disease, the absorption and/or the half-life of acetaminophen may be prolonged, in such cases consideration should be given to the need for continued infusion of N-acetylcysteine beyond 21 hours. Acetaminophen levels and ALT/AST & INR should be checked before the end of the 21-hour infusion. If acetaminophen levels are still detectable, or in cases in which the ALT/AST are still increasing or the INR remains elevated, the infusion should be continued, and the treating physician should contact a US regional poison center at 1-800-222-1222, or alternatively, a “special health professional assistance line for acetaminophen overdose” at 1-800-525-6115 for assistance with dosing recommendations.
 
'''Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction'''
 
*The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction. To avoid fluid overload, the volume of diluent should be reduced as clinically needed. If the volume of the infusion is not adjusted, fluid overload can occur, potentially resulting in hyponatremia, seizure and death.
 
*As Acetylcysteine Injection is hyperosmolar (2600 mOsmol/L), caution is advised when the diluent volume is decreased as the hyperosmolarity of the solution is increased. See Table 4 below for examples.
 
[[File:Acetylcysteine t 4.png|600px|thumbnail|left]]
{{clear}}
 
*Single dose vial, preservative-free, discard unused portion. If vial was previously opened, do not use for intravenous administration.
 
*Stability studies indicate that the diluted solution is stable for 24 hours at controlled room temperature.
 
*Note: The color of Acetylcysteine Injection may turn from essentially colorless to a slight pink or purple once the stopper is punctured. The color change does not affect the quality of the product.
 
'''Renal Impairment'''
 
*No data are available to determine if a dose adjustment in patients with moderate or severe renal impairment is required.
 
'''Hepatic Impairment'''
 
*Although there was a threefold increase in acetylcysteine plasma concentrations in patients with [[hepatic cirrhosis]], no data are available to determine if a dose adjustment in these patients is required. The published medical literature does not indicate that the dose of acetylcysteine in patients with hepatic impairment should be reduced.
 
'''DOSAGE FORMS & STRENGTHS'''
 
*Each single dose vial contains 6g/30mL (200 mg/mL) of Acetylcysteine. Acetylcysteine Injection is sterile and can be used for intravenous administration.
 
=====Administration of anesthesia for procedure=====
 
* Dosing Information
 
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
 
=====Atelectasis, Due to mucous obstruction=====
 
* Dosing Information
 
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
 
=====Bronchopulmonary disease, acute=====
 
* Dosing Information
 
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
 
====Complication of surgical procedure - Respiratory complication====
 
* Dosing Information
 
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
 
====Cystic fibrosis, Pulmonary complications; Adjunct====
 
* Dosing Information
 
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
 
====Diagnostic procedure on lower respiratory tract====
 
* Dosing Information
 
:*Diagnostic bronchial studies: 1 to 2 mL of the 20% solution or 2 to 4 mL of the 10% solution 2 or 3 times prior to the procedure by nebulization or by instillation intratracheally
 
====Disease of respiratory system, chronic====
 
* Dosing Information
 
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Disease of respiratory system, chronic: direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Disease of respiratory system, chronic: percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Disease of respiratory system, chronic: intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
 
====Tracheostomy care====
 
* Dosing Information
 
:*Nebulization into tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
|offLabelAdultGuideSupport=* There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=* There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
 
<!--Pediatric Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Acetaminophen overdose=====
 
* Dosing Information
 
:*Oral: initial, 140 mg/kg ORALLY, then 70 mg/kg every 4 hours for 17 doses starting 4 hours after loading dose
:*IV: body weight 5 to 20 kg: loading dose, 150 mg/kg in 3 mL/kg of compatible solution (D5W, 0.45%NaCl, or sterile water for injection) IV over 60 minutes, then 50 mg/kg in 7 mL/kg of compatible solution IV over 4 hours, followed by 100 mg/kg in 14 mL/kg of compatible solution IV over 16 hours; may continue beyond 21 hours if clinically indicated; adjust the total volume administered for patients requiring fluid restriction as clinically necessary
:*IV: body weight 21 kg to 40 kg: loading dose, 150 mg/kg in 100 mL of compatible solution (D5W, 0.45%NaCl, or sterile water for injection) IV over 60 minutes, then 50 mg/kg in 250 mL of compatible solution IV over 4 hours, followed by 100 mg/kg in 500 mL of compatible solution IV over 16 hours; may continue beyond 21 hours if clinically indicated; adjust the total volume administered for patients less than 40 kg or requiring fluid restriction as clinically necessary
:*IV: body weight 41 to 100 kg, loading dose, 150 mg/kg in 200 mL of compatible solution (D5W, 0.45%NaCl, or sterile water for injection) IV over 60 minutes, then 50 mg/kg in 500 mL of compatible solution IV over 4 hours, followed by 100 mg/kg in 1000 mL of solution IV over 16 hours; may continue beyond 21 hours if clinically indicated; adjust the total volume administered for patients requiring fluid restriction as clinically necessary [3]
:*IV: body weight over 100 kg, loading dose, 15,000 mg in 200 mL of compatible solution (D5W, 0.45%NaCl, or sterile water for injection) IV over 60 minutes, then 5000 mg in 500 mL of compatible solution IV over 4 hours, followed by 10,000 mg in 1000 mL of solution IV over 16 hours; may continue beyond 21 hours if clinically indicated; adjust the total volume administered for patients requiring fluid restriction as clinically necessary
 
=====Administration of anesthesia for procedure=====
 
* Dosing Information
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
 
====Atelectasis, Due to mucous obstruction====


==Overview==
* Dosing Information
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter


'''Acetylcysteine''' ([[International Nonproprietary Name|rINN]]; {{pronEng|ˌæsɛtəlˈsɪstiːn, əˌsɛtəl-}}), also known as '''''N''-acetylcysteine''' or '''''N''-acetyl-L-cysteine''' (abbreviated '''NAC'''), is a pharmacological agent used mainly as a [[mucolytic]] and in the management of [[paracetamol]] (acetaminophen) overdose. For these indications, it is available under the trade names '''ACC''' ([[Sandoz|Hexal AG]]), '''Mucomyst''' ([[Bristol-Myers Squibb]]), '''Acetadote''' (Cumberland Pharmaceuticals), '''Fluimucil''' ([[Zambon]]),  '''Parvolex''' ([[GlaxoSmithKline|GSK]]), '''Lysox''' ([[Menarini]]) and '''Mucolysin''' ([[Sandoz]]).
====Bronchopulmonary disease, acute====


==Dosage forms==
* Dosing Information
Acetylcysteine is available in different dosage forms for different indications:
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
*Solution for inhalation (Mucomyst, Mucosil) – inhaled for mucolytic therapy or ingested for nephroprotective effect (to protect the kidneys)
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
*[[intravenous therapy|IV]] injection (Parvolex, Acetadote) – treatment of paracetamol/acetaminophen overdose
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
*Oral solution – various indications
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter


The IV injection and inhalation preparations are, in general, prescription only, whereas the oral solution is available [[over-the-counter substance|over the counter]] in many countries.
====Complication of surgical procedure - Respiratory complication====


==Clinical use==
* Dosing Information
===Mucolytic therapy===
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
Inhaled acetylcysteine is indicated for mucolytic ("mucus-dissolving") therapy as an adjuvant in respiratory conditions with excessive and/or thick mucus production. Such conditions include [[emphysema]], [[bronchitis]], [[tuberculosis]], [[bronchiectasis]], [[amyloidosis]], [[pneumonia]]. It is also used post-operatively, as a diagnostic aid, and in [[tracheostomy]] care. It may be considered ineffective in [[cystic fibrosis]] (Rossi, 2006).  However, a recent paper in the Proceedings of the National Academy of Sciences reports that high-dose oral N-acetylcysteine modulates inflammation in cystic fibrosis and has the potential to counter the intertwined redox and inflammatory imbalances in CF (Tirouvanziam et al., 2006). Oral acetylcysteine may also be used as a mucolytic in less serious cases.
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter


For this indication, acetylcysteine acts to reduce mucus viscosity by splitting [[disulfide bond]]s linking proteins present in the mucus (mucoproteins).
====Cystic fibrosis, Pulmonary complications; Adjunct====


===Paracetamol (Acetaminophen) overdose===
* Dosing Information
Intravenous acetylcysteine is indicated for the treatment of [[paracetamol]] (acetaminophen) overdose. When paracetamol is taken in large quanities, a minor metabolite called N-methyl-p-benzoquinone imine ([[NAPQI]]) builds up.  It is normally [[Xenobiotic_metabolism#Phase_II_-_conjugation|conjugated]] by [[glutathione]], but when taken in excess (especially in alcoholics), the body's glutathione reserves are not sufficient to inactivate the toxic NAPQI.  This metabolite is then free to react with key hepatic enzymes, therefore damaging hepatocytes.  This may lead to severe liver damage and even death by [[fulminant]] [[liver failure]].
:*Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter


For this indication, acetylcysteine acts to augment the glutathione reserves in the body and, together with glutathione, directly bind to toxic metabolites. These actions serve to protect [[hepatocyte]]s in the liver from NAPQI toxicity.
====Diagnostic procedure on lower respiratory tract====


Although both IV and oral acetylcysteine are equally effective for this indication, oral administration is uncommon, as it is poorly tolerated, owing to the high doses required (due to low oral [[bioavailability]]), very unpleasant taste and odour, and [[adverse drug reaction|adverse effect]]s (particularly nausea and vomiting). However, 3% to 6% of people given intravenous acetylcysteine show a severe, [[anaphylaxis]]-like allergic reaction, which may include extreme breathing difficulty (due to [[bronchospasm]]), [[hypotension|a decrease in blood pressure]], rash, [[angioedema]], and sometimes also nausea and vomiting (Kanter, 2006). Repeated overdoses will cause the allergic reaction to get worse and worse. Several studies have found this anaphylaxis-like reaction to occur more often in people given IV acetylcysteine despite serum levels of paracetamol not high enough to be considered toxic (Dawson et al., 1989; Bailey & McGuigan, 1998; Schmidt & Dalhoff, 2001; Lynch & Robertson, 2004).
* Dosing Information
:*Diagnostic bronchial studies: 1 to 2 mL of the 20% solution or 2 to 4 mL of the 10% solution 2 or 3 times prior to the procedure by nebulization or by instillation intratracheally


In some countries, a specific intravenous formulation does not exist to treat [[paracetamol]] overdose. In these cases, the formulation used for inhalation may be used intravenously.
====Disease of respiratory system, chronic====


===Nephroprotective agent===
* Dosing Information
Oral acetylcysteine is used for the prevention of [[radiocontrast]]-induced nephropathy (a form of [[acute renal failure]]). Some studies show that prior administration of acetylcysteine markedly decreases (90%) radiocontrast nephropathy (Tepel ''et al'' 2000), whereas others appear to cast doubt on its efficacy (Hoffman ''et al.'', 2004; Miner ''et al.'', 2004).  Worth considering is the newest data published in two papers in the ''New England Journal of Medicine''  and the ''Journal of the American Medical Association.''  The authors' conclusions in those papers were: 1) "Intravenous and oral N-acetylcysteine may prevent contrast-medium–induced nephropathy with a dose-dependent effect in patients treated with primary angioplasty and may improve hospital outcome." (Marenzi et al, 2006)
:* Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
2) "Acetylcysteine protects patients with moderate chronic renal insufficiency from contrast-induced deterioration in renal function after coronary angiographic procedures, with minimal adverse effects and at a low cost" (Kay et al., 2003).
:*Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter


Acetylcysteine continues to be commonly used in individuals with [[chronic renal failure|renal impairment]] to prevent the precipitation of acute renal failure.
====Tracheostomy care====


==Investigational==
* Dosing Information
The following uses have not been well-established or investigated:
:*Nebulization into tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
* NAC is undergoing [[clinical trial]]s in the [[United States]] for the treatment of [[obsessive-compulsive disorder]].<ref>[http://clinicaltrials.gov/ct/show/NCT00539513?order=2 N-Acetylcysteine Augmentation in Treatment-Refractory Obsessive-Compulsive Disorder - Full Text View - ClinicalTrials.gov<!-- Bot generated title -->]</ref> It is thought to counteract the [[glutamate]] hyperactivity in OCD.
:*Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
* NAC has been shown to reduce cravings associated with chronic [[cocaine]] use in a study conducted at the [[Medical University of South Carolina]] (Mardikian ''et al'', 2007; LaRowe et al, 2007)
:*Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
* It may reduce the incidence of [[chronic obstructive pulmonary disease]] (COPD) exacerbations (Pela ''et al.'', 1999)
:*Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
* In the treatment of [[AIDS]], NAC has been shown to cause a "marked increase in immunological functions and plasma albumin concentrations" (Breitkreutz & al, 2000). Albumin concentration are inversely correlated with muscle wasting ([[cachexia]]), a condition associated with AIDS.
|offLabelPedGuideSupport=*There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
* An animal study indicates that acetylcysteine may decrease mortality associated with [[influenza]] (Ungheri ''et al.'', 2000)
* Animal studies suggest that NAC may help prevent noise-induced hearing loss (Kopke ''et al.'', 2005).    A clinical trial to determine efficacy in preventing noise-induced sensorineural hearing loss in humans is currently (2006) being jointly conducted by the US Army and US Navy.
* It has been suggested that NAC may help sufferers of [[Samter's triad]] by increasing levels of glutathione allowing faster breakdown of [[salicylate]]s, though there is no evidence that it is of benefit (Bachert ''et al.'', 2003).
* There are claims that acetylcysteine taken together with vitamin C and B1 can be used to prevent and relieve symptoms of [[veisalgia]] (hangover following [[ethanol]] (alcohol) consumption). The claimed mechanism is through scavenging of [[acetaldehyde]], a toxic intermediate in the metabolism of ethanol.
* It has been shown to help women with PCOS (polycystic ovary syndrome) to reduce insulin problems and possibly improve fertility. (Fulghesu, ''et al'', 2002)


==Chemistry==
<!--Non–Guideline-Supported Use (Pediatric)-->
Acetylcysteine is the ''N''-[[acetyl]] derivative of the amino acid <small>L</small>-[[cysteine]], and is a precursor in the formation of the antioxidant [[glutathione]] in the body. The [[thiol]] (sulfhydryl) group confers antioxidant effects and is able to [[Redox|reduce]] [[free radical]]s.
|offLabelPedNoGuideSupport=* There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.


==Possible toxicity==
<!--Contraindications-->
Researchers at the [[University of Virginia]] recently reported that acetylcysteine, which is found in many [[bodybuilding supplements]], could potentially cause damage to the [[heart]] and [[lungs]] (Palmer et al., 2007). They found that acetylcysteine was [[drug metabolism|metabolized]] to ''S''-nitroso-''N''-acetylcysteine (SNOAC), which increased [[blood pressure]] in the lungs and [[right ventricle]] of the heart ([[pulmonary artery hypertension]]) in [[mice]] treated with acetylcysteine. The effect was similar to that observed following a 3-week exposure to an oxygen-deprived environment (chronic [[hypoxia (medical)|hypoxia]]). The authors also found that SNOAC induced a hypoxia-like response in the [[gene expression|expression]] of several important [[gene]]s both ''[[in vitro]]'' and ''[[in vivo]]''.
|contraindications=* Acetylcysteine Injection is contraindicated in patients with previous anaphylactoid reactions to acetylcysteine.
<!--Warnings-->
|warnings='''Anaphylactoid Reactions'''


The implications of these findings for long-term treatment with acetylcysteine have not yet been investigated. The dose used by Palmer and colleagues (2007) was dramatically higher than that used in humans; nonetheless, the drug's effects on the [[control of respiration|hypoxic ventilatory response]] have been observed previously in human subjects at more moderate doses (Hildebrandt et al., 2002).
*Serious anaphylactoid reactions, including death in a patient with asthma, have been reported in patients administered acetylcysteine intravenously.
*Acute [[flushing]] and [[erythema]] of the skin may occur in patients receiving acetylcysteine intravenously. These reactions usually occur 30 to 60 minutes after initiating the infusion and often resolve spontaneously despite continued infusion of acetylcysteine. Anaphylactoid reactions (defined as the occurrence of an acute hypersensitivity reaction during acetylcysteine administration including [[rash]], [[hypotension]], [[wheezing]], and/or [[shortness of breath]]) have been observed in patients receiving intravenous acetylcysteine for acetaminophen overdose and occurred soon after initiation of the infusion.If a reaction to acetylcysteine involves more than simply [[flushing]] and [[erythema]] of the skin, it should be treated as an anaphylactoid reaction. This usually entails administering antihistaminic drugs and in severe cases may require administration of [[epinephrine]]. In addition, the acetylcysteine infusion may be interrupted until treatment of the anaphylactoid symptoms has been initiated and then carefully restarted. If the anaphylactoid reaction returns upon reinitiation of treatment or increases in severity, intravenous acetylcysteine should be discontinued and alternative patient management should be considered.


==References==
'''Monitoring patients with asthma'''
*Acetylcysteine Injection should be used with caution in patients with [[asthma]], or where there is a history of bronchospasm.


<references/>
'''Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction'''


==Additional Resources==
*The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction. To avoid fluid overload, the volume of diluent should be reduced as needed. If volume is not adjusted [[fluid overload]] can occur, potentially resulting in hyponatremia, seizure and death.
<small> <div style="-moz-column-count:2; column-count:2;">
* Bachert C, Hormann K, Mosges R, ''et al.'' "An update on the diagnosis and treatment of sinusitis and nasal polyposis." ''Allergy'' 2003;58(3):176-91. PMID 12653791
*For specific treatment information regarding the clinical management of acetaminophen overdose, please contact your regional poison center at 1-800-222-1222, or alternatively, a special health professional assistance line for acetaminophen overdose at 1-800-525-6115.
* Bailey B, McGuigan MA. Management of anaphylactoid reactions to intravenous N-acetylcysteine. Ann Emerg Med. 1998 Jun;31(6):710–5. PMID 9624310
* Breitkreutz R, Pittack N, Nebe CT, Schuster D, Brust J, Beichert M, Hack V, Daniel V, Edler L, Droge W. "Improvement of immune functions in HIV infection by sulfur supplementation: two randomized trials." ''J Mol Med'' 2000;78(1):55-62. PMID 10759030
* Dawson AH, Henry DA, McEwen J. Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning. Med J Aust. 1989 Mar 20;150(6):329–31. PMID 2716644
* Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, Lanzone A. "N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome." ''Fertility and Sterility'' 2002 Jun;77(6):1128-35. PMID 12057717
* Hildebrandt W, Alexander S, Bärtsch P, Dröge W. "[http://bloodjournal.hematologylibrary.org/cgi/content/full/99/5/1552 Effect of N-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O(2) chemosensitivity.]" ''Blood'' 2002 Mar 1;99(5):1552-5. Accessed [[November 12]], [[2007]]. PMID 11861267
* Hoffmann U, Fischereder M, Kruger B, Drobnik W, Kramer BK. "The value of N-acetylcysteine in the prevention of radiocontrast agent-induced nephropathy seems questionable." ''J Am Soc Nephrol'' 2004;15:407-10. [http://www.jasn.org/cgi/content/full/15/2/407 Fulltext]. PMID 14747387.
* Kanter MZ. "[http://www.ajhp.org/cgi/content/full/63/19/1821 Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning.]" ''Am J Health Syst Pharm'' 2006;63(19):1821–7. PMID 16990628. {{DOI|10.2146/ajhp060050}}
* Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yip A, Fan K, Lee CH, Lam WF. "[http://jama.ama-assn.org/cgi/content/full/289/5/553 Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: a randomized controlled trial.]" ''Journal of the American Medical Association'' 2003 Feb 5;289(5):553-8. Accessed [[December 12]], [[2007]]. PMID 12578487
* Kopke R, Bielefeld E, Liu J, ''et al.'' "Prevention of impulse noise-induced hearing loss with antioxidants." ''Acta Otolaryngol'' 2005;125(3):235-43. PMID 15966690
* LaRowe SD, Myrick H, Hedden S, Mardikian P, Saladin M, McRae A, Brady K, Kalivas PW, Malcolm R. "Is cocaine desire reduced by N-acetylcysteine?" ''Am J Psychiatry''. 2007 Jul;164(7):1115-7. PMID 17606664
* Lynch RM, Robertson R. Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study. Accid Emerg Nurs. 2004 Jan;12(1):10–5. PMID 14700565
* Mardikian PN, LaRowe SD, Hedden S, Kalivas PW, Malcolm RJ. "An open-label trial of N-acetylcysteine for the treatment of cocaine dependence: a pilot study." Prog Neuropsychopharmacol Biol Psychiatry. 2007 Mar 30;31(2):389-94. PMID 17113207
* Marenzi G, Assanelli E, Marana I, Lauri G, Campodonico J, Grazi M, De Metrio M, Galli S, Fabbiocchi F, Montorsi P, Veglia F, Bartorelli AL. "N-acetylcysteine and contrast-induced nephropathy in primary angioplasty." ''N Engl J Med.'' 2006 Jun 29;354(26):2773-82. PMID 16807414
* Miner SE, Dzavik V, Nguyen-Ho P, Richardson R, Mitchell J, Atchison D, Seidelin P, Daly P, Ross J, McLaughlin PR, Ing D, Lewycky P, Barolet A, Schwartz L. "N-acetylcysteine reduces contrast-associated nephropathy but not clinical events during long-term follow-up." ''Am Heart J'' 2004;148:690-5. PMID 15459602.
* Palmer LA, Doctor A, Chhabra P, Sheram ML, Laubach VE, Karlinsey MZ, Forbes MS, Macdonald T, Gaston B. "[http://www.jci.org/cgi/content/full/117/9/2592 S-nitrosothiols signal hypoxia-mimetic vascular pathology.]" ''Journal of Clinical Investigation'' 2007 Sep;117(9): 2592-601. Accessed [[December 12]], [[2007]]. PMID 17786245
* Pela R, Calcagni AM, Subiaco S, ''et al.'' "N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD." ''Respiration'' 1999;66(6):495-500. PMID 10575333
* Rossi S, editor. [[Australian Medicines Handbook]] 2006. Adelaide: Australian Medicines Handbook; 2006.
* Schmidt LE, Dalhoff K. Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning. Br J Clin Pharmacol. 2001 Jan;51(1):87–91. PMID 11167669
* Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D, Zidek W. "Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine." ''[[N Engl J Med]]'' 2000;343:180-4. PMID 10900277.
* Tirouvanziam R, Conrad CK, Bottiglieri T, Herzenberg LA, Moss RB, Herzenberg LA. "[http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=16537378 High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis.]" Proc Natl Acad Sci USA. 2006 Mar 21;103(12):4628-33. PMID 16537378
* Ungheri D, Pisani C, Sanson G, ''et al.'' "Protective effect of n-acetylcysteine in a model of influenza infection in mice." ''Int J Immunopathol Pharmacol'' 2000;13(3):123-128. PMID 12657201
</div> </small>


==See also==
*After proper administration of acetylcysteine, an increased volume of liquified bronchial secretions may occur. When cough is inadequate, the open airway must be maintained by mechanical suction if necessary. When there is a mechanical block due to foreign body or local accumulation, the airway should be cleared by endotracheal aspiration, with or without bronchoscopy. Asthmatics under treatment with acetylcysteine should be watched carefully. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, this medication should be discontinued immediately.
*[[Glutathione]]
*[[Cysteine]]


==External links==
<!--Adverse Reactions-->
*[http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500403.html MedlinePlus drug information: Acetylcysteine (inhalation)] – information from USP DI Advice for the Patient


{{Cough and cold preparations}}
<!--Clinical Trials Experience-->
|drugBox={{Drugbox2
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 443366456
| IUPAC_name = (2''R'')-2-acetamido-3-sulfanylpropanoic acid<ref>{{cite web|title=L-Cysteine, N-acetyl- - Compound Summary|url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=581|work=PubChem Compound|publisher=National Center for Biotechnology Information|accessdate=9 January 2012|location=USA|date=25 March 2005|at=Identification}}</ref>
| image = Acetylcysteine2DACS.png
| width = 125
| image2 = Acetylcysteine3Dan3.gif
| width2 = 200
| imagename =
| drug_name =
| caption =


{{Antidotes}}
<!-- Clinical data -->
| tradename = Acetadote, Fluimucil, Mucomyst, Parvolex
| Drugs.com = {{drugs.com|monograph|acetylcysteine}}
| MedlinePlus =
| licence_EU = <!-- EMA requires brand name -->
| licence_US = Acetylcysteine
| DailyMedID = 5558a5f5-e821-473b-7d8a-5d33d09f0586
| pregnancy_AU = B2
| pregnancy_US = B
| legal_AU = S2
| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL, P, POM, CD, CD Lic, CD POM, CD No Reg POM, CD (Benz) POM, CD (Anab) POM or CD Inv POM -->
| legal_US = Rx-only
| routes_of_administration = Oral, injection, inhalation


[[Category:Antioxidants]]
<!-- Pharmacokinetic data -->
[[Category:Antidotes]]
| bioavailability = 4-10% (Oral)<ref name = DMO>{{cite web|title=ACETYLCYSTEINE solution [Fresenius Kabi USA, LLC]|work=DailyMed|publisher=Fresenius Kabi USA, LLC|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=75b48fab-cef6-465c-a1e0-d085b3988bc4|date=September 2013|accessdate=8 November 2013}}</ref><ref name = DMI>{{cite web|title=ACETADOTE (acetylcysteine) injection, solution [Cumberland Pharmaceuticals Inc.]|work=DailyMed|publisher=Cumberland Pharmaceuticals Inc.|date=June 2013|accessdate=8 November 2013|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=472f158a-5ab9-4308-8e49-1116e6ea3d39}}</ref><ref name = MD>{{cite book|title=Acetylcysteine|work=Martindale: The Complete Drug Reference|publisher=The Royal Pharmaceutical Society of Great Britain|url=http://www.medicinescomplete.com/mc/martindale/current/ms-3701-r.htm|date=16 November 2012|accessdate=8 November 2013}}</ref><ref name = TGA>{{cite web|title=PRODUCT INFORMATION ACETADOTE® CONCENTRATED INJECTION|work=TGA eBusiness Services|publisher=Phebra Pty Ltd|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03960-3|format=PDF|date=16 January 2013|accessdate=8 November 2013}}</ref><ref name="pmid3803419">{{cite journal | author = Borgström L, Kågedal B, Paulsen O | title = Pharmacokinetics of N-acetylcysteine in man | journal = Eur. J. Clin. Pharmacol. | volume = 31 | issue = 2 | pages = 217–22 | year = 1986 | pmid = 3803419 | doi = 10.1007/BF00606662 }}</ref>
| protein_bound = 80-83%<ref name = DMO/><ref name = DMI/><ref name = MD/><ref name = TGA/><ref name="pmid3803419"/>
| metabolism = [[Hepatic]]<ref name = DMO/><ref name = DMI/><ref name = MD/><ref name = TGA/><ref name="pmid3803419"/>
| elimination_half-life = 5.6 hours<ref name = DMO/><ref name = DMI/><ref name = MD/><ref name = TGA/><ref name="pmid3803419"/>
| excretion = Renal (22%), faecal (3%)<ref name = DMO/><ref name = DMI/><ref name = MD/><ref name = TGA/><ref name="pmid3803419"/>


[[ar:أستيل سستين]]
<!-- Identifiers -->
[[da:Acetylcystein]]
| CAS_number_Ref = {{cascite|changed|??}}
[[de:Acetylcystein]]
| CAS_number = 7218-04-4
[[fr:Acétylcystéine]]
| CAS_supplemental =
[[pl:Acetylocysteina]]
| ATC_prefix = R05
[[pt:Acetilcisteína]]
| ATC_suffix = CB01
[[sv:Acetylcystein]]
| ATC_supplemental = {{ATC|S01|XA08}} {{ATC|V03|AB23}}
| PubChem = 581
| PubChemSubstance =
| IUPHAR_ligand =
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB06151
| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
| ChemSpiderID = 561
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = WYQ7N0BPYC
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00221
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 28939
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 600
| synonyms =


<!-- Chemical data -->
| chemical_formula =
| C=5 | H=9 | Ag= | As= | Au= | B= | Bi= | Br= | Cl= | Co= | F= | Fe= | Gd= | I=
| K= | Mn= | N=1 | Na= | O=3 | P= | Pt= | S=1 | Sb= | Se= | Sr= | Tc= | Zn= | charge=
| molecular_weight = 163.195
| smiles = CC(=O)NC(CS)C(O)=O
| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
| StdInChI = 1S/C5H9NO3S/c1-3(7)6-4(2-10)5(8)9/h4,10H,2H2,1H3,(H,6,7)(H,8,9)
| StdInChI_comment =
| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
| StdInChIKey = PWKSKIMOESPYIA-UHFFFAOYSA-N
| density =
| melting_point = 106
| melting_high =
| melting_notes =
| boiling_point = 108
| boiling_notes =
| solubility = 200
| specific_rotation =
| sec_combustion =
}}
|structure=: [[File:Acetyl cystine structure.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
|packLabel=[[File:ACETYLCYSTEINE0001.jpeg|thumb|none|400px|This image is provided by the National Library of Medicine.]]
[[File:ACETYLCYSTEINE0002.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]


{{jb1}}
|alcohol=Alcohol-Acetylcysteine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
{{WikiDoc Help Menu}}
|brandNames=* ACETYLCYSTEINE®<ref>{{Cite web | title = ACETYLCYSTEINE- acetylcysteine injection  | url =http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4072b547-c242-4a40-8c91-5481b86cbf1e }}</ref>
{{WikiDoc Sources}}
}}
[[Category:Drug]]
[[Category:Antioxidants]]
[[Category:Antidotes]]
[[Category:Thiols]]
[[Category:Excipients]]

Latest revision as of 22:41, 14 May 2015

Acetylcysteine (injection)
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Deepika Beereddy, MBBS [2]

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Overview

Acetylcysteine (injection) is an antioxidant, respiratory system agent that is FDA approved for the treatment of acetaminophen overdose, adjuvant therapy for patients with abnormal, viscid, or inspissated mucous secretions in such conditions as chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis and primary amyloidosis of the lung), acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis), pulmonary complications of cystic fibrosis, tracheostomy care, pulmonary complications associated with surgery, use during anesthesia, post-traumatic chest conditions, atelectasis due to mucous obstruction, diagnostic bronchial studies (bronchograms, bronchospirometry, and bronchial wedge catheterization). Common adverse reactions include rash, urticaria/facial flushing and pruritus, diarrhea, nausea, vomiting.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Acetaminophen overdose
  • Acetylcysteine (injection) is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen. Overdose incidences are divided into two types; Acute Ingestion or Repeated Supratherapeutic Ingestion (RSI).
  • On admission for suspected acetaminophen overdose, a serum blood sample should be drawn at least 4 hours after ingestion to determine the acetaminophen level and will serve as a basis for determining the need for treatment with acetylcysteine. If the patient presents after 4 hours post-ingestion, the serum acetaminophen sample should be determined immediately.
  • Acetylcysteine Injection should be administered within 8 hours from acetaminophen ingestion for maximal protection against hepatic injury for patients whose serum acetaminophen levels fall above the "possible" toxicity line on the Rumack-Matthew nomogram (line connecting 150 mcg/mL at 4 hours with 37.5 mcg/mL at 12 hours); [see Acetaminophen Assays – Interpretation and Methodology]. If the time of ingestion is unknown, or the serum acetaminophen level is not available, cannot be interpreted, or is not available within the 8 hour time interval from acetaminophen ingestion, Acetylcysteine Injection should be administered immediately if 24 hours or less have elapsed from the reported time of ingestion of an overdose of acetaminophen, regardless of the quantity reported to have been ingested.
  • NOTE: The critical ingestion-treatment interval for maximal protection against severe hepatic injury is between 0 to 8 hours. Efficacy diminishes progressively after 8 hours and treatment initiation between 15 and 24 hours post-ingestion of acetaminophen yields limited efficacy. However, it does not appear to worsen the condition of patients and it should not be withheld, since the reported time of ingestion may not be correct.

Acetaminophen Assays Interpretation and Methodology – Acute Ingestion

  • The acute ingestion of acetaminophen in quantities of 150 mg/kg or greater may result in hepatic toxicity. However, the reported history of the quantity of a drug ingested as an overdose is often inaccurate and is not a reliable guide to therapy of the overdose. Therefore, plasma or serum acetaminophen concentrations, determined as early as possible, but no sooner than four hours following an acute overdose, are essential in assessing the potential risk of hepatotoxicity. If an assay for acetaminophen cannot be obtained, it is necessary to assume that the overdose is potentially toxic.

Interpretation of Acetaminophen Assays

  • When results of the plasma acetaminophen assay are available, refer to the nomogram in Figure 1 to determine if plasma concentration is in the potentially toxic range. Values above the line connecting 200 mcg/mL at 4 hours with 50 mcg/mL at 12 hours (probable line) are associated with a probability of hepatic toxicity if an antidote is not administered.
  • If the predetoxification plasma level is above the line connecting 150 mcg/mL at 4 hours with 37.5 mcg/mL at 12 hours (possible line), continue with maintenance doses of acetylcysteine. It is better to err on the safe side and thus this line, defining possible toxicity, is plotted 25% below the line defining probable toxicity.
  • If the predetoxification plasma level is below the line connecting 150 mcg/mL at 4 hours with 37.5 mcg/mL at 12 hours (possible line), there is minimal risk of hepatic toxicity, and Acetylcysteine treatment may be discontinued.
  • Estimating Potential for Hepatotoxicity: The following depiction of the Rumack- Matthew nomogram has been developed to estimate the probability that plasma levels in relation to intervals post-ingestion will result in hepatotoxicity.
  • The Rumack-Matthew nomogram may underestimate the risk for hepatotoxicity in some patients with risk factors such as chronic alcoholism, malnutrition, or CYP2E1 enzyme inducing drugs (e.g., isoniazid).

Figure 1. Rumack-Matthew Nomogram:

  • Figure 1. Michael J Hodgman, Alexander R Garrard, A Review of Acetaminophen Poisoning. Crit Care Clin. 28 (2012) 499-516. Stephen J. Wolf, Kennon Heard, et.al, Clinical Policy: Critical Issues in the Management of Patients Presenting to the Emergency Department with Acetaminophen Overdose. Ann Emerg Med. 2007:50:292-313.

Acetaminophen Assays Interpretation and Methodology – Repeated Supratherapeutic Ingestion

  • Repeated Supratherapeutic Ingestion (RSI) is defined as ingestion of acetaminophen at doses higher than those recommended for extended periods of time. The nomogram does not apply to patients with RSI. Treatment is based on the acetaminophen and elevated AST/ALT levels indicative of potential toxicity due to acetaminophen. For specific treatment information regarding the clinical management of repeated supratherapeutic acetaminophen overdose, please contact your regional poison center at 1-800-222-1222, or alternatively, a special health professional assistance line for acetaminophen overdose at 1-800-525-6115.

Figure 2. Acetylcysteine Injection Treatment Flow Chart

  • 1Acetaminophen levels drawn less than 4 hours post-ingestion may be misleading.
  • 2With an extended-release preparation, an acetaminophen level drawn less than 8 hours post-ingestion may be misleading. Draw a second level at 4 to 6 hours after the initial level. If either falls above the toxicity line, acetylcysteine treatment should be initiated.
  • 3Acetylcysteine may be withheld until acetaminophen assay results are available as long as initiation of treatment is not delayed beyond 8 hours post-ingestion. If more than 8 hours post-ingestion, start acetylcysteine treatment immediately.

Dosing Information

  • The total dose of Acetylcysteine Injection is 300 mg/kg given as 3 separate doses and administered over a total of 21 hours. Please refer to the guidelines below for dose preparation based upon patient weight. The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction (see Tables 1 and 2).

Administration Instructions (Three-Bag Method: Loading, Second and Third Dose)

  • Dosing for Patients who weigh 5 kg to 20 kg (Table 1):
  • Loading Dose: 150 mg/kg diluted in 3 mL/kg of diluent* administered over 1 hr
  • Second Dose: 50 mg/kg diluted in 7 mL/kg of diluent* administered over 4 hrs
  • Third Dose: 100 mg/kg diluted in 14 mL/kg of diluent* administered over 16 hrs
  • See also Section 2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction
  • Dosing for patients who weigh 21 kg to 40 kg (Table 2):
  • Loading Dose: 150 mg/kg diluted in 100 mL of diluent* administered over 1 hr
  • Second Dose: 50 mg/kg diluted in 250 mL of diluent* administered over 4 hrs
  • Third Dose: : 100 mg/kg diluted in 500 mL of diluent* administered over 16 hrs
  • See also Section 2.2 Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction.
  • Dosing for patients who weigh 41 kg to 100 kg (Table 3):
  • Loading Dose: 150 mg/kg diluted in 200 mL of diluent* administered over 1 hr
  • Second Dose: 50 mg/kg diluted in 500 mL of diluent* administered over 4 hrs
  • Third Dose: 100 mg/kg diluted in 1,000 mL of diluent administered over 16 hrs

Patients Weighing More Than 100 kg

  • No specific studies have been conducted to evaluate the use of or necessity of dosing adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg. The dose of Acetylcysteine Injection recommended in these patients should be a loading dose of 15,000 mg infused over a period of one hour followed by a first maintenance dose of 5,000 mg over 4 hours and a second maintenance dose of 10,000 mg over 16 hours (Table 3).

Continued Therapy beyond 21 Hours

  • While there is no clinical trial data to support infusions beyond 21 hours there is literature that supports continued infusion of acetylcysteine in some rare instances. In cases of suspected massive overdose, or with concomitant ingestion of other substances, or in patients with preexisting liver disease, the absorption and/or the half-life of acetaminophen may be prolonged, in such cases consideration should be given to the need for continued infusion of N-acetylcysteine beyond 21 hours. Acetaminophen levels and ALT/AST & INR should be checked before the end of the 21-hour infusion. If acetaminophen levels are still detectable, or in cases in which the ALT/AST are still increasing or the INR remains elevated, the infusion should be continued, and the treating physician should contact a US regional poison center at 1-800-222-1222, or alternatively, a “special health professional assistance line for acetaminophen overdose” at 1-800-525-6115 for assistance with dosing recommendations.

Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction

  • The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction. To avoid fluid overload, the volume of diluent should be reduced as clinically needed. If the volume of the infusion is not adjusted, fluid overload can occur, potentially resulting in hyponatremia, seizure and death.
  • As Acetylcysteine Injection is hyperosmolar (2600 mOsmol/L), caution is advised when the diluent volume is decreased as the hyperosmolarity of the solution is increased. See Table 4 below for examples.
  • Single dose vial, preservative-free, discard unused portion. If vial was previously opened, do not use for intravenous administration.
  • Stability studies indicate that the diluted solution is stable for 24 hours at controlled room temperature.
  • Note: The color of Acetylcysteine Injection may turn from essentially colorless to a slight pink or purple once the stopper is punctured. The color change does not affect the quality of the product.

Renal Impairment

  • No data are available to determine if a dose adjustment in patients with moderate or severe renal impairment is required.

Hepatic Impairment

  • Although there was a threefold increase in acetylcysteine plasma concentrations in patients with hepatic cirrhosis, no data are available to determine if a dose adjustment in these patients is required. The published medical literature does not indicate that the dose of acetylcysteine in patients with hepatic impairment should be reduced.

DOSAGE FORMS & STRENGTHS

  • Each single dose vial contains 6g/30mL (200 mg/mL) of Acetylcysteine. Acetylcysteine Injection is sterile and can be used for intravenous administration.
Administration of anesthesia for procedure
  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
Atelectasis, Due to mucous obstruction
  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter
Bronchopulmonary disease, acute
  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Complication of surgical procedure - Respiratory complication

  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Cystic fibrosis, Pulmonary complications; Adjunct

  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Diagnostic procedure on lower respiratory tract

  • Dosing Information
  • Diagnostic bronchial studies: 1 to 2 mL of the 20% solution or 2 to 4 mL of the 10% solution 2 or 3 times prior to the procedure by nebulization or by instillation intratracheally

Disease of respiratory system, chronic

  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Disease of respiratory system, chronic: direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Disease of respiratory system, chronic: percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Disease of respiratory system, chronic: intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Tracheostomy care

  • Dosing Information
  • Nebulization into tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

  • There is limited information regarding Off-Label Guideline-Supported Use of Acetylcysteine (injection) in adult patients.

Non–Guideline-Supported Use

  • There is limited information regarding Off-Label Non–Guideline-Supported Use of Acetylcysteine (injection) in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Acetaminophen overdose
  • Dosing Information
  • Oral: initial, 140 mg/kg ORALLY, then 70 mg/kg every 4 hours for 17 doses starting 4 hours after loading dose
  • IV: body weight 5 to 20 kg: loading dose, 150 mg/kg in 3 mL/kg of compatible solution (D5W, 0.45%NaCl, or sterile water for injection) IV over 60 minutes, then 50 mg/kg in 7 mL/kg of compatible solution IV over 4 hours, followed by 100 mg/kg in 14 mL/kg of compatible solution IV over 16 hours; may continue beyond 21 hours if clinically indicated; adjust the total volume administered for patients requiring fluid restriction as clinically necessary
  • IV: body weight 21 kg to 40 kg: loading dose, 150 mg/kg in 100 mL of compatible solution (D5W, 0.45%NaCl, or sterile water for injection) IV over 60 minutes, then 50 mg/kg in 250 mL of compatible solution IV over 4 hours, followed by 100 mg/kg in 500 mL of compatible solution IV over 16 hours; may continue beyond 21 hours if clinically indicated; adjust the total volume administered for patients less than 40 kg or requiring fluid restriction as clinically necessary
  • IV: body weight 41 to 100 kg, loading dose, 150 mg/kg in 200 mL of compatible solution (D5W, 0.45%NaCl, or sterile water for injection) IV over 60 minutes, then 50 mg/kg in 500 mL of compatible solution IV over 4 hours, followed by 100 mg/kg in 1000 mL of solution IV over 16 hours; may continue beyond 21 hours if clinically indicated; adjust the total volume administered for patients requiring fluid restriction as clinically necessary [3]
  • IV: body weight over 100 kg, loading dose, 15,000 mg in 200 mL of compatible solution (D5W, 0.45%NaCl, or sterile water for injection) IV over 60 minutes, then 5000 mg in 500 mL of compatible solution IV over 4 hours, followed by 10,000 mg in 1000 mL of solution IV over 16 hours; may continue beyond 21 hours if clinically indicated; adjust the total volume administered for patients requiring fluid restriction as clinically necessary
Administration of anesthesia for procedure
  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Atelectasis, Due to mucous obstruction

  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Bronchopulmonary disease, acute

  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Complication of surgical procedure - Respiratory complication

  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Cystic fibrosis, Pulmonary complications; Adjunct

  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Diagnostic procedure on lower respiratory tract

  • Dosing Information
  • Diagnostic bronchial studies: 1 to 2 mL of the 20% solution or 2 to 4 mL of the 10% solution 2 or 3 times prior to the procedure by nebulization or by instillation intratracheally

Disease of respiratory system, chronic

  • Dosing Information
  • Nebulization into a face mask, mouth piece, or tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Nebulization into a tent or croupette: individualize treatment; use the volume of the 10% or 20% solution that will maintain a very heavy mist in the tent or croupette
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Tracheostomy care

  • Dosing Information
  • Nebulization into tracheostomy: 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution every 2 to 6 hours; usual dose is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 4 times daily
  • Direct instillation into tracheostomy: 1 to 2 mL of a 10% or 20% solution may be given as often as every hour; usual dose is 1 to 2 mL of a 10% or 20% solution every 1 to 4 hours
  • Percutaneous intratracheal catheter: 1 to 2 mL of 20% solution or 2 to 4 mL of 10% solution every 1 to 4 hours via a syringe attached to the catheter
  • Intratracheal catheter into particular bronchopulmonary tree segment: 2 to 5 mL of the 20% solution via a syringe attached to the catheter

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

  • There is limited information regarding Off-Label Guideline-Supported Use of Acetylcysteine (injection) in pediatric patients.

Non–Guideline-Supported Use

  • There is limited information regarding Off-Label Non–Guideline-Supported Use of Acetylcysteine (injection) in pediatric patients.

Contraindications

  • Acetylcysteine Injection is contraindicated in patients with previous anaphylactoid reactions to acetylcysteine.

Warnings

Anaphylactoid Reactions

  • Serious anaphylactoid reactions, including death in a patient with asthma, have been reported in patients administered acetylcysteine intravenously.
  • Acute flushing and erythema of the skin may occur in patients receiving acetylcysteine intravenously. These reactions usually occur 30 to 60 minutes after initiating the infusion and often resolve spontaneously despite continued infusion of acetylcysteine. Anaphylactoid reactions (defined as the occurrence of an acute hypersensitivity reaction during acetylcysteine administration including rash, hypotension, wheezing, and/or shortness of breath) have been observed in patients receiving intravenous acetylcysteine for acetaminophen overdose and occurred soon after initiation of the infusion.If a reaction to acetylcysteine involves more than simply flushing and erythema of the skin, it should be treated as an anaphylactoid reaction. This usually entails administering antihistaminic drugs and in severe cases may require administration of epinephrine. In addition, the acetylcysteine infusion may be interrupted until treatment of the anaphylactoid symptoms has been initiated and then carefully restarted. If the anaphylactoid reaction returns upon reinitiation of treatment or increases in severity, intravenous acetylcysteine should be discontinued and alternative patient management should be considered.

Monitoring patients with asthma

  • Acetylcysteine Injection should be used with caution in patients with asthma, or where there is a history of bronchospasm.

Volume Adjustment: Patients less than 40 kg and Requiring Fluid Restriction

  • The total volume administered should be adjusted for patients less than 40 kg and for those requiring fluid restriction. To avoid fluid overload, the volume of diluent should be reduced as needed. If volume is not adjusted fluid overload can occur, potentially resulting in hyponatremia, seizure and death.
  • For specific treatment information regarding the clinical management of acetaminophen overdose, please contact your regional poison center at 1-800-222-1222, or alternatively, a special health professional assistance line for acetaminophen overdose at 1-800-525-6115.
  • After proper administration of acetylcysteine, an increased volume of liquified bronchial secretions may occur. When cough is inadequate, the open airway must be maintained by mechanical suction if necessary. When there is a mechanical block due to foreign body or local accumulation, the airway should be cleared by endotracheal aspiration, with or without bronchoscopy. Asthmatics under treatment with acetylcysteine should be watched carefully. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, this medication should be discontinued immediately.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Acetylcysteine (injection) Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Acetylcysteine (injection) Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Acetylcysteine (injection) Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Acetylcysteine (injection) in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Acetylcysteine (injection) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Acetylcysteine (injection) during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Acetylcysteine (injection) in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Acetylcysteine (injection) in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Acetylcysteine (injection) in geriatric settings.

Gender

There is no FDA guidance on the use of Acetylcysteine (injection) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Acetylcysteine (injection) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Acetylcysteine (injection) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Acetylcysteine (injection) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Acetylcysteine (injection) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Acetylcysteine (injection) in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Acetylcysteine (injection) Administration in the drug label.

Monitoring

There is limited information regarding Acetylcysteine (injection) Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Acetylcysteine (injection) and IV administrations.

Overdosage

There is limited information regarding Acetylcysteine (injection) overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

Template:Px
Template:Px
Acetylcysteine (injection)
Systematic (IUPAC) name
(2R)-2-acetamido-3-sulfanylpropanoic acid[1]
Identifiers
CAS number 7218-04-4
ATC code R05CB01 S01XA08 (WHO) V03AB23 (WHO)
PubChem 581
DrugBank DB06151
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 163.195
SMILES eMolecules & PubChem
Physical data
Melt. point 106 °C (223 °F)
Boiling point 108 °C (226 °F)
Solubility in water 200 mg/mL (20 °C)
Pharmacokinetic data
Bioavailability 4-10% (Oral)[2][3][4][5][6]
Protein binding 80-83%[2][3][4][5][6]
Metabolism Hepatic[2][3][4][5][6]
Half life 5.6 hours[2][3][4][5][6]
Excretion Renal (22%), faecal (3%)[2][3][4][5][6]
Therapeutic considerations
Licence data

US

Pregnancy cat.

B2(AU) B(US)

Legal status

Pharmacy Only (S2)(AU) [[Prescription drug|Template:Unicode-only]](US)

Routes Oral, injection, inhalation

Mechanism of Action

There is limited information regarding Acetylcysteine (injection) Mechanism of Action in the drug label.

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Acetylcysteine (injection) Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Acetylcysteine (injection) Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Acetylcysteine (injection) Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Acetylcysteine (injection) Clinical Studies in the drug label.

How Supplied

There is limited information regarding Acetylcysteine (injection) How Supplied in the drug label.

Storage

There is limited information regarding Acetylcysteine (injection) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

This image is provided by the National Library of Medicine.
This image is provided by the National Library of Medicine.

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Patient Counseling Information

There is limited information regarding Acetylcysteine (injection) Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Acetylcysteine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • ACETYLCYSTEINE®[7]

Look-Alike Drug Names

There is limited information regarding Acetylcysteine (injection) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ "L-Cysteine, N-acetyl- - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 25 March 2005. Identification. Retrieved 9 January 2012.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 "ACETYLCYSTEINE solution [Fresenius Kabi USA, LLC]". DailyMed. Fresenius Kabi USA, LLC. September 2013. Retrieved 8 November 2013.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 "ACETADOTE (acetylcysteine) injection, solution [Cumberland Pharmaceuticals Inc.]". DailyMed. Cumberland Pharmaceuticals Inc. June 2013. Retrieved 8 November 2013.
  4. ↑ 4.0 4.1 4.2 4.3 4.4 Acetylcysteine. Martindale: The Complete Drug Reference. The Royal Pharmaceutical Society of Great Britain. 16 November 2012. Retrieved 8 November 2013.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 "PRODUCT INFORMATION ACETADOTE® CONCENTRATED INJECTION" (PDF). TGA eBusiness Services. Phebra Pty Ltd. 16 January 2013. Retrieved 8 November 2013.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 Borgström L, Kågedal B, Paulsen O (1986). "Pharmacokinetics of N-acetylcysteine in man". Eur. J. Clin. Pharmacol. 31 (2): 217–22. doi:10.1007/BF00606662. PMID 3803419.
  7. ↑ "ACETYLCYSTEINE- acetylcysteine injection".
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