ACETADOTE
Generic: ACETYLCYSTEINE
Basic Information
Manufacturer
Cumberland Pharmaceuticals Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
472f158a-5ab9-4308-8e49-1116e6ea3d39
Indications & Usage
1 INDICATIONS AND USAGE ACETADOTE is indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in adults and pediatric patients who weigh 5 kg or greater with acute ingestion or from repeated supratherapeutic ingestion (RSI).
ACETADOTE is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in adults and pediatric patients who weigh 5 kg or greater with acute ingestion or from repeated supratherapeutic ingestion (RSI) ( 1 ).
ACETADOTE is an antidote for acetaminophen overdose indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of acetaminophen in adults and pediatric patients who weigh 5 kg or greater with acute ingestion or from repeated supratherapeutic ingestion (RSI) ( 1 ).
Adverse Reactions
6 ADVERSE REACTIONS Most common adverse reactions (> 2%) are rash, urticaria/facial flushing and pruritus ( 6.1 ).
To report SUSPECTED ADVERSE REACTIONS, contact Cumberland Pharmaceuticals Inc.
at 1-877-484-2700 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Studies Experience The following clinically significant adverse reactions are described elsewhere in labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Fluid Overload [see Warnings and Precautions ( 5.2 )] Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the literature, the most frequently reported adverse reactions attributed to intravenous acetylcysteine administration were rash, urticaria and pruritus.
The frequency of adverse reactions has been reported to be between 0.2% and 21%, and they most commonly occur during the initial loading dose of acetylcysteine.
Loading Dose/Infusion Rate Study In a randomized, open-label, multi-center clinical study conducted in Australia in patients with acetaminophen poisoning, the rates of hypersensitivity reactions between a 15-minute and 60-minute intravenous infusion for the 150 mg/kg loading dose of acetylcysteine were compared.
The incidence of drug-related adverse reactions occurring within the first 2 hours following acetylcysteine administration is presented in Table 4 .
Overall, 17% of patients developed an acute hypersensitivity reaction (18% in the 15-minute infusion group; 14% in the 60-minute infusion group) [see Warnings and Precautions ( 5.1 ), Clinical Studies ( 14 )] .
Table 4.
Incidence of Drug-Related Adverse Reactions Occurring Within the First 2 Hours Following Study Drug Administration by Preferred Term: Loading Dose/Infusion Rate Study Treatment Group 15-minutes 60-minutes Unkn= Unknown; NOS= not otherwise specified Number of Patients n=109 n=71 Cardiac disorders 5 (5%) 2 (3%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Tachycardia NOS 4 (4%) 1 (1%) 2 (3%) Gastrointestinal disorders 16 (15%) 7 (10%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Nausea 1 (1%) 6 (6%) 1 (1%) 1 (1%) Vomiting NOS 2 (2%) 11 (10%) 2 (3%) 4 (6%) Immune System Disorders 20 (18%) 10 (14%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Hypersensitivity reaction 2 (2%) 6 (6%) 11 (10%) 1 (1%) 4 (6%) 5 (7%) 1 (1%) Respiratory, thoracic and mediastinal disorders 2 (2%) 2 (3%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Pharyngitis 1 (1%) Rhinorrhea 1 (1%) Rhonchi 1 (1%) Throat tightness 1 (1%) Skin & subcutaneous tissue disorders 6 (6%) 5 (7%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Pruritus 1 (1%) 2 (3%) Rash NOS 3 (3%) 2 (2%) 3 (4%) Vascular disorders 2 (2%) 3 (4%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Flushing 1 (1%) 1 (1%) 2 (3%) 1 (1%) Safety Study A large multi-center study was performed in Canada where data were collected from patients who were treated with intravenous acetylcysteine for acetaminophen overdose between 1980 and 2005.
This study evaluated 4709 adult cases and 1905 pediatric cases.
The incidence of hypersensitivity reactions in adult (overall incidence 8%) and pediatric (overall incidence 10%) patients is presented in Table 5 and Table 6 .
Table 5.
Distribution of reported hypersensitivity reactions in adult patients receiving intravenous acetylcysteine Reaction Incidence (%) n=4709 *Respiratory symptoms are defined as presence of any of the following: cough, wheezing, stridor, shortness of breath, chest tightness, respiratory distress, or bronchospasm.
Urticaria/Facial Flushing 6.1% Pruritus 4.3% Respiratory Symptoms* 1.9% Edema 1.6% Hypotension 0.1% Anaphylaxis 0.1% Table 6.
Distribution of reported hypersensitivity reactions in pediatric patients receiving intravenous acetylcysteine Reaction Incidence (%) n=1905 *Respiratory symptoms are defined as presence of any of the following: cough, wheezing, stridor, shortness of breath, chest tightness, respiratory distress, or bronchospasm.
Urticaria/Facial Flushing 7.6% Pruritus 4.1% Respiratory Symptoms* 2.2% Edema 1.2% Anaphylaxis 0.2% Hypotension 0.1% 6.2 Postmarketing Experience Adverse Reactions from Observational Studies Observational studies from published literature have described rates of hypersensitivity reactions identified by retrospective chart review in subjects receiving the two-bag regimen after adoption of this regimen as institutional policy in three non-US settings and one US setting compared to a historical control group that received the three-bag regimen.
Table 7 displays the incidence of hypersensitivity reactions in patients who received two-bag or three-bag regimens of intravenous acetylcysteine admitted between 2009 to 2020.
Table 7.
Incidence of Hypersensitivity Reactions in Patients who Received Two-bag or Three-bag Regimens of Intravenous Acetylcysteine in Published Literature Study Hypersensitivity Reactions in Patients Receiving Two-Bag Regimen Hypersensitivity Reactions in Patients Receiving Three-Bag Regimen Study 1 (Three Danish hospitals) 4% (19/507) 16% (47/292) Study 2 (Four Australian hospitals) 5% (8/163) 14% (45/313) Study 3 (Nine Australian hospitals) 1% (17/1300) 7% (65/911) Study 4 (One US hospital) 19% (18/93) 23% (34/150) Adverse Reactions from Postmarketing Spontaneous Reports The following adverse reactions have been identified during post-approval use of ACETADOTE.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune system disorders: fatal anaphylaxis
To report SUSPECTED ADVERSE REACTIONS, contact Cumberland Pharmaceuticals Inc.
at 1-877-484-2700 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Studies Experience The following clinically significant adverse reactions are described elsewhere in labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Fluid Overload [see Warnings and Precautions ( 5.2 )] Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In the literature, the most frequently reported adverse reactions attributed to intravenous acetylcysteine administration were rash, urticaria and pruritus.
The frequency of adverse reactions has been reported to be between 0.2% and 21%, and they most commonly occur during the initial loading dose of acetylcysteine.
Loading Dose/Infusion Rate Study In a randomized, open-label, multi-center clinical study conducted in Australia in patients with acetaminophen poisoning, the rates of hypersensitivity reactions between a 15-minute and 60-minute intravenous infusion for the 150 mg/kg loading dose of acetylcysteine were compared.
The incidence of drug-related adverse reactions occurring within the first 2 hours following acetylcysteine administration is presented in Table 4 .
Overall, 17% of patients developed an acute hypersensitivity reaction (18% in the 15-minute infusion group; 14% in the 60-minute infusion group) [see Warnings and Precautions ( 5.1 ), Clinical Studies ( 14 )] .
Table 4.
Incidence of Drug-Related Adverse Reactions Occurring Within the First 2 Hours Following Study Drug Administration by Preferred Term: Loading Dose/Infusion Rate Study Treatment Group 15-minutes 60-minutes Unkn= Unknown; NOS= not otherwise specified Number of Patients n=109 n=71 Cardiac disorders 5 (5%) 2 (3%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Tachycardia NOS 4 (4%) 1 (1%) 2 (3%) Gastrointestinal disorders 16 (15%) 7 (10%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Nausea 1 (1%) 6 (6%) 1 (1%) 1 (1%) Vomiting NOS 2 (2%) 11 (10%) 2 (3%) 4 (6%) Immune System Disorders 20 (18%) 10 (14%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Hypersensitivity reaction 2 (2%) 6 (6%) 11 (10%) 1 (1%) 4 (6%) 5 (7%) 1 (1%) Respiratory, thoracic and mediastinal disorders 2 (2%) 2 (3%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Pharyngitis 1 (1%) Rhinorrhea 1 (1%) Rhonchi 1 (1%) Throat tightness 1 (1%) Skin & subcutaneous tissue disorders 6 (6%) 5 (7%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Pruritus 1 (1%) 2 (3%) Rash NOS 3 (3%) 2 (2%) 3 (4%) Vascular disorders 2 (2%) 3 (4%) Severity: Unkn Mild Moderate Severe Unkn Mild Moderate Severe Flushing 1 (1%) 1 (1%) 2 (3%) 1 (1%) Safety Study A large multi-center study was performed in Canada where data were collected from patients who were treated with intravenous acetylcysteine for acetaminophen overdose between 1980 and 2005.
This study evaluated 4709 adult cases and 1905 pediatric cases.
The incidence of hypersensitivity reactions in adult (overall incidence 8%) and pediatric (overall incidence 10%) patients is presented in Table 5 and Table 6 .
Table 5.
Distribution of reported hypersensitivity reactions in adult patients receiving intravenous acetylcysteine Reaction Incidence (%) n=4709 *Respiratory symptoms are defined as presence of any of the following: cough, wheezing, stridor, shortness of breath, chest tightness, respiratory distress, or bronchospasm.
Urticaria/Facial Flushing 6.1% Pruritus 4.3% Respiratory Symptoms* 1.9% Edema 1.6% Hypotension 0.1% Anaphylaxis 0.1% Table 6.
Distribution of reported hypersensitivity reactions in pediatric patients receiving intravenous acetylcysteine Reaction Incidence (%) n=1905 *Respiratory symptoms are defined as presence of any of the following: cough, wheezing, stridor, shortness of breath, chest tightness, respiratory distress, or bronchospasm.
Urticaria/Facial Flushing 7.6% Pruritus 4.1% Respiratory Symptoms* 2.2% Edema 1.2% Anaphylaxis 0.2% Hypotension 0.1% 6.2 Postmarketing Experience Adverse Reactions from Observational Studies Observational studies from published literature have described rates of hypersensitivity reactions identified by retrospective chart review in subjects receiving the two-bag regimen after adoption of this regimen as institutional policy in three non-US settings and one US setting compared to a historical control group that received the three-bag regimen.
Table 7 displays the incidence of hypersensitivity reactions in patients who received two-bag or three-bag regimens of intravenous acetylcysteine admitted between 2009 to 2020.
Table 7.
Incidence of Hypersensitivity Reactions in Patients who Received Two-bag or Three-bag Regimens of Intravenous Acetylcysteine in Published Literature Study Hypersensitivity Reactions in Patients Receiving Two-Bag Regimen Hypersensitivity Reactions in Patients Receiving Three-Bag Regimen Study 1 (Three Danish hospitals) 4% (19/507) 16% (47/292) Study 2 (Four Australian hospitals) 5% (8/163) 14% (45/313) Study 3 (Nine Australian hospitals) 1% (17/1300) 7% (65/911) Study 4 (One US hospital) 19% (18/93) 23% (34/150) Adverse Reactions from Postmarketing Spontaneous Reports The following adverse reactions have been identified during post-approval use of ACETADOTE.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune system disorders: fatal anaphylaxis