Acetadote Dosage

Generic name: Acetylcysteine 200mg in 1mL
Dosage form: injection, solution
Drug class: Antidotes

Medically reviewed by Drugs.com. Last updated on Nov 30, 2024.

Pre-Treatment Assessment and Testing Following Acute Acetaminophen Ingestion

Prior to initiating treatment with ACETADOTE, decide whether the three-bag or two-bag regimen will be used.

The following recommendations are related to acute acetaminophen ingestion. For recommendations related to repeated supratherapeutic exposure.

Assess the history and timing of acetaminophen ingestion as an overdose.
- The reported history of the quantity of acetaminophen ingested as an overdose is often inaccurate and is not a reliable guide to therapy.
Obtain the following laboratory tests to monitor hepatic and renal function and electrolyte and fluid balance: aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, international normalized ratio (INR), creatinine, blood urea nitrogen (BUN), blood glucose, and electrolytes.
Obtain a plasma or serum sample to assay for acetaminophen concentration at least 4 hours after ingestion. Acetaminophen concentrations obtained earlier than 4 hours post-ingestion may be misleading as they may not represent maximum acetaminophen concentrations.
If the time of acute acetaminophen ingestion is unknown:
- Administer a loading dose of ACETADOTE immediately.
- Obtain an acetaminophen concentration to determine need for continued treatment.
If the acetaminophen concentration cannot be obtained (or is unavailable or uninterpretable) within the 8-hour time interval after acetaminophen ingestion or there is clinical evidence of acetaminophen toxicity:
- Administer a loading dose of ACETADOTE immediately and continue treatment for a total of two doses over 20 hours or three doses over 21 hours.
If the patient presents more than 8 hours after ingestion and the time of acute acetaminophen ingestion is known:
- Administer a loading dose of ACETADOTE immediately
- Obtain an acetaminophen concentration to determine need for continued treatment.
If the patient presents less than 8 hours after ingestion and the time of acute acetaminophen ingestion is known and the acetaminophen concentration is known:
- Use the revised Rumack-Matthew nomogram (Figure 1) to determine whether or not to initiate treatment with ACETADOTE.

Nomogram for Estimating Potential for Hepatoxicity from Acute Acetaminophen Ingestion and Need for ACETADOTE Treatment

ACETADOTE is an antidote for acetaminophen overdose. The critical ingestion-treatment interval for maximal protection against severe hepatic injury is between 0 and 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.

If the timing of the acute acetaminophen ingestion is known and the results of the acetaminophen assay are available within 8 hours:

Refer to the revised Rumack-Matthew nomogram (see Figure 1) to determine whether or not to initiate treatment with ACETADOTE.
Initiation of ACETADOTE depends on the plasma or serum acetaminophen concentration and also the clinical presentation of the patient.

The nomogram may underestimate the hepatotoxicity risk in patients with chronic alcoholism, malnutrition, or CYP2E1 enzyme inducing drugs (e.g., isoniazid), and consideration should be given to treating these patients even if the acetaminophen concentrations are in the nontoxic range.

Loading dose

For patients whose acetaminophen concentrations are at or above the “possible” treatment line (dotted line in nomogram):

Administer a loading dose of ACETADOTE.

For patients with an acute overdose from an extended-release acetaminophen, if the acetaminophen concentration at 4 hours post ingestion is below the possible treatment line then obtain a second sample for acetaminophen concentration 8 to 10 hours after the acute ingestion. If the second value is at or above the “possible” treatment line (dotted line in nomogram):

Administer a loading dose of ACETADOTE.

For patients whose values are below the “possible” treatment line, but time of ingestion was unknown or sample was obtained less than 4 hours after ingestion:

Administer a loading dose of ACETADOTE.

For patients whose values are below the “possible” treatment line and time of ingestion is known and the sample was obtained more than 4 hours after ingestion, do not administer ACETADOTE because there is minimal risk of hepatotoxicity.

Figure 1. Revised Rumack-Matthew Nomogram for Estimating Potential for Hepatoxicity for Acetaminophen Poisioning – Plasma or Serum Acetaminophen Concentration versus Time (hours) Post-acetaminophen Ingestion

(Dart et al., JAMA Network Open 2023; 6(89): e2337926)

Maintenance Dose

Determine the need for continued treatment with ACETADOTE after the loading dose. Choose ONE of the following based on the acetaminophen concentration:

The acetaminophen concentration is above the possible treatment line according to the nomogram (see Figure 1):

Continue ACETADOTE treatment with the maintenance dose for a total of either two or three separate doses over an infusion time of 20 or 21 hours, respectively.
Monitor hepatic and renal function and electrolytes throughout treatment.

The acetaminophen concentration could not be obtained:

Continue ACETADOTE treatment with the maintenance dose for a total of either two or three separate doses over an infusion time of 20 or 21 hours, respectively.
Monitor hepatic and renal function and electrolytes throughout treatment.

For patients whose acetaminophen concentration is below the “possible” treatment line (see Figure 1) and time of ingestion is known and the sample was obtained more than 4 hours after ingestion:

Discontinue ACETADOTE.

The acetaminophen concentration was in the non-toxic range, but time of ingestion was unknown or less than 4 hours:

Obtain a second sample for acetaminophen concentration and consider the patient's clinical status to decide whether or not to continue ACETADOTE treatment.
If there is any uncertainty as to patient's risk of developing hepatotoxicity, it is recommended to administer a complete treatment course.

Continued Therapy After Completion of Loading and Maintenance Doses

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 treatment with ACETADOTE beyond the total 300 mg/kg dose.

Acetaminophen levels and ALT/AST and INR should be checked after the last maintenance dose. If acetaminophen levels are still detectable, or if the ALT/AST are still increasing or the INR remains elevated; dosing should be continued and the treating physician should contact a US regional poison center at 1-800-222-1222, alternatively, a “special health professional assistance line for acetaminophen overdose” at 1-800-525-6115 for assistance with dosing recommendations, or 1-877-484-2700 for additional information.

Preparation and Storage of ACETADOTE Diluted Solution Prior to Administration

Refer to Table 2 and Table 3 to calculate the dose (mg) based on the patient's weight in kg; multiple vials of ACETADOTE may be required. Discard any unused portion left in the vial.

Because ACETADOTE is hyperosmolar (2,600 mOsmol/L), ACETADOTE must be diluted in the recommended volume of sterile water for injection, 0.45% sodium chloride injection (1/2 normal saline), or 5% dextrose in water prior to intravenous administration. The total injection volume will vary based on the patient's weight and chosen dosage regimen (i.e., three-bag or two-bag).

The choice of diluent should be based on the individual patient's clinical status, concurrent medical conditions, and institutional protocols. The treating clinician should assess each case individually and consult with their pharmacy if there are any concerns about the appropriate diluent choice. In general, 0.45% normal saline is the preferred diluent because it provides a more consistent osmolarity profile, reduces the amount of free water delivered to the patient, and better approximates physiologic fluids than 5% dextrose in water or sterile water for injection. However, consider 5% dextrose in water or sterile water for injection if sodium load is a concern for the patient.

Dilution of ACETADOTE in each of these three solutions results in different osmolarity of the acetylcysteine solution for intravenous administration (see Table 1 for examples of different osmolarity of the solution depending on the type of solution and the ACETADOTE concentration).

Table 1. Examples of Acetylcysteine Concentration and Osmolarity in Three Solutions
* Adjust osmolarity to a physiologically safe level (generally not less than 150 mOsmol/L in pediatric patients).
Acetylcysteine Concentration	Osmolarity
Acetylcysteine Concentration	Sterile Water for Injection	0.45% Sodium Chloride Injection	5% Dextrose in Water (D5W)
4 mg/mL (lowest concentration 3-bag protocol)	52 mOsmol/L*	194 mOsmol/L	311 mOsmol/L
54.5 mg/mL (highest concentration 3-bag protocol)	744 mOsmol/L	855 mOsmol/L	957 mOsmol/L
7.9 mg/mL (lowest concentration 2-bag protocol)	105 mOsmol/L	241 mOsmol/L	360 mOsmol/L
18.2 mg/mL (highest concentration 2-bag protocol)	239 mOsmol/L	368 mOsmol/L	487 mOsmol/L

The choice of diluent should be based on the individual patient's clinical status, concurrent medical conditions, and institutional protocols. The treating clinician should assess each case individually and consult with their pharmacy if there are any concerns about the appropriate diluent choice. In general, 0.45% normal saline is the preferred diluent, as it provides a more consistent osmolarity profile, reduces the amount of free water delivered to the patient, and better approximates physiologic fluids than 5% dextrose in water or sterile water for injection.

Visually inspect for particular matter and discoloration prior to administration. The color of the diluted solution ranges from colorless to a slight pink or purple once the stopper is punctured (the color change does not affect the quality of the product). The diluted solution can be stored for 24 hours at room temperature. Discard the unused portion. If a vial was previously opened, do not use for intravenous administration.

General Considerations for Selecting the Three-Bag or Two-Bag Regimen

The total recommended dosage of ACETADOTE is 300 mg/kg given intravenously as either a three-bag regimen or a two-bag regimen.

It is not known whether the two-bag regimen is comparable to the three-bag regimen for efficacy in preventing hepatotoxicity.

There are insufficient data to recommend use of the two-bag regimen in patients 40 kg or less; these patients should receive the three-bag regimen.

For patients weighing 41 kg or greater, the clinician should consider the following factors when deciding whether to select the three-bag or two-bag regimen:

The three-bag regimen administers more ACETADOTE in the first three hours and may be preferred for patients with early signs of severe liver injury or history of a large acetaminophen ingestion; however, there is the potential for a higher incidence of hypersensitivity reactions.
The two-bag regimen delivers a lower amount of ACETADOTE over the first three hours and may be associated with fewer hypersensitivity reactions than the three-bag regimen.

Recommended Dosage for Acute Acetaminophen Ingestion

ACETADOTE is for intravenous administration only.

The total recommended dosage of ACETADOTE is 300 mg/kg given intravenously as either a three-bag regimen administered as a loading, second, and third dose infused over a total of 21 hours or a two-bag regimen administered as a loading and second dose infused over a total of 20 hours.

For the recommended weight-based dosage and weight-based dilution in patients see Table 2 for the three-bag regimen (for patients 5 kg or greater) or Table 3 for the two-bag regimen (for patients 41 kg or greater).

Three-Bag Regimen

Table 2. Three-Bag Recommended ACETADOTE Dosage and Dilution for Patients 5 kg or greater
* Dilute ACETADOTE in one of the following three solutions: sterile water for injection, 0.45% sodium chloride injection, or 5% dextrose in water.
**Recommended dosing for those less than 5 kg has not been studied.
***No specific studies have been conducted to evaluate the necessity of dose adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg.
Body Weight	Bag 1 (Loading Dose)			Bag 2 (Second Dose)			Bag 3 (Third Dose)
Body Weight	Loading Dose	Diluent Volume*	Infusion time	Second Dose	Diluent Volume*	Infusion time	Third Dose	Diluent Volume*	Infusion time
5 kg** to 20 kg	150 mg/kg	3 mL/kg	Infused over 1 hour	50 mg/kg	7 mL/kg	Infused over 4 hours	100 mg/kg	14 mL/kg	Infused over 16 hours
21 kg to 40 kg	150 mg/kg	100 mL		50 mg/kg	250 mL		100 mg/kg	500 mL
41 kg to 99 kg	150 mg/kg	200 mL		50 mg/kg	500 mL		100 mg/kg	1,000 mL
100 kg or greater***	15,000 mg	200 mL		5,000 mg	500 mL		10,000 mg	1,000 mL

Two-Bag Regimen

Table 3. Alternative Regimen for Patients 41 kg or Greater: Two-Bag Recommended ACETADOTE Dosage and Dilution
*Dilute ACETADOTE in one of the following three solutions: sterile water for injection, 0.45% sodium chloride injection, or 5% dextrose in water.
**No specific studies have been conducted to evaluate the necessity of dose adjustments in patients weighing over 100 kg. Limited information is available regarding the dosing requirements of patients that weigh more than 100 kg.
Body Weight	Bag 1 (Loading Dose)			Bag 2 (Second Dose)
	Loading Dose	Diluent Volume*	Infusion time	Second Dose	Diluent Volume*	Infusion time
41 kg to 99 kg	200 mg/kg	1,000 mL	Infused over 4 hours	100 mg/kg	500 mL	Infused over 16 hours
100 kg or greater**	20,000 mg	1,000 mL		10,000 mg	500 mL

Recommendations for Repeated Supratherapeutic Acetaminophen Ingestion

Repeated supratherapeutic acetaminophen ingestion (RSI) is an ingestion of acetaminophen at dosages higher than those recommended for extended periods of time. The risk of hepatotoxicity and the recommendations for treatment of acute acetaminophen ingestion (i.e., the revised Rumack-Matthew nomogram) do not apply to patients with RSI. Therefore, obtain the following information to guide ACETADOTE treatment for RSI:

Acetaminophen serum or plasma concentrations. A reported history of the quantity of acetaminophen ingested is often inaccurate and is not a reliable guide to therapy.
Laboratory tests to monitor hepatic and renal function and electrolyte and fluid balance: AST, ALT, bilirubin, INR, creatinine, BUN, blood glucose, and electrolytes.

For specific ACETADOTE dosage and administration information in patients with RSI, consider contacting 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.