A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Acetadote Indications, Dosage, Storage, Stability - Acetylcysteine
Acetadote Indications, Dosage, Storage, Stability - Acetylcysteine
INDICATIONS AND USAGE
Acetadote, administered intravenously within 8 to 10 hours after ingestion of a potentially hepatotoxic quantity of acetaminophen, is indicated to prevent or lessen hepatic injury (see DOSAGE AND ADMINISTRATION and ACETAMINOPHEN ASSAYS - INTERPRETATIONAND METHODOLOGY sections).
DOSAGE AND ADMINISTRATION
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 l 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.
Acetadote 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 section). 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 acet-aminophen ingestion, Acetadote 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.
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 s between 0 - 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.
The following procedures are recommended for I.V. administration
Adults
Loading Dose: 150 mg/kg in 200 mL of 5% dextrose, infuse intravenously over 15 minutes. Maintenance Dose: 50 mg/kg In 500 mL of 5% dextrose, infuse intravenously over 4 hours followed by 100 mg/kg in 1000 mL of 5% dextrose, infuse intravenously over 16 hours.
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 5% dextrose should be reduced proportionately as needed (see PRECAUTIONS).
Single-dose vial, preservative-free, discard unused portion. If vial was previously opened, do not use for I.V. administration.
Stability
1. Stability studies indicate that the reconstituted solution is stable for 24 hours at controlled room temperature.
2. Acetadote is not compatible with rubber and metals, particularly iron, capper and nickel.
Figure 1 Acetadot e Treatment Flowchart
*Acetaminophen levels drawn less than 4 hours post-ingestion may be misleading.
**With the 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.
***Acetylcysteine 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.
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.
Preparation of Acetadote (Acetylcystelne) for Intravenous Administration
Intravenous administration requires dilution with 5% dextrose (see DOSAGE AND ADMINISTRATION).
Adults
Loading Dose: Dilute 150 mg/kg in 200 mL of 5% dextrose. First Maintenance Dose: 50 mg/kg in 500 mL of 5% dextrose. Second Maintenance Dose: 100 mg/kg in 1000 mL of 5% dextrose.
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 5% dextrose should be reduced proportionately as needed (see PRECAUTIONS).
Do not use previously opened vials for I.V. administration.
DOSAGE GUIDE AND PREPARATION
|
Table 3. Dosage Guide in Relation to Body Weight : Adult Patients
|
Body Weight |
FIRST150 mg/kg in 200 mL 5% Dextrose in 15min |
SECOND 50 mg/kg in 500 mL 5% Dextrose in 4 hours |
THIRD100 mg/kg in 1000 mL 5% Dextrose in 16 hours |
(kg) |
db) |
| |
|
Acetadote (mL) |
Acetadote (mL) |
Acetadote (mL) |
100 |
220 |
75 |
25 |
50 |
90 |
198 |
67.5 |
22.5 |
45 |
80 |
176 |
60 |
20 |
40 |
70 |
154 |
52.5 |
17.5 |
35 |
60 |
132 |
45 |
15 |
30 |
50 |
110 |
37.5 |
12.5 |
25 |
40 |
88 |
30 |
10 |
20 |
ACETAMINOPHEN ASSAYS-INTERPRETATION AND METHODOLOGY
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 OVERDOSEISPOTENTIALLYTOXIC.
Interpretation of Acetaminophen Assays
1 . When results of the plasma acetaminophen assay are available, refer to the nomogram below t o 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.
2. 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.
3. 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 (Figure 2) has been developed to estimate the probability that plasma levels in relation to intervals post ingestion will result in hepatotoxicity.
Figure 2 Rumack-Matthew Nomogram: Plasma or Serum Acetaminophen Concentration vs. Time Post Acetaminophen Ingestion
Acetaminophen Assay Methodology
Suitable assay procedures for measuring acetaminophen levels in plasma are listed below. These methods detect only parent acetaminophen and not conjugated acetaminophen.
Selected Techniques (nonlncluslve)
HPLC: Blair D and Rumack BH. Clin Chem 1977;23(4):743-5.
Howie D, Andriaenssens PI, and Prescott LF. J Pharm Pharmacol, 1977;29(4):235-7.
GC: Prescott LF. J Pharm Pharmacol, 1971;23(10):807-8.
Colorimetric: Glynn JP and Kendal SE. Lancet, 1975;1(May 17):1147-8.
HOW SUPPLIED
Acetadote (acetylcysteine) Injection is available as a 20% solution in 30 mL (200 mg/mL) single dose glass vials. Acetadote is sterile and can be used for I.V. administration. It is available as follows:
NDC 66220-107-30 30 mL vials, carton of 4
Store unopened vials at controlled room temperature, 20° to 25°C (68° to 77°F)
[See USP Controlled Room Temperature].
Manufactured for Cumberland Pharmaceuticals Inc. Nashville, TN 37203 Issued: March 2004 0484L101
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