1
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
CETYLEV
®
safely and effectively. See full prescribing information for
CETYLEV.
CETYLEV (acetylcysteine) effervescent tablets for oral solution
Initial U.S. Approval: 1963
----------------------------INDICATIONS AND USAGE---------------------------
CETYLEV is an antidote for acetaminophen overdose indicated to prevent or
lessen hepatic injury after ingestion of a potentially hepatotoxic quantity of
acetaminophen in patients with acute ingestion or from repeated
supratherapeutic ingestion. (1)
-----------------------DOSAGE AND ADMINISTRATION-----------------------
Pre-Treatment Assessment Following Acute Ingestion (2.1):
Obtain a plasma or serum sample to assay for acetaminophen concentration at
least 4 hours after ingestion.
If the time of acetaminophen ingestion is unknown:
o Administer a loading dose of CETYLEV immediately
o Obtain an acetaminophen concentration to determine the 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:
o Administer a loading dose of CETYLEV immediately and
continue treatment for a total of 17 doses.
If the patient presents more than 8 hours after ingestion and the time of
acute acetaminophen ingestion is known:
o Administer a loading dose of CETYLEV immediately
o Obtain 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:
o Use the Rumack-Matthew nomogram (Figure 1) to determine
whether or not to initiate treatment with CETYLEV (2.2)
Nomogram for Estimating Potential for Hepatotoxicity from Acute
Acetaminophen Ingestion (2.2):
See the Full Prescribing Information for instructions on how to use the
nomogram to determine the need for loading and maintenance dosing.
Recommended Adult and Pediatric Dosage (2.3):
CETYLEV is for oral administration only; not for nebulization or
intratracheal instillation
Loading dose: 140 mg/kg
Maintenance doses: 70 mg/kg repeated every 4 hours for a total of 17
doses.
See Full Prescribing Information for weight-based dosage and preparation
and administration instructions.
Repeated Supratherapeutic Acetaminophen Ingestion (2.4):
Obtain acetaminophen concentration and other laboratory tests to guide
treatment; Rumack-Matthew nomogram does not apply.
----------------------DOSAGE FORMS AND STRENGTHS---------------------
Effervescent tablets: 500 mg and 2.5 grams (3)
------------------------------CONTRAINDICATIONS-------------------------------
None (4)
------------------------WARNINGS AND PRECAUTIONS-----------------------
Hypersensitivity Reactions, Including Urticaria: Discontinue CETYLEV
unless deemed essential to patient management and the reactions can be
otherwise controlled (5.1)
Risk of Upper Gastrointestinal Hemorrhage: Consider the risk/benefit for
patients at risk of hemorrhage (e.g., those with esophageal varices, peptic
ulcers, etc.) versus the risk of developing hepatic toxicity, and treat with
CETYLEV accordingly.(5.2)
------------------------------ADVERSE REACTIONS-------------------------------
Most common adverse reactions are nausea and vomiting, other
gastrointestinal symptoms, and rash with or without fever. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Arbor
Pharmaceuticals LLC at 1- 866-516-4950 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and Patient
Information.
Revised: 04/2017
_____________________________________________________________________________________________________________________________________
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Pre-Treatment Assessment and Testing Following Acute
Acetaminophen Ingestion
2.2 Nomogram for Estimating Potential for Hepatotoxicity from Acute
Acetaminophen Ingestion and Need for CETYLEV Treatment
2.3 Recommended Dosage and Preparation and Administration
Instructions in Adults and Pediatrics for Acute Acetaminophen
Ingestion
2.4 Recommendations for Repeated Supratherapeutic Acetaminophen
Ingestion
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
5.2 Risk of Upper Gastrointestinal Hemorrhage
6 ADVERSE REACTIONS
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Patients Sensitive to High Sodium Intake
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.3 Pharmacokinetics
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
16 HOW SUPPLIED/STORAGE AND HANDLING
17 PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not
listed.
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
2
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
CETYLEV is indicated to prevent or lessen hepatic injury after ingestion of a potentially hepatotoxic quantity
of acetaminophen in patients with acute ingestion or from repeated supratherapeutic ingestion (RSI).
2 DOSAGE AND ADMINISTRATION
2.1 Pretreatment Assessment and Testing Following Acute Acetaminophen Ingestion
The following recommendations are related to acute acetaminophen ingestion. For recommendations related to
repeated supratherapeutic exposure see Dosage and Administration (2.4).
1. 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.
2. 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.
3. 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.
4. If the time of acute acetaminophen ingestion is unknown:
Administer a loading dose of CETYLEV immediately [see Dosage and Administration (2.3,
2.4)].
Obtain an acetaminophen concentration to determine need for continued treatment [see Dosage
and Administration (2.2)]
5. 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 CETYLEV immediately and continue treatment for a total of 17
doses [see Dosage and Administration (2.3)].
6. If the patient presents more than 8 hours after ingestion and the time of acute acetaminophen ingestion is
known:
Administer a loading dose of CETYLEV immediately [see Dosage and Administration (2.3)].
Obtain acetaminophen concentration to determine need for continued treatment [see Dosage and
Administration (2.2)].
7. 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 Rumack-Matthew nomogram (Figure 1) to determine whether or not to initiate treatment
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
3
with CETYLEV [see Dosage and Administration (2.2)]
2.2 Nomogram for Estimating Potential for Hepatotoxicity from Acute Acetaminophen Ingestion and
Need for CETYLEV Treatment
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 Rumack-Matthew nomogram (see Figure 1) to determine whether or not to initiate
treatment with CETYLEV.
Initiation of CETYLEV depends on the 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” toxicity line (dotted line in
nomogram):
Administer a loading dose of CETYLEV [see Dosage and Administration (2.3)].
For patients with an acute overdose due to an extended-release acetaminophen, if the acetaminophen
concentration at 4 hours post ingestion is below the possible toxicity 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” toxicity line (dotted line in nomogram):
Administer a loading dose of CETYLEV [see Dosage and Administration (2.3)].
For patients whose values are below the “possible” toxicity line, but time of ingestion was unknown or
sample was obtained less than 4 hours after ingestion:
Administer a loading dose of CETYLEV [see Dosage and Administration (2.3)].
For patients whose values are below the “possible” toxicity line and time of ingestion is known and the
sample was obtained more than 4 hours after ingestion, do not administer CETYLEV because there is
minimal risk of hepatotoxicity.
Figure 1 Rumack-Matthew Nomogram for Estimating Potential for
Hepatotoxicity from Acetaminophen Poisoning – Plasma or
Serum Acetaminophen Concentration versus Time (hours)
Post-acetaminophen Ingestion (Adapted from Rumack and
Matthew, Pediatrics 1975; 55:871−876.)
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
4
Maintenance Dose
Determine need for continued treatment with CETYLEV after the loading dose. Choose ONE of the following
based on the acetaminophen concentration:
The acetaminophen concentration is above the possible toxicity line according to the nomogram (see Figure 1):
Continue CETYLEV treatment with the maintenance dose for 17 doses [see Dosage and
Administration (2.3)].
Monitor hepatic and renal function and electrolytes throughout treatment.
The acetaminophen concentration could not be obtained:
Continue CETYLEV treatment with the maintenance dose for 17 doses [see Dosage and
Administration (2.3)].
Monitor hepatic and renal function and electrolytes throughout treatment.
For patients whose acetaminophen concentration is below the “possible” toxicity line (see Figure 1) and time
of ingestion is known and the sample was obtained more than 4 hours after ingestion:
Discontinue CETYLEV.
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
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
5
status to decide whether or not to continue CETYLEV treatment.
If there is any uncertainty as to patient’s risk of developing hepatotoxicity, it is recommended to
administer a complete treatment course under medical observation with appropriate monitoring..
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 CETYLEV beyond a total of 17
maintenance doses.
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;
the maintenance doses 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.
2.3 Recommended Dosage and Preparation and Administration Instructions in Adults and Pediatrics for
Acute Acetaminophen Ingestion
CETYLEV is for oral administration only; not for nebulization or intratracheal instillation.
After appropriate preparation and dilution, CETYLEV is interchangeable with 20% acetylcysteine
solution, when given at the same acetylcysteine dosage.
Adults and Pediatrics: The recommended loading dose of CETYLEV is 140 mg/kg. Administer a first
maintenance dose of 70 mg/kg 4 hours after the loading dose. Repeat 70 mg/kg maintenance dose every
4 hours for a total of 17 maintenance doses.
Preparation and Administration Instructions
Dissolve the appropriate number of 2.5 gram and/or 500 mg CETYLEV effervescent tablets in the
volume of water indicated in dosing tables and text below, based upon patient weight.
Once the tablets are dissolved, administer the oral solution immediately.
Solutions should be freshly prepared for each dose and utilized within 2 hours.
If the patient vomits an oral dose of CETYLEV within 1 hour of administration, repeat that dose.
If the patient is persistently unable to retain the orally administered acetylcysteine, CETYLEV may be
administered by nasoduodenal tube. An intravenous formulation of acetylcysteine may also be
considered.
Patients Weighing 20 kg and Greater
Tables 1 and 2 provide the weight-based loading and maintenance doses, respectively, of CETYLEV for
patients weighing 20 kg and greater. For patients weighing 20 to 59 kg dissolve CETYLEV tablets in 150 mL
of water. For patients weighing 60 kg and greater dissolve CETYLEV tablets in 300 mL of water.
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
6
Table 1: CETYLEV Loading Dose
Dissolve CETYLEV Tablets in 300 mL of Water
Body weight
(Kg)
Actual Acetylcysteine
Dose to be Administered
(grams)
Number of CETYLEV Tablets to
Dissolve in Water
2.5 gram tablets 500 mg tablets
100 or greater
15
6
0
90 to 99
14
5
3
80 to 89
13
5
1
70 to 79
11
4
2
60 to 69
10
4
0
Dissolve CETYLEV Tablets in 150 mL of Water
50 to 59
8
3
1
40 to 49
7
2
4
30 to 39
6
2
2
20 to 29
4
1
3
*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.
Table 2: CETYLEV Maintenance Dose
Dissolve CETYLEV Tablets in 300 mL of Water
Body weight
(Kg)
Actual Acetylcysteine
Dose to be
Administered
(grams)
Number of CETYLEV Tablets to
Dissolve in Water
2.5 gram tablets 500 mg tablets
100 or greater*
7.5
3
0
90 to 99
7
2
4
80 to 89
6.5
2
3
70 to 79
5.5
2
1
60 to 69
5
2
0
Dissolve CETYLEV Tablets in 150 mL of Water
50 to 59
4
1
3
40 to 49
3.5
1 2
30 to 39
3
1
1
20 to 29
2
0 4
*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.
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
7
Patients Weighing 1 to 19 kg
Dissolve two 2.5 gram CETYLEV effervescent tablets in 100 mL of water to create a 50 mg/mL solution.
Calculate the loading and maintenance doses using the patient’s kilogram weight:
Loading dose: Calculate the dose by multiplying the patient’s kilogram weight by 140 mg/kg and dividing by
the concentration of the solution (50 mg/mL). The result is the dose in mL for administration using an oral
syringe.
Maintenance dose: Calculate the dose by multiplying the patient’s kilogram weight by 70 mg/kg and dividing
by the concentration of the solution (50 mg/mL). The result is the dose in mL for administration using an oral
syringe.
2.4 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 Rumack-Matthew nomogram) do not apply to patients
with RSI. Therefore, obtain the following information to guide CETYLEV 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 CETYLEV 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.
3 DOSAGE FORMS AND STRENGTHS
CETYLEV effervescent tablets are supplied as white, round, flat tablets with a lemon mint flavor in the
following dosage strengths:
500 mg tablets debossed with “I” on one side.
2.5 gram tablets debossed with “O” on one side.
CETYLEV tablets contain the inactive ingredient sodium bicarbonate which may be clinically relevant in some
patients [see Use in Specific Populations (8.6), Description (11)].
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 Hypersensitivity Reactions
Hypersensitivity reactions, including generalized urticaria have been observed in patients receiving oral
acetylcysteine for acetaminophen overdose. If hypersensitivity reactions occur, CETYLEV should be
discontinued unless it is deemed essential for patient management and the reactions can be otherwise controlled.
5.2 Risk of Upper Gastrointestinal Hemorrhage
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
8
Occasionally severe and persistent vomiting occurs as a symptom of acute acetaminophen overdose. Treatment
with CETYLEV may aggravate the vomiting and increase the risk of upper gastrointestinal hemorrhage in at
risk patients (e.g., those with esophageal varices, peptic ulcers, etc.). Consider the risk/benefit for patients at
risk of hemorrhage versus the risk of developing hepatic toxicity, and treat with CETYLEV as needed.
6 ADVERSE REACTIONS
The following adverse reactions are described, or described in greater detail, in other sections of the labeling:
Hypersensitivity Reactions [see Warnings and Precautions (5.1)]
Risk for Upper Gastrointestinal Hemorrhage [see Warnings and Precautions (5.2)]
The most common adverse reactions have been identified from clinical studies or postmarketing reports of
acetylcysteine. 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.
The most common adverse reactions were nausea, vomiting, other gastrointestinal symptoms, and rash with or
without fever.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Limited published case reports and case series on acetylcysteine use during pregnancy are insufficient to inform
a drug-associated risk of birth defects and miscarriage. However, there are clinical considerations [see Clinical
Considerations]. In animal reproduction studies, no teratogenic effects were observed with oral administration
of acetylcysteine to pregnant rats and rabbits during organogenesis at doses up to 0.6 times the maximum
recommended human dose (based on body surface area) of about 560 mg/kg (total dose on first day of
treatment) [see Data].
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in
clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk
Acetaminophen and acetylcysteine cross the placenta. Delaying treatment in pregnant women with
acetaminophen overdose and potentially toxic acetaminophen plasma levels may increase the risk of maternal
and fetal morbidity and mortality.
Data
Animal Data
No teratogenic effects were observed in embryo-fetal development studies in rats at oral doses up to 2000
mg/kg/day (0.6 times the maximum recommended human dose based on body surface area) or in rabbits at oral
doses up to 1000 mg/kg/day (0.6 times the maximum recommended human dose based on body surface area)
administered during organogenesis.
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
9
8.2 Lactation
Risk Summary
There is no information regarding the presence of acetylcysteine in human milk, or the effects of acetylcysteine
on the breastfed infant or on milk production. The development and health benefits of breastfeeding should be
considered along with the mother’s clinical need for CETYLEV and any potential adverse effects on the
breastfed infant from CETYLEV or from the underlying maternal condition.
8.4 Pediatric Use
Pediatric approval, including dosing, is not based on adequate and well-controlled clinical studies. Pediatric
dosing recommendations are based on clinical experience [see Dosage and Administration (2.3)].
8.5 Geriatric Use
Clinical studies of acetylcysteine did not include sufficient numbers of subjects aged 65 and over to determine
whether they respond differently from younger subjects. Other reported clinical experience with acetylcysteine
has not identified differences in the responses between elderly and younger patients. In general, dose selection
for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater
frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
8.6 Patients Sensitive to High Sodium Intake
CETYLEV tablets contain sodium. Consider the total sodium content from dietary and non-dietary sources in
patients who may be sensitive to excess sodium intake, such as those with congestive heart failure,
hypertension, or renal impairment.
At the recommended dosage an average sized adult (60 kg) may receive a total of 7 grams of sodium (304.3
mEq) on the first day of treatment, 5.3 grams of sodium (230.4 mEq) on the second day of treatment, and 4.4
grams of sodium (191.3 mEq) on the third day of treatment.
If sodium intake is a concern, please refer to Table 3 for the amount of sodium in each tablet [see Description
(11)] and to Tables 1 and 2 for the recommended dosage in adults and pediatrics based on body weight in order
to calculate the amount of sodium administered to an individual patient [see Dosage and Administration (2.3)].
11 DESCRIPTION
Acetylcysteine is an antidote for the treatment of acetaminophen overdose. It is the N-acetyl derivative of the
naturally-occurring amino acid, cysteine. Acetylcysteine is a white crystalline powder that is freely soluble in
water, alcohol, practically insoluble in chloroform and in ether with the molecular formula C
5
H
9
NO
3
S, a
molecular weight of 163.2, and chemical name of N-acetyl-L-cysteine. Acetylcysteine has the following
structural formula:
CETYLEV (acetylcysteine) effervescent tablets for oral solution contain 500 mg or 2.5 grams of acetylcysteine.
The following are inactive ingredients: sodium bicarbonate, maltodextrin, lemon flavor, sucralose, peppermint
flavor, and edetate disodium.
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
10
The amount of sodium in each tablet of CETYLEV is shown in Table 3.
Table 3: Amount of Sodium Per CETYLEV Tablet
Tablet Strength
Sodium Bicarbonate (mg)*
Sodium (mg)
Sodium (mEq)
500 mg
320 mg
88 mg
3.8 mEq
2.5 grams
1600 mg
438 mg
19 mEq
*inactive ingredient
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose.
Acetaminophen doses of 150 mg/kg or greater have been associated with hepatotoxicity. Acetylcysteine
probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate
substrate for conjugation with, and thus detoxification of, the reactive metabolite of acetaminophen.
12.3 Pharmacokinetics
Absorption
After administration of a single oral dose of 11 grams of CETYLEV (dissolved in 300 mL of water) to 29
healthy adult subjects, the mean C
max
(CV%) was 26.5 (29) mcg/mL and mean (CV) AUC
inf
was 186 (29)
hr•mcg/mL. The median (range) time to reach C
max
(T
max
) was 2 (1 to 3.5) hours.
Distribution
The steady-state volume of distribution (V
d
) following administration of an intravenous dose of acetylcysteine
was 0.47 liter/kg. The protein binding for acetylcysteine ranges from 66% to 87 %.
Elimination
Metabolism
Acetylcysteine (i.e., N-acetylcysteine) undergoes extensive first pass metabolism and is postulated to form
cysteine and disulfides (N,N-diacetylcysteine and N-acetylcysteine). Cysteine is further metabolized to form
glutathione and other metabolites.
Excretion
After a single oral dose of [
35
S]-acetylcysteine 100 mg, between 13 to 38% of the total radioactivity
administered was recovered in urine within 24 hours. In a separate study, renal clearance was estimated to be
approximately 30% of total body clearance.
In healthy subjects given a single oral dose of 11 grams of CETYLEV, the mean (CV%) terminal plasma half-
life (T
1/2
) was 18.1 (22%) hours.
Specific Populations
Hepatic Impairment
Following a 600 mg intravenous dose of acetylcysteine to subjects with mild (Child Pugh Class A, n=1),
moderate (Child-Pugh Class B, n=4) or severe (Child-Pugh Class C; n=4) hepatic impairment and 6 healthy
matched controls, mean T
1/2
increased by 80%. Also, the mean CL decreased by 30% and the systemic
acetylcysteine exposure (mean AUC) increased 1.6-fold in subjects with hepatic impairment compared to
subjects with normal hepatic function. These changes are not considered to be clinically meaningful.
Renal Impairment
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
11
Hemodialysis may remove some of total acetylcysteine.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Carcinogenicity studies in laboratory animals have not been performed with acetylcysteine.
Mutagenesis
Acetylcysteine was negative in the Ames test.
Impairment of Fertility
In a fertility study of acetylcysteine in rats, intravenous administration of 1000 mg/kg/day (0.3 times the
recommended human oral dose based on body surface area) caused a profound reduction of fertility in females,
which was correlated with morphological changes in oocytes and severe impairment of implantation (18 of 20
mated females had no implantations). The reversibility of this effect was not evaluated. No effects on fertility
were observed in female rats at intravenous doses up to 300 mg/kg/day (0.1 times the recommended human oral
dose based on body surface area), or in male rats at intravenous doses up to 1000 mg/kg/day. Mating was
unaffected in this study.
In a reproduction study of acetylcysteine, male rats were treated orally for 15 weeks prior to mating and during
the mating period. A slight non-dose related reduction in fertility was observed at oral doses of 500 and 1000
mg/kg/day (0.1 and 0.3 times the recommended human dose, respectively, based on body surface area).
16 HOW SUPPLIED/STORAGE AND HANDLING
CETYLEV effervescent tablets are supplied as white, round, flat tablets with a lemon mint smell packaged in 2-
count peelable foil blister packs in the following dosage strengths:
500 mg tablets debossed with “I” on one side; Each carton containing 2-count blister packs (24338-700-
02)
o NDC 24338-700-10: 10 pack carton containing 20 tablets
2.5 gram tablets debossed with “O” on one side; Each carton containing 2-count blister packs (24338-
725-02)
o NDC 24338-725-10: 10 pack carton containing 20 tablets
Store at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP
Controlled Room Temperature.] Protect from moisture. Store tablets in original blister package until use.
Dilutions of acetylcysteine should be used freshly prepared and utilized within two hours.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Hypersensitivity Reactions
Advise patients that hypersensitivity reactions, including generalized urticaria may occur and to report any signs
or symptoms to their healthcare provider immediately [see Warnings and Precautions (5.1)].
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda
12
Manufactured for:
Atlanta, GA 30328
Made in Switzerland by Alpex Pharma SA.
CET-PI-02
Rev. 04/2017
Reference ID: 4083362
This label may not be the latest approved by FDA.
For current labeling information, please visit https://www.fda.gov/drugsatfda