Acetylcysteine (0101)
[ a-se-teel-sis'-tay-een ]
| Ingredients: |
Acetylcysteine |
| Indications: |
Amyloidosis, primary; Anesthesia, adjunct; Atelectasis, secondary to mucus obstruction; Bronchiectasis; Bronchitis, chronic; Cystic fibrosis; Emphysema; Overdose, acetaminophen; Pneumonia; Poisoning, acetaminophen; Pulmonary disease, chronic; Tracheobronchitis; Tracheostomy, adjunct; Tuberculosis |
| Pregnancy Category: |
B |
| FDA Approved: |
1963- 09- 01 |
| Classes: |
Antidotes; Mucolytics; Orphan Drugs; WHO Formulary |
| HCFA Jcodes: |
J7608, J7610, J7615 |
| Brand Names: |
ACC
-
Mexico
;
Acerac
-
Korea
;
Acetadote
-
US
;
Acetain
-
Korea
;
Acypront
-
Hong-kong
;
Acys-5
-
US
;
Alveolex
-
Ireland
;
Bromuc
-
Brazil
;
Cetilan
-
Korea
;
Drenaflen
-
Ecuador
;
Ecomucyl
-
Switzerland
;
Eloamin
-
Czech-republic
;
Encore
-
Taiwan
;
Exomuc
-
France, Hong-kong
;
Fabrol
-
Austria, England, Finland, Greece, Ireland, Sweden
;
Flemex-AC
-
Thailand
;
Fluimicil
-
Germany, Hungary, Switzerland
;
Fluimucil
-
Brazil, China, Colombia, Ecuador, France, Hong-kong, Indonesia, Italy, Morocco, Netherlands, Peru, Singapore, Spain, Taiwan, Thailand
;
Fluimucil A
-
Malaysia
;
Flutafin
-
Taiwan
;
Hidonac
-
Philippines
;
Libramucil
-
Ecuador
;
M.C.T.
-
Korea
;
Menaxol
-
Costa-rica, Dominican-republic, El-salvador, Guatemala, Honduras, Nicaragua, Panama
;
Mucidin
-
Korea
;
Mucofillin
-
Japan
;
Mucolator
-
Malaysia
;
Mucolitico
-
Chile
;
Mucomiste
-
Portugal
;
Mucomyst
-
Australia, Austria, Belgium, Canada, Denmark, France, Netherlands
;
Mucomyst-10
-
US
;
Mucomyst-20
-
US
;
Mucoserin
-
Korea
;
Mucosof
-
China
;
Mucosten
-
Korea
;
Mucoza
-
Singapore, Thailand
;
Mukolit
-
Indonesia
;
Muteran
-
Korea
;
Parvolex
-
Canada, Philippines
;
Parvolex DBL
-
Malaysia
;
Reolin
-
Israel
;
Siran 200
-
Israel
;
Solmucol
-
Singapore
;
Spatam
-
Singapore
;
Stecin
-
Korea
;
Zifluvis
-
Colombia
;
|
| DEA schedules: |
(none)
|
| Cost of therapy: |
$195.60
(
Acetaminophen Overdose ;
Generic (Roxane) ;
20%; 30 ml ;
90 g total (approximate) ;
90 ml
)
$266.55
(
Acetaminophen Overdose ;
Mucomyst ;
20%; 30 ml ;
90 g total (approximate) ;
90 ml
)
$60.85
(
Pulmonary Disease (mucolytic) ;
Generic (Roxane) ;
20%; 30 ml ;
20 ml/day (nebulizer) ;
7 day supply
)
$82.93
(
Pulmonary Disease (mucolytic) ;
Mucomyst ;
20%; 30 ml ;
20 ml/day (nebulizer) ;
7 day supply
)
$36.52
(
Tracheostomy (mucolytic) ;
Generic (Roxane) ;
20%; 30 ml ;
12 ml daily inhalation ;
7 day supply
)
$49.76
(
Tracheostomy (mucolytic) ;
Mucomyst ;
20%; 30 ml ;
12 ml/day (intratracheal) ;
7 day supply
)
|
Administration Route:Inhalation
DESCRIPTION
|
| |
Acetylcysteine is for inhalation (mucolytic agent) or oral administration (acetaminophen antidote), and available as sterile,
unpreserved solutions (not for injection). The solutions contain 20% or 10% acetylcystine, with disodium edetate in purified
water. Sodium hydroxide is added to adjust pH to7. Acetylcystine is the N- acetyl derivative of the N- acetyl derivative of
the naturally occurring amino acid, cysteine. The compound is a white crystalline powder with the molecular formula C5 H9 NO3 S, a molecular weight of 163.2, and chemical name of N- acetyl- L- cysteine.
This product contains the following inactive ingredients: disodium edetate, sodium hydroxide, and purified water.
|
CLINICAL PHARMACOLOGY
|
| |
The viscosity of pulmonary mucous secretions depends on the concentrations of mucoprotein and to a lesser extent deoxyribonucleic
acid (DNA). The latter increases with increasing purulence owing to cellular debris. The mucolytic action of acetylcysteine
is related to the sulfhydryl group in the molecule. This group probably "opens" disulfide linkages in mucous thereby lowering
the viscosity. The mucolytic activity of acetylcysteine is unaltered by the presence of DNA, and increases with increasing
pH. Significant mucolysis occurs between pH 7 and 9.
Acetylcysteine undergoes rapid deacetylation in vivo to yield cysteine or oxidation to yield diacetylcystine.
Occasionally, patients exposed to the inhalation of an acetylcysteine aerosol respond with the development of increased airways
obstruction of varying and unpredictable severity. Those patients who are reactors cannot be identified a priori from a random patient population. Even when patients are known to have reacted previously to the inhalation of an acetylcysteine
aerosol, they may not react during a subsequent treatment. The converse is also true; patients who have had inhalation treatments
of acetylcysteine without incident may still react to a subsequent inhalation with increased airways obstruction. Most patients
with bronchospasm are quickly relieved by the use of a bronchodilator given by nebulization. If bronchospasm progresses, the
medication should be discontinued immediately.
As an Antidote for Acetaminophen Overdose
|
| |
(Antidotal) Acetaminophen is rapidly absorbed from the upper gastrointestinal tract with peak plasma levels occurring between
30 and 60 minutes after therapeutic doses and usually within 4 hours following an overdose. The parent compound, which is
nontoxic, is extensively metabolized in the liver to form principally the sulfate and glucuronide conjugates which are also
nontoxic and are rapidly excreted in the urine. A small fraction of an ingested dose is metabolized in the liver by the cytochrome
P- 450 mixed function oxidase enzyme system to form a reactive, potentially toxic, intermediate metabolite which preferentially
conjugates with hepatic glutathione to form the nontoxic cysteine and mercapturic acid derivatives which are then excreted
by the kidney. Therapeutic doses of acetaminophen do not saturate the glucuronide and sulfate conjugation pathways and do
not result in the formation of sufficient reactive metabolic to deplete glutathione stores. However, following ingestation
of a large overdose (150 mg/ kg or greater) the glucuronide and sulfate conjugation pathways are saturated resulting in a
larger fraction of the drug being metabolized via the P- 450 pathway. The increased formation of reactive metabolite may deplete
the hepatic stores of glutathione with subsequent binding of the metabolite to protein molecules within the hepatocyte resulting
in cellular necrosis. Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose.
Its effectiveness depends on early administration, with benefit seen principally in patients treated within 16 hours of the
overdose. Acetylcysteine probably 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.
|
|
INDICATIONS AND USAGE
|
| |
Acetylcysteine is indicated as 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).
Acetylcysteine as an Antidote for Acetaminophen Overdose
|
| |
Acetylcysteine, administered orally, is indicated as an antidote to prevent or lessen hepatic injury which may occur following
the ingestion of a potentially hepatotoxic quantity of acetaminophen.
It is essential to initiate treatment as soon as possible after the overdose and, in any case, within 24 hours of ingestion.
|
|
CONTRAINDICATIONS
|
| |
Acetylcysteine is contraindicated in those patients who are sensitive to it.
Acetylcysteine as an Antidote for Acetaminophen Overdose
|
| |
There are no contraindications to oral administration of acetylcysteine in the treatment of acetaminophen overdose.
|
|
WARNINGS
|
| |
After proper administration of acetylcysteine, an increased volume of liquefied bronchial secretions may occur. When cough
is inadequate, the open airway must be maintained by mechanical suction if necessary. When there is a large 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. If bronchospasm progresses, the medication should
be discontinued immediately.
As an Antidote for Acetaminophen Overdose
|
| |
Generalized urticaria has been observed rarely in patients receiving oral acetylcysteine for acetaminophen overdose. If this
occurs or other allergic symptoms appear, treatment with acetylcysteine should be discontinued unless it is deemed essential
and the allergic symptoms can be otherwise controlled.
If encephalopathy due to hepatic failure becomes evident, acetylcysteine treatment should be discontinued to avoid further
administration of nitrogenous substances. There are no data indicating that acetylcysteine adversely influences hepatic failure,
but this remains a theoretical possibility.
|
|
PRECAUTIONS
|
| |
With the administration of acetylcysteine, the patient may initially notice a slight disagreeable odor which soon is not noticeable.
With a face mask there may be a stickiness on the face after nebulization which is easily removed by washing with water.
Under certain conditions, a color change may take place in the solution of acetylcysteine in the opened bottle. The light
purple color is the result of a chemical reaction which does not significantly impair the safety or mucolytic effectiveness
of acetylcysteine.
Continued nebulization of an acetylcysteine solution with a dry gas will result in an increased concentration of the drug
in the nebulizer because of evaporation of the solvent. Extreme concentration may impede nebulization and efficient delivery
of the drug. Dilution of the nebulizing solutions with sterile water for injection as concentration occurs, will obviate this
problem.
As an Antidote for Acetaminophen Overdose
|
| |
Occasionally severe and persistent vomiting occurs as a symptom of acute acetaminophen overdose. Treatment with oral acetylcysteine
may aggravate the vomiting. Patients at risk of gastric hemorrhage ( e.g., esophageal varices, peptic ulcers, etc.) should be evaluated concerning the risk of upper gastrointestinal hemorrhage versus
the risk of developing hepatic toxicity, and treatment with acetylcysteine given accordingly.
Dilution of the acetylcysteine minimizes the propensity of oral acetylcysteine to aggravate vomiting.
|
Carcinogenesis, Mutagenesis, and Impairment of Fertility
|
| |
Carcinogenesis
|
| |
Carcinogenicity studies in laboratory animals have not been performed with acetylcysteine in combination with isoproterenol.
Long- term oral studies of acetylcysteine alone in rats (12 months of treatment followed by 6 months of observation) at doses
up to 1000 mg/ kg/ day (5.2 times the human dose) provided no evidence of oncogenic activity.
|
Mutagenesis
|
| |
Published data* indicate that acetylcysteine is not mutagenic in the Ames test, both with and without metabolic activation.
|
Impairment of Fertility
|
| |
A reproductive toxicity test to assess potential impairment of fertility was performed with acetylcysteine (10%) combined
with isoproterenol (0.05%) and administered as an aerosol into a chamber of 12.43 m3. The combination was administered for 25, 30, or 35 twice a day for 68 days before mating, to 200 male and 150 female rats;
no adverse effects were noted in dams or pups. Females after mating were continued on treatment for the next 42 days.
Reproductive toxicity studies of acetylcysteine in the rat given oral doses of acetylcysteine up to 1000 mg/ kg (2.6 or 5.2
times the human dose) in the Segment 1 Study.
|
|
Pregnancy Category B
|
| |
Reproduction studies of acetylcysteine with isoproterenol have been performed in rats and of acetylcysteine alone in rabbits
at doses up to 2.6 times the human dose. These have revealed no evidence of impaired fertility or harm to the fetus due to
acetylcysteine. There are, however, no adequate and well- controlled studies in pregnant women. Because animal reproduction
studies may not always be predictiveness of responses, this drug should be used during pregnancy only if clearly needed.
Teratogenic Effects
|
| |
In a teratology study of acetylcysteine in the rabbit, oral doses of 500 mg/ kg/ day (2.6 times the human dose) were administered
to pregnant does by intubation on days 6 through 16 of gestation. Acetylcysteine was found to be nonteratogenic under the
conditions of study.
In the rabbit, 2 groups (one of 14 and one of 16 pregnant females) were exposed to an aerosol of 10% acetylcysteine and 0.05%
isoproterenol HCl for 30 or 35 minutes twice a day from the 6ththrough the 18thday of pregnancy. No teratogenic effects were observed among the offspring.
Teratology and a perinatal and postnatal toxicity study in rats were performed with a combination of acetylcysteine and isoproterenol
administered by the inhalation route. In the rat, 2 groups of 25 pregnant females each were exposed to the aerosol for 30
and 35 minutes, respectively, twice a day from the 6ththrough the 15thday of gestation. No teratogenic effects were observed among the offspring.
In the pregnant rat (30 rats per group), twice- daily exposure to an aerosol of acetylcysteine and isoproterenol for 30 or
35 minutes from the 15thday of gestation through the 21thday postpartum was without adverse effect on dams or newborns.
|
|
Nursing Mothers
|
| |
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should
be exercised when acetylcysteine is administered to a pregnant woman.
|
|
ADVERSE REACTIONS
|
| |
Adverse effects have included stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and
bronchoconstriction. Clinically overt acetylasthmatics bronchospasm occurs infrequently and unpredictably even in patients
with asthmatic bronchitis or bronchitis complicating bronchial asthma. Acquired sensitization to acetylcysteine has been reported
rarely. Reports of sensitization in patients have not been confirmed by patch testing. Sensitization has been confirmed in
several inhalation therapists who reported a history of dermal eruptions after frequent and extended exposure to acetylcysteine.
Reports of irritation to the tracheal and bronchial tracts have been received and although hemoptysis has occurred in patients
receiving acetylcysteine such findings are not uncommon in patients with bronchopulmonary disease and a causal relationship
has not been established.
As an Antidote for Acetaminophen Overdose
|
| |
Oral administration of acetylcysteine, especially in the large doses needed to treat acetaminophen overdose, may result in
nausea, vomiting and other gastrointestinal symptoms. Rash with or without mild fever has been observed rarely.
|
|
DOSAGE AND ADMINISTRATION
|
| |
Acetylcysteine solution 10% and 20%, is available in glass vials containing 4 or 30 ml. The 20% solution may be diluted to
a lesser concentration with either sodium chloride inhalation solution, sodium chloride injection, or sterile water for injection.
The 10% solution may be used undiluted.
Acetylcysteine does not contain an antimicrobial agent, and care must be taken to minimize contamination of the sterile solution.
If only a portion of the solution in a vial is used, store the remainder in a refrigerator and use within 96 hours.
- Nebulization — Face Mask, Mouth Piece, Tracheostomy: When nebulized into a face mask, mouth piece or tracheostomy, 1- 10 ml of the 20% solution or 2- 20 ml of the 10% solution
may be given every 2- 6 hours; the recommended dose for most patients is 3- 5 ml of the 20% solution or 6- 10 ml of the 10%
solution 3- 4 times a day.
- Nebulization Tent, Croupette: In special circumstances it may be necessary to nebulize into a tent or Croupette, and this method of use must be individualized
to take into account the available equipment and the patient's particular needs. This form of administration requires very
large volumes of the solution, occasionally as much as 300 ml during a single treatment period. If a tent or Croupette must
be used, the recommended dose is the volume of solution (using 10% or 20% acetylcysteine) that will maintain a very heavy
mist in the tent or Croupette for the desired period. Administration for intermittent or continuous prolonged periods, including
overnight, may be desirable.
- Direct Installation: When used by direct instillation, 1- 2 ml of the 10% or 20% solution may then be given as often as every hour.
- When used for the routine nursing care of patients with tracheostomy, 1- 2 ml of the 10 to 20% solution may be given every
1- 4 hours by instillation into the tracheostomy.
- Acetylcysteine may be introduced directly into a particular segment of the bronchopulmonary tree by inserting (under local
anesthesia and direct vision) a small plastic catheter into the trachea. Two to 5 ml of the 20% solution may then be instilled
by means of a syringe connected to the catheter.
- Acetylcysteine may also be given through a percutaneous intratracheal catheter. One to 2 ml of the 20% or 2- 4 ml of the 10%
solution every 1- 4 hours may then be given by a syringe attached to the catheter.
- Diagnostic Bronchograms: For diagnostic bronchial studies, 2 or 3 administrations of 1- 2 ml of the 20% solution or 2- 4 ml of the 10% solution should
be given by nebulization or by instillation intratracheally, prior to the procedure.
Compatibility
|
| |
The physical and chemical compatibility of acetylcysteine solutions with other drugs commonly administered by nebulization,
direct instillation, or topical application, has been studied.
Acetylcysteine should not be mixed with all antibiotics. For example, the antibiotics tetracycline HCl, oxytetracycline HCl,
and erythromycin lactobionate were found to be incompatible when mixed in the same solution. These agents may be administered
from separate solutions if administration of these agents is desirable.
If it is deemed advisable to prepare an admixture, it should be administered as soon as possible after preparation. Do not
store unused mixtures.
|
As an Antidote for Acetaminophen Overdose
|
| |
Regardless of the quantity of acetaminophen reported to have been ingested, administer acetylcysteine immediately if 24 hours
or less have elapsed from the reported time of ingestion of an overdose of acetaminophen. Do not await results of assays for
acetaminophen level before initiating treatment with acetylcysteine. The following procedures are recommended:
- 1. The stomach should be emptied promptly by lavage or by inducing emesis with syrup of ipecac. Syrup of ipecac should be given
in a dose of 15 ml for children up to age 12, and 30 ml for adolescents and adults followed immediately by copious quantities
of water. The dose should be repeated if emesis does not occur in 20 minutes.
- 2. In the case of a mixed drug overdose activated charcoal may be indicated. However, if activated charcoal has been administered,
lavage before administering acetylcysteine treatment. Activated charcoal adsorbs acetylcysteine in vitro and may do so in patients and thereby may reduce in effectiveness.
- 3. Draw blood for acetaminophen plasma assay and for baseline SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood
sugar and electrolytes. The acetaminophen assay provides a basis for determining the need for continuing with the maintenance
doses of acetylcysteine treatment. If an assay cannot be obtained or if the acetaminophen level is clearly in the toxic range
(above the dashed line of the nomogram) dosing with acetylcysteine should be continued for the full course of therapy. The
laboratory measurements are used to monitor hepatic and renal function and electrolyte and fluid balance.
- 4. Administer the loading dose of acetylcysteine, 140 mg/ kg of body weight. (Prepare acetylcysteine for oral administration
as described in TABLE 1 .)
- 5. Four hours after the loading dose administer the first maintenance dose (70 mg of acetylcysteine per kg of body weight). The
maintenance dose is then repeated at 4- hour intervals for a total of 17 doses unless the acetaminophen assay reveals a nontoxic
level as discussed below.
- 6. If the patient vomits the loading dose or any maintenance dose within 1 hour of administration, repeat the dose.
- 7. In the occasional instances where the patient is persistently unable to retain the orally administered acetylcysteine, the
antidote may be administered by duodenal intubation.
- 8. Repeat SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar and electrolytes daily if the acetaminophen plasma
level is in the potentially toxic range as discussed below.
| TABLE 1
Dosage Guide and Preparation
|
| Doses in relation to body weight are: |
| Body Weight |
Acetylcysteine |
Diluent |
5% Solution |
| kg |
lb |
g |
ml of 20% |
ml |
Total ml |
| Loading Dose of Acetylcysteine**
|
| 100- 109 |
220- 240 |
15 |
75 |
225 |
300 |
| 90- 99 |
198- 218 |
14 |
70 |
210 |
280 |
| 80- 89 |
176- 196 |
13 |
65 |
195 |
260 |
| 70- 79 |
154- 174 |
11 |
55 |
165 |
220 |
| 60- 69 |
132- 152 |
10 |
50 |
150 |
200 |
| 50- 59 |
110- 130 |
8 |
40 |
120 |
160 |
| 40- 49 |
88- 108 |
7 |
35 |
105 |
140 |
| 30- 39 |
66- 86 |
6 |
30 |
90 |
120 |
| 20- 29 |
44- 64 |
4 |
20 |
60 |
80 |
| Maintenance Dose*
|
| 100- 109 |
220- 240 |
7.5 |
37 |
113 |
150 |
| 90- 99 |
198- 218 |
7 |
35 |
105 |
140 |
| 80- 89 |
176- 196 |
6.5 |
33 |
97 |
130 |
| 70- 79 |
154- 174 |
5.5 |
28 |
82 |
110 |
| 60- 69 |
132- 152 |
5 |
25 |
75 |
100 |
| 50- 59 |
110- 130 |
4 |
20 |
60 |
80 |
| 40- 49 |
88- 108 |
3.5 |
18 |
52 |
70 |
| 30- 39 |
66- 86 |
3 |
15 |
45 |
60 |
| 20- 29 |
44- 64 |
2 |
10 |
30 |
40 |
|
| *
|
If patient weighs less than 20 kg (usually patients younger than 6 years), calculate the doses of acetylcysteine solution.
Each ml of 20% acetylcysteine solution, contains 200 mg of acetylcysteine. The loading dose is 140 mg/ kg of body weight.
The maintenance dose is 70 mg/ kg. Three (3) ml of diluent are added to each ml of 20% acetylcysteine solution. Do not decrease
the proportion of diluent.
|
|
|
Supportive Treatment Of Acetaminophen Overdose
|
| |
- 1. Maintain fluid and electrolyte balance based on clinical evaluation of state of hydration and serum electrolytes.
- 2. Treat as necessary for hypoglycemia.
- 3. Administer vitamin K1 if prothrombin time ratio exceeds 1.5 or fresh frozen plasma if the prothrombin time ratio exceeds 3.0.
- 4. Diuretics and forced diuresis should be avoided (see TABLE 1 ).
|
|
Administration Route:Injection
DESCRIPTION
|
| |
Acetylcysteine injection is an IV medication for the treatment of acetaminophen overdose. Acetylcysteine is the nonproprietary
name for the N- acetyl derivative of the naturally occurring amino acid, L- cysteine (N- acetyl- L- cysteine, NAC). The compound
is a white crystalline powder, which melts in the range of 104- 110°C and has a very slight odor. The molecular formula of
the compound is C5 H9 NO3 S, and its molecular weight is 163.2.
Acetadote is supplied as a sterile solution in vials containing 20% w/ v (200 mg/ ml) acetylcysteine. The pH of the solution
ranges from 6.0- 7.5. Acetadote contains the following inactive ingredients: 0.5 mg/ ml disodium edetate, sodium hydroxide
(used for pH adjustment), and sterile water for injection.
|
CLINICAL PHARMACOLOGY
|
| |
Acetaminophen Overdose
|
| |
Acetaminophen is absorbed from the upper gastrointestinal tract with peak plasma levels occurring between 30 and 60 minutes
after therapeutic doses and usually within 4 hours following an overdose. It is extensively metabolized in the liver to form
principally the sulfate and glucuronide conjugates which are excreted in the urine. A small fraction of an ingested dose is
metabolized in the liver by isozyme CYP2E1 of the cytochrome P- 450 mixed function oxidase enzyme system to form a reactive,
potentially toxic, intermediate metabolite. The toxic metabolite preferentially conjugates with hepatic glutathione to form
nontoxic cysteine and mercapturic acid derivatives, which are then excreted by the kidney. Recommended therapeutic doses of
acetaminophen are not believed to saturate the glucuronide and sulfate conjugation pathways and therefore are not expected
to result in the formation of sufficient reactive metabolite to deplete glutathione stores. However, following ingestion of
a large overdose, the glucuronide and sulfate conjugation pathways are saturated resulting in a larger fraction of the drug
being metabolized via the cytochrome P- 450 pathway and therefore, the amount of acetaminophen metabolized to the reactive
intermediate increases. The increased formation of the reactive metabolite may deplete the hepatic stores of glutathione with
subsequent binding of the metabolite to protein molecules within the hepatocyte resulting in cellular necrosis.
|
Acetylcysteine IV Treatment
|
| |
Acetylcysteine has been shown to reduce the extent of liver injury following acetaminophen overdose. It is most effective
when given early, with benefit seen principally in patients treated within 8- 10 hours of the overdose. Acetylcysteine likely
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.
|
Pharmacokinetics
|
| |
Distribution
|
| |
The steady- state volume of distribution (Vdss ) and the protein binding for acetylcysteine were reported to be 0.47 L/ kg and 83%, respectively.
|
Metabolism
|
| |
Acetylcysteine may form cysteine, disulfides, and conjugates in vivo (N, N’- diacetylcysteine, N- acetylcysteine- cysteine, N- acetylcysteine- glutathione, N- acetylcysteine- protein, etc.).
Based on published data, it was reported that after an oral dose of35S- acetylcysteine, about 22% of total radioactivity was excreted in urine after 24 hours. No metabolites were identified.
|
Elimination
|
| |
After a single IV dose of acetylcysteine, the plasma concentration of total acetylcysteine declined in a polyexponential decay
manner with a mean terminal half- life (T1/ 2 ) of 5.6 hours. The mean clearance (CL) for acetylcysteine was reported to be 0.11 L/ h/ kg and renal CL constituted about
30% of total CL.
|
Special Populations
|
| |
Gender
|
| |
Adequate information is not available to assess if there are differences in pharmacokinetics (PK) between males and females.
|
Pediatric
|
| |
The mean elimination T1/ 2 of acetylcysteine is longer in newborns (11 hours) than in adults (5.6 hours). Pharmacokinetic information is not available
in other age groups.
|
Pregnant Women
|
| |
In 4 pregnant women with acetaminophen toxicity, oral or IV acetylcysteine was administered at the time of delivery. Acetylcysteine
was detected in the cord blood of 3 viable infants and in cardiac blood of a fourth infant, sampled at autopsy.
|
Hepatic Impairment
|
| |
In subjects with severe liver damage, i.e., cirrhosis due to alcohol (with Child- Pugh score of 7- 13), or primary and/ or secondary biliary cirrhosis (with Child- Pugh
score of 5- 7), mean T1/ 2 increased by 80% while mean CL decreased by 30% compared to control group.
|
Renal Disease
|
| |
Pharmacokinetic information is not available in patients with renal impairment.
|
Geriatric Patients
|
| |
Adequate information on acetylcysteine PK in geriatric patients is not available.
|
Drug-Drug Interactions
|
| |
No drug- drug interaction studies have been conducted.
|
|
|
|
CLINICAL STUDIES
|
| |
Safety Study
|
| |
A randomized, open- label, multicenter clinical study was conducted in Australia to compare the rates of anaphylactoid reactions
between two rates of infusion for the IV acetylcysteine loading dose. One hundred nine (109) subjects were randomized to a
15- minute infusion rate and 71 subjects were randomized to a 60- minute infusion rate. The loading dose was 150 mg/ kg followed
by a maintenance dose of 50 mg/ kg over 4 hours and then 100 mg/ kg over 16 hours. Of the 180 patients, 27% were male and
73% were female. Ages ranged from 15- 83 years, with the mean age being 29.9 years (+13.0).
Within the first 2 hours following IV acetylcysteine administration, 17% developed an anaphylactoid reaction (18% in the 15-
minute treatment group; 14% in the 60- minute treatment group). (See WARNINGS .) A subgroup of 58 subjects (33 in the 15- minute treatment group; 25 in the 60- minute group) was treated within 8 hours
of acetaminophen ingestion. No hepatotoxicity occurred within this subgroup; however with 95% confidence, the true hepatotoxicity
rates could range from 0- 9% for the 15- minute treatment group and from 0- 12% for the 60- minute treatment group.
|
Observational Study
|
| |
An open- label, observational database contained information on 1749 patients who sought treatment for acetaminophen overdose
over a 16- year period. Of the 1749 patients, 65% were female, 34% were male, and <1% was transgender. Ages ranged from 2
months to 96 years, with 71.4% of the patients falling in the 16- 40 year old age bracket. A total of 399 patients received
acetylcysteine treatment. A post- hoc analysis identified 56 patients who (1) were at high or probable risk for hepatotoxicity
(APAP >150 mg/ L at the 4 hours line according to the Australian nomogram) and (2) had a liver function test. Of the 53 patients
who were treated with IV acetylcysteine (300 mg/ kg IV acetylcysteine administered over 20- 21 hours) within 8 hours, 2 (4%)
developed hepatotoxicity (AST or ALT >1000 U/ L). Twenty- one (21) of 48 (44%) patients treated with acetylcysteine after
15 hours developed hepatoxicity. The actual number of hepatotoxicity outcomes may be higher than what is reported here. For
patients with multiple admissions for acetaminophen overdose, only the first overdose treated with IV acetylcysteine was examined.
Hepatotoxicity may have occurred in subsequent admissions.
|
|
CONTRAINDICATIONS
|
| |
Acetylcysteine is contraindicated in patients with hypersensitivity or previous anaphylactoid reactions to acetylcysteine
or any components in the preparation.
|
WARNINGS
|
| |
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- 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 IV acetylcysteine
for acetaminophen overdose and occurred soon after initiation of the infusion (see ADVERSE REACTIONS ). 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 as well as epinephrine in severe cases. 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,
IV acetylcysteine should be discontinued and alternative patient management should be considered. For additional information,
contact the American Association of Poison Control Centers (1- 800- 222- 1222).
|
PRECAUTIONS
|
| |
Acetylcysteine should be used with caution in patients with asthma, or where there is a history of bronchospasm. 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 as needed (see DOSAGE AND ADMINISTRATION ). If volume is not adjusted fluid overload can occur, potentially resulting in hyponatremia, seizure, and death.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
|
| |
Long- term studies in animals have not been performed to evaluate the carcinogenic potential of acetylcysteine.
Acetylcysteine was not genotoxic in the Ames test or the in vivo mouse micronucleus test. It was, however, positive in the in vitro mouse lymphoma cell (L5178Y/ TK+/ - ) forward mutation test.
Treatment of male rats with acetylcysteine at an oral dose of 250 mg/ kg/ day for 15 weeks (compared to the recommended total
human IV dose of 300 mg/ kg) did not affect the fertility or general reproductive performance.
|
Pregnancy, Teratogenic Effects, Pregnancy Category B
|
| |
Teratology studies were performed in rats at oral doses up to 2000 mg/ kg/ day and in rabbits at oral doses up to 1000 mg/
kg/ day (compared to the recommended total human IV dose of 300 mg/ kg) and revealed no evidence of impaired fertility or
harm to the fetus due to acetylcysteine. There are, however, no adequate and well- controlled studies in pregnant women. Because
animal reproduction studies may not always be predictive of human response, this drug should be used during pregnancy only
if clearly needed.
|
Pregnant Women
|
| |
In 4 pregnant women with acetaminophen toxicity, oral or IV acetylcysteine was administered at the time of delivery. Acetylcysteine
crossed the placenta and was measurable in newborn circulation and cord blood of 3 viable infants following delivery and in
cardiac blood of a fourth infant at autopsy (22 weeks gestational age who died 3 hours after birth). No adverse sequelae developed
in the 3 viable infants. All mothers recovered and none of the infants had evidence of acetaminophen poisoning.
|
Nursing Mothers
|
| |
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should
be exercised when acetylcysteine is administered to a nursing woman.
|
Pediatric Patients
|
| |
No adverse effects were noted during IV infusion with acetylcysteine at a mean rate of 8.4 mg/ kg/ h for 24 hours to 10 preterm
newborns ranging in gestational age from 25- 31 weeks and in weight from 500- 1380 g in one study (Study 1) or in 6 newborns
ranging in gestational age from 26- 30 weeks and in weight from 520- 1335 g infused with acetylcysteine at 0.1- 1.3 mg/ kg/
h for 6 days (Study 2). Elimination of acetylcysteine was slower in these infants than in adults; mean elimination half- life
was 11 hours (Study 1).
|
Geriatric Patients
|
| |
The clinical studies do not provide a sufficient number of geriatric subjects to determine whether the elderly respond differently.
|
|
DRUG INTERACTIONS
|
| |
Drug stability and safety of acetylcysteine when mixed with other drugs have not been established.
|
ADVERSE REACTIONS
|
| |
In the literature the most frequently reported adverse events attributed to IV acetylcysteine administration were rash, urticaria,
and pruritus. The frequency of adverse events has been reported to be between 0.2 and 20.8%, and they most commonly occur
during the initial loading dose of acetylcysteine.
The incidence of drug- related adverse events occurring within the first 2 hours following acetylcysteine administration reported
in a randomized study (Infusion Rate Study) in patients with acetaminophen poisoning is presented in TABLE 2A and TABLE 2B by preferred term. In this study patients were randomized to a 15- minute or a 60- minute loading dose regimen.
| TABLE 2A
Incidence of Drug- Related Adverse Events Occurring Within the First 2 Hours Following Study Drug Administration by Preferred
Term: CMAX Study — 15- Minute Treatment Group (n=109)
|
| |
Severity |
| |
|
Unknown |
Mild |
Moderate |
Severe |
| Cardiac Disorders |
5 (5%) |
| |
Tachycardia NOS |
|
4 (4%) |
1 (1%) |
|
| Ear and Labyrinth Disorders |
1 (1%) |
| |
Ear pain |
|
|
1 (1%) |
|
| Gastrointestinal Disorders |
16 (15%) |
| |
Nausea |
1 (1%) |
|
6 (6%) |
|
| |
Vomiting NOS |
|
2 (2%) |
11 (10%) |
|
| General Disorders and Administration Site Conditions |
1 (1%) |
| |
Chest tightness |
|
1 (1%) |
|
|
| Immune System Disorders |
20 (18%) |
| |
Anaphylactoid reacton |
2 (2%) |
6(6%) |
11 (10%) |
1 (1%) |
| Respiratory, Thoracic and Mediastinal Disorders |
2 (2%) |
| |
Pharyngitis |
|
|
1 (1%) |
|
| |
Rhinorrhoea |
|
1 (1%) |
|
|
| Skin and SC Tissue Disorders |
6 (6%) |
| |
Pruritus |
|
1 (1%) |
|
|
| |
Rash NOS |
|
3 (3%) |
2 (2%) |
|
| Vascular Disorders |
2 (2%) |
| |
Flushing |
|
1 (1%) |
1 (1%) |
|
|
| TABLE 2B
Incidence of Drug- Related Adverse Events Occurring Within the First 2 Hours Fellowing Study Drug Administration by Preferred
Term: CMAX Study — 60- Minute Treatment Group (n=71)
|
| |
Severity |
| |
|
Unknown |
Mild |
Moderate |
Severe |
| Cardiac Disorders |
2 (3%) |
| |
Tachycardia NOS |
|
2 (3%) |
|
|
| Ear and Labyrinth Disorders |
0 (0%) |
| |
Ear pain |
|
|
|
|
| Gastrointestinal Disorders |
7 (105%) |
| |
Nausea |
|
1 (1%) |
1 (1%) |
|
| |
Vomiting NOS |
|
2 (3%) |
4 (6%) |
|
| General Disorders and Administration Site Conditions |
1 (1%) |
| |
Chest Tightness |
|
|
|
|
| |
Feeling Hot |
|
1 (1%) |
|
|
| Immune System Disorders |
10 (14%) |
| |
Anaphylactoid r eacton |
|
4 (6%) |
5 (7%) |
1 (1%) |
| Respiratory, Thoracic and Mediastinal Disorders |
2 (3%) |
| |
Rhonchi |
|
1 (1%) |
|
|
| |
Throat tightness |
|
1 (1%) |
|
|
| Skin and SC Tissue Disorders |
5 (7%) |
| |
Pruritus |
|
2 (3%) |
|
|
| |
Rash NOS |
|
3 (4%) |
|
|
| Vascular Disorders |
3 (4%) |
| |
Flushing |
|
2 (3%) |
1 (1%) |
|
|
Adverse events summarized by the Rocky Mountain Poison and Drug Center from 76 published articles in which IV acetylcysteine
was administered (acetaminophen overdose and other published uses) are listed with an incidence greater than 1% in TABLE 3 . Charcoal, naloxone, and benzodiazepines were administered concomitantly in several of these studies.
| TABLE 3
Adverse Events Greater Than 1% by Body System: Published Clinical Studies, Acetaminophen Overdose and Other Published Uses
|
| |
|
|
Frequency in Patients With Safety Monitoring |
| Body System Classification |
Adverse Event Occurences |
Distribution of All Adverse Events |
n=2040 |
| Body as a Whole & Combinations
|
| |
Urticaria |
34 |
7.96% |
1.67% |
| |
Vasodilatation and rash |
30 |
7.03% |
1.47% |
| |
Vasodilatation, rash, and pruritus |
42 |
9.84% |
2.06% |
| Cardiovascular System
|
| |
Hypotension |
16 |
3.75% |
0.78% |
| |
Syncope |
13 |
3.04% |
0.64% |
| |
Vasodilatation |
28 |
6.56% |
1.37% |
| Digestive System
|
| |
Dyspepsia |
5 |
1.17% |
0.24% |
| |
Nausea |
43 |
10.07% |
2.11% |
| |
Vomiting |
15 |
3.51% |
0.24% |
| Nervous System
|
| |
Abnormal thinking (dysphoria) |
8 |
1.87% |
0.39% |
| |
Gait disturbances |
5 |
1.17% |
0.24% |
| Respiratory System
|
| |
Bronchospasm |
25 |
5.85% |
1.23% |
| |
Coughing |
18 |
4.22% |
0.88% |
| |
Dyspnea |
11 |
2.58% |
0.54% |
| Skin & Appendages
|
| |
Angioedema |
33 |
7.73% |
1.62% |
| |
Facial erythema |
5 |
1.17% |
0.24% |
| |
Palmar erythema |
6 |
1.41% |
0.29% |
| |
Pruritus |
5 |
1.17% |
0.24% |
| |
Pruritus and rash |
7 |
1.64% |
0.34% |
| |
Rash |
21 |
4.92% |
1.03% |
| |
Sweating |
6 |
1.41% |
0.29% |
| Special Senses
|
| |
Pain – eye |
11 |
2.58% |
0.54% |
|
|
OVERDOSAGE
|
| |
Single IV doses of acetylcysteine at 1000 mg/ kg in mice, 2445 mg/ kg in rats, 1500 mg/ kg in guinea pigs, 1200 mg/ kg in
rabbits and 500 mg/ kg in dogs were lethal. Symptoms of acute toxicity were ataxia, hypoactivity, labored respiration, cyanosis,
loss of righting reflex and convulsions.
|
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 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 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 µg/ ml at 4 hours with 37.5 µg/ 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 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 is between 0- 8 hours. Efficacy
diminishes progressively after 8 hours and treatment initiation between 15- 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 IV 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 IV administration.
Stability
- Stability studies indicate that the reconstituted solution is stable for 24 hours at controlled room temperature.
- Acetylcysteine is not compatible with rubber and metals, particularly iron, copper and nickel.
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 3- fold 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 Acetylcysteine for IV 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 IV administration.
Dosage Guide and Preparation
|
| |
| TABLE 4
Dosage Guide in Relation to Body Weight: Adult Patients
|
| |
Acetylcysteine |
| |
FIRST |
SECOND |
THIRD |
| Body Weight |
150 mg/ kg in 200 ml 5% Dextrose in 15 min |
50 mg/ kg in 500 ml 5% Dextrose in 4 hours |
100 mg/ kg in 1000 ml 5% Dextrose in 16 hours |
| 100 kg (220 lb) |
75 ml |
25 ml |
50 ml |
| 90 kg (198 lb) |
67.5 ml |
22.5 ml |
45 ml |
| 80 kg (176 lb) |
60 ml |
20 ml |
40 ml |
| 70 kg (154 lb) |
52.5 ml |
17.5 ml |
35 ml |
| 60 kg (132 lb) |
45 ml |
15 ml |
30 ml |
| 50 kg (110 lb) |
37.5 ml |
12.5 ml |
25 ml |
| 40 kg (88 lb) |
30 ml |
10 ml |
20 ml |
|
|
|
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 4 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
- 1. When results of the plasma acetaminophen assay are available, refer to the nomogram below to determine if plasma concentration
is in the potentially toxic range. Values above the line connecting 200 µg/ ml at 4 hours with 50 µg/ 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 µg/ ml at 4 hours with 37.5 µg/ 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 µg/ ml at 4 hours with 37.5 µg/ ml at 12 hours (possible
line), there is minimal risk of hepatic toxicity, and acetylcysteine treatment may be discontinued.
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 (noninclusive)
- 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 IV administration. It is available as follows: 30 ml vials.
Storage: Store unopened vials at controlled room temperature, 20- 25°C (68- 77°F).
|
PRODUCT IDENTIFICATION
|
| |
None Available |
PRODUCT LISTING - RATED THERAPEUTICALLY EQUIVALENT
|
| |
| solution - inhalation - 10% -
|
| 4.0 ml x 10.0 |
$16.88 |
GENERIC
Mayne Pharma Inc
|
61703020304 |
| 4.0 ml x 12.0 |
$30.74 |
GENERIC
Roxane Laboratories Inc
|
00054805905 |
| 4.0 ml x 12.0 |
$59.88 |
GENERIC
Dey Laboratories
|
49502018104 |
| 4.0 ml x 12.0 |
$62.04 |
Mucomyst- 10
Bristol- Myers Squibb
|
00087057203 |
| 4.0 ml x 12.0 |
$63.72 |
GENERIC
American Regent Laboratories Inc
|
00517750412 |
| 4.0 ml x 25.0 |
$132.75 |
GENERIC
American Regent Laboratories Inc
|
00517750425 |
| 10.0 ml x 3.0 |
$10.89 |
GENERIC
Bedford Laboratories
|
55390021103 |
| 10.0 ml x 3.0 |
$19.56 |
GENERIC
Roxane Laboratories Inc
|
00054302702 |
| 10.0 ml x 3.0 |
$31.26 |
Mucomyst- 10
Bristol- Myers Squibb
|
00087057201 |
| 10.0 ml x 3.0 |
$39.39 |
GENERIC
American Regent Laboratories Inc
|
00517751003 |
| 10.0 ml x 3.0 |
$40.26 |
GENERIC
Dey Laboratories
|
49502018110 |
| 30.0 ml x 3.0 |
$27.36 |
GENERIC
Abbott Pharmaceutical
|
00074330703 |
| 30.0 ml x 3.0 |
$30.17 |
GENERIC
Bedford Laboratories
|
55390021203 |
| 30.0 ml x 3.0 |
$34.95 |
GENERIC
Roxane Laboratories Inc
|
00054302502 |
| 30.0 ml x 3.0 |
$39.75 |
GENERIC
Dey Laboratories
|
49502018130 |
| 30.0 ml x 3.0 |
$52.26 |
Mucomyst- 10
Bristol- Myers Squibb
|
00087057202 |
| 30.0 ml x 3.0 |
$105.00 |
GENERIC
American Regent Laboratories Inc
|
00517753003 |
| 30.0 ml x 10.0 |
$184.26 |
GENERIC
Mayne Pharma Inc
|
61703020331 |
| solution - inhalation - 20% -
|
| 4.0 ml x 10.0 |
$22.56 |
GENERIC
Abbott Pharmaceutical
|
00074330801 |
| 4.0 ml x 12.0 |
$33.54 |
GENERIC
Roxane Laboratories Inc
|
00054806005 |
| 4.0 ml x 10.0 |
$62.00 |
GENERIC
Mayne Pharma Inc
|
61703020404 |
| 4.0 ml x 12.0 |
$63.84 |
Mucomyst- 20
Bristol- Myers Squibb
|
00087057007 |
| 4.0 ml x 12.0 |
$66.00 |
GENERIC
Dey Laboratories
|
49502018204 |
| 4.0 ml x 25.0 |
$164.00 |
GENERIC
American Regent Laboratories Inc
|
00517760425 |
| 10.0 ml x 3.0 |
$9.00 |
GENERIC
Bedford Laboratories
|
55390021303 |
| 10.0 ml x 3.0 |
$24.45 |
GENERIC
Roxane Laboratories Inc
|
00054302802 |
| 10.0 ml x 3.0 |
$31.68 |
Mucomyst- 20
Bristol- Myers Squibb
|
00087057003 |
| 10.0 ml x 3.0 |
$45.93 |
GENERIC
American Regent Laboratories Inc
|
00517761003 |
| 10.0 ml x 3.0 |
$48.66 |
GENERIC
Dey Laboratories
|
49502018210 |
| 30.0 ml x 3.0 |
$23.44 |
GENERIC
Abbott Pharmaceutical
|
00074330803 |
| 30.0 ml x 3.0 |
$23.63 |
GENERIC
Bedford Laboratories
|
55390021403 |
| 30.0 ml x 3.0 |
$39.12 |
GENERIC
Roxane Laboratories Inc
|
00054302602 |
| 30.0 ml x 3.0 |
$43.50 |
GENERIC
Dey Laboratories
|
49502018230 |
| 30.0 ml x 3.0 |
$53.31 |
Mucomyst- 20
Bristol- Myers Squibb
|
00087057009 |
| 30.0 ml x 10.0 |
$113.75 |
GENERIC
Mayne Pharma Inc
|
61703020431 |
| 30.0 ml x 3.0 |
$128.43 |
GENERIC
American Regent Laboratories Inc
|
00517763003 |
| 100.0 ml |
$92.21 |
GENERIC
Dey Laboratories
|
49502018200 |
|
PRODUCT LISTING - EQUIVALENTS NOT AVAILABLE
|
| |
| powder - compounding - 100% -
|
| 25.0 gm |
$17.00 |
GENERIC
Medisca Inc
|
38779049525 |
| 25.0 gm |
$20.70 |
GENERIC
Spectrum Chemical
|
49452009701 |
| 100.0 gm |
$47.50 |
GENERIC
Medisca Inc
|
38779049510 |
| 100.0 gm |
$50.00 |
GENERIC
Spectrum Chemical
|
49452009702 |
| 500.0 gm |
$164.35 |
GENERIC
Medisca Inc
|
38779049550 |
| 500.0 gm |
$195.80 |
GENERIC
Spectrum Chemical
|
49452009704 |
| 1000.0 gm |
$348.00 |
GENERIC
Spectrum Chemical
|
49452009703 |
| solution - intravenous - 20% -
|
| 30.0 ml x 4.0 |
$541.25 |
Acetadote
Cumberland Pharmaceuticals Inc
|
66220010730 |
| 30.0 ml x 40.0 |
$5200.00 |
Acetadote
Cumberland Pharmaceuticals Inc
|
66220010734 |
| tablet - oral - 500 mg -
|
| 100.0's |
$20.38 |
Acys- 5
Bio- Tech Pharmacal Inc
|
53191019401 |
|
|