DOSAGE AND ADMINISTRATION
MUCOMYST is available in rubber stoppered glass vials containing 4, 10, or 30 mL. The 20% solution may be diluted to a lesser concentration with either Sodium Chloride for Injection, Sodium Chloride for Inhalation, Sterile Water for Injection, or Sterile Water for Inhalation. The 10% solution may be used undiluted.
MUCOMYST 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 for inhalation only within 96 hours.
NEBULIZATION—FACE MASK, MOUTH PIECE, TRACHEOSTOMY
When nebulized into a face mask, mouth piece, or tracheostomy, 1 to 10 mL of the 20% solution or 2 to 20 mL of the 10% solution may be given every 2 to 6 hours; the recommended dose for most patients is 3 to 5 mL of the 20% solution or 6 to 10 mL of the 10% solution 3 to 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 MUCOMYST (using 10% or 20%) 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.
When used by direct instillation, 1 to 2 mL of a 10% to 20% solution may be given as often as every hour.
When used for the routine nursing care of patients with tracheostomy, 1 to 2 mL of a 10% to 20% solution may be given every 1 to 4 hours by instillation into the tracheostomy.
MUCOMYST 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.
MUCOMYST may also be given through a percutaneous intratracheal catheter. One to 2 mL of the 20% or 2 to 4 mL of the 10% solution every 1 to 4 hours may then be given by a syringe attached to the catheter.
For diagnostic bronchial studies, two to three administrations of 1 to 2 mL of the 20% solution or 2 to 4 mL of the 10% solution should be given by nebulization or by instillation intratracheally, prior to the procedure.
Administration of Aerosol
MUCOMYST may be administered using conventional nebulizers made of plastic or glass. Certain materials used in nebulization equipment react with acetylcysteine. The most reactive of these are certain metals (notably iron and copper) and rubber. Where materials may come into contact with MUCOMYST solution, parts made of the following acceptable materials should be used: glass, plastic, aluminum, anodized aluminum, chromed metal, tantalum, sterling silver, or stainless steel. Silver may become tarnished after exposure, but this is not harmful to the drug action or to the patient.
Compressed tank gas (air) or an air compressor should be used to provide pressure for nebulizing the solution. Oxygen may also be used but should be used with the usual precautions in patients with severe respiratory disease and CO2 retention.
MUCOMYST is usually administered as fine nebulae and the nebulizer used should be capable of providing optimal quantities of a suitable range of particle sizes.
Commercially available nebulizers will produce nebulae of MUCOMYST satisfactory for retention in the respiratory tract. Most of the nebulizers tested will supply a high proportion of the drug solution as particles of less than 10 microns in diameter. Mitchell2 has shown that particles less than 10 microns should be retained in the respiratory tract satisfactorily.
Various intermittent positive pressure breathing devices nebulized MUCOMYST with a satisfactory efficiency including: No. 40 De Vilbiss (The De Vilbiss Co., Somerset, Pennsylvania) and the Bennett Twin-Jet Nebulizer (Puritan Bennett Corp., Oak at 13th, Kansas City, Missouri).
The nebulized solution may be inhaled directly from the nebulizer. Nebulizers may also be attached to plastic face masks or plastic mouthpieces. Suitable nebulizers may also be fitted for use with the various intermittent positive pressure breathing (IPPB) machines. The nebulizing equipment should be cleaned immediately after use because the residues may clog the smaller orifices or corrode metal parts.
Hand bulbs are not recommended for routine use for nebulizing MUCOMYST because their output is generally too small. Also, some hand-operated nebulizers deliver particles that are larger than optimum for inhalation therapy.
MUCOMYST should not be placed directly into the chamber of a heated (hot pot) nebulizer. A heated nebulizer may be part of the nebulization assembly to provide a warm saturated atmosphere if the MUCOMYST aerosol is introduced by means of a separate unheated nebulizer. Usual precautions for administration of warm saturated nebulae should be observed.
The nebulized solution may be breathed directly from the nebulizer. Nebulizers may also be attached to plastic face masks, plastic face tents, plastic mouth pieces, conventional plastic oxygen tents, or head tents. Suitable nebulizers may also be fitted for use with the various intermittent positive pressure breathing (IPPB) machines.
The nebulizing equipment should be cleaned immediately after use, otherwise the residues may occlude the fine orifices or corrode metal parts.
When three fourths of the initial volume of MUCOMYST solution have been nebulized, a quantity of Sterile Water for Injection (approximately equal to the volume of solution remaining) should be added to the nebulizer. This obviates any concentration of the agent in the residual solvent remaining after prolonged nebulization.
The physical and chemical compatibility of MUCOMYST solutions with certain other drugs that might be concomitantly administered by nebulization, direct instillation, or topical application has been studied.
MUCOMYST should not be mixed with certain antibiotics. For example, the antibiotics tetracycline hydrochloride, oxytetracycline hydrochloride, 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.
The supplying of these data should not be interpreted as a recommendation for combining MUCOMYST with other drugs. The table is not presented as positive assurance that no incompatibility will be present, since these data are based only on short-term compatibility studies done in the Mead Johnson Research Center. Manufacturers may change their formulations, and this could alter compatibilities. These data are intended to serve only as a guide for predicting compounding problems.
If it is deemed advisable to prepare an admixture, it should be administered as soon as possible after preparation. Do not store unused mixtures.
| IN VITRO COMPATIBILITY1 TESTS OF ACETYLCYSTEINE|
|PRODUCT AND/OR AGENT|| COMPATIBILITY|
|1. The rating, Incompatible, is based on the formation of a precipitate, a change in clarity, immiscibility, or a rapid loss of potency of acetylcysteine or the active ingredient of the PRODUCT AND/OR AGENT in the admixture.|
The rating, Compatible, means that there was no significant physical change in the admixture when compared with a control solution of the PRODUCT AND/OR AGENT, and that there was no predicted chemical incompatibility. All of the admixtures have been tested for short-term chemical compatibility by assaying for the concentration of acetylcysteine after mixing.
|2. The active ingredient in the PRODUCT AND/OR AGENT was also assayed after mixing. Some of the admixtures developed minor physical changes which were considered to be insufficient to rate the admixture Incompatible. These are listed in footnotes 3, 4, and 5.|
|3. A strong odor developed after storage for 24 hours at room temperature.|
|4. The admixture was a slightly darker shade of yellow than a control solution of the PRODUCT AND/OR AGENT.|
|5. A light tan color developed after storage for 24 hours at room temperature.|
|6. Entries are final concentrations. Values in parentheses relate volumes of MUCOMYST solutions to volume of test solutions. |
| ANESTHETIC, GAS |
| ANESTHETIC, LOCAL |
| ANTIBACTERIALS (A parenteral form of each antibiotic was used)|
|Bacitracin2,3 (mix and use at once) ||Compatible||10%||5,000 U/mL|
|Chloramphenicol Sodium Succinate||Compatible||20%||20 mg/mL|
(mix and use at once)
|Gentamicin Sulfate2||Compatible||10%||20 mg/mL|
(mix and use at once)
|Compatible ||10% ||167 mg/mL|
| Compatible ||17%||85 mg/mL|
|Lincomycin HCl2||Compatible||10%||150 mg/mL|
|Neomycin Sulfate2||Compatible||10%||100 mg/mL|
|Novobiocin Sodium2||Compatible||10%||25 mg/mL|
|Penicillin G Potassium2||Compatible||10%||25,000 U/mL|
|(mix and use at once)||Compatible||10%||100,000 U/mL|
|Polymyxin B Sulfate2||Compatible||10%||50,000 U/mL|
|Cephalothin Sodium||Compatible||10%||110 mg/mL|
| (mix and use at once)||Compatible||10%||37.5 mg/mL|
|Vancomycin HCl2||Compatible||10%||25 mg/mL|
|Amphotericin B||Incompatible||4%-15% ||1.0-4.0 mg/mL|
|Chlortetracycline HCl2||Incompatible||10%||12.5 mg/mL|
|Erythromycin Lactobionate ||Incompatible||10%||15 mg/mL|
|Oxytetracycline HCl||Incompatible||10%||12.5 mg/mL|
|Ampicillin Sodium ||Incompatible||10%||50 mg/mL|
|Tetracycline HCl||Incompatible||10%||12.5 mg/mL |
| BRONCHODILATORS |
|Isoproterenol HCl2||Compatible ||3.0% ||0.5%|
|Isoproterenol HCl2||Compatible ||10% ||0.05%|
|Isoproterenol HCl2|| Compatible||20%||0.05%|
|Isoproterenol HCl|| Compatible || 13.3% (2 parts)||.33% (1 part)|
|Isoetharine HCl|| Compatible ||13.3%||.33% (1 part)|
|Epinephrine HCl || Compatible ||13.3% (2 parts) ||.33% (1 part)|
| CONTRAST MEDIA |
|Iodized Oil||Incompatible ||20%/20 mL||40%/10 mL|
| DECONGESTANTS |
|Phenylephrine HCl2||Compatible||3.0% ||.25%|
|Phenylephrine HCl|| Compatible ||13.3% (2 parts)||.17% (1 part)|
| ENZYMES |
|Trypsin ||Incompatible||5%||400 γ/mL|
| SOLVENTS |
|Alcohol ||Compatible ||12%||10% - 20%|
|Propylene Glycol || Compatible || 3% ||10% |
| STEROIDS |
|Dexamethasone Sodium Phosphate ||Compatible||16%||0.8 mg/mL|
|Prednisolone Sodium Phosphate5||Compatible|| 16.7% ||3.3 mg/mL|
| OTHER AGENTS |
|Hydrogen Peroxide ||Incompatible||(All ratios)|
|Sodium Bicarbonate||Compatible ||20% (1 part) ||4.2% (1 part) |
MUCOMYST® (acetylcysteine solution, USP) As An Antidote for Acetaminophen Overdose
DOSAGE AND ADMINISTRATION
Regardless of the quantity of acetaminophen reported to have been ingested, administer MUCOMYST (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 MUCOMYST. The following procedures are recommended:
If the patient vomits any oral dose within 1 hour of administration, repeat that dose.
- 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 drinking copious quantities of water. The dose should be repeated if emesis does not occur in 20 minutes.
- 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 its effectiveness.
- Draw blood for predetoxification acetaminophen plasma assay and baseline SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar and electrolytes.
- Administer the loading dose of acetylcysteine, 140 mg per kg of body weight. (Prepare MUCOMYST for oral administration as described in the specific Dosage Guide and Preparation table.)
- Determine subsequent action based on predetoxification plasma acetaminophen information. Choose ONE of the following four courses of therapy.
Predetoxification plasma acetaminophen level is clearly in the toxic range (See Acetaminophen Assays - Interpretation and Methodology below):
Administer a first maintenance dose (70 mg/kg acetylcysteine) 4 hours after the loading dose. The maintenance dose is then repeated at 4-hour intervals for a total of 17 doses.
Monitor hepatic and renal function and electrolytes throughout the detoxification process.
Predetoxification acetaminophen level could not be obtained:
Proceed as in A.
Predetoxification acetaminophen level is clearly in the nontoxic range (beneath the dashed line on the nomogram) and you know that acetaminophen overdose occurred at least 4 hours before the predetoxification acetaminophen plasma assays:
Discontinue administration of acetylcysteine.
Predetoxification acetaminophen level was in the non-toxic range, but time of ingestion was unknown or less than 4 hours.
Because the level of acetaminophen at the time of the predetoxification assay may not be a peak value (peak may not be achieved before 4 hours post-ingestion), obtain a second plasma level in order to decide whether or not the full 17-dose detoxification treatment is necessary.
In the occasional instances where the patient is persistently unable to retain the orally administered acetylcysteine, the antidote may be administered by duodenal intubation.
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.
Preparation of Mucomyst (Acetylcysteine) for Oral Administration
Oral administration requires dilution of the 20% solution with diet cola or other diet soft drinks, to a final concentration of 5% (see Dosage Guide and Preparation table). If administered via gastric tube or Miller-Abbott tube, water may be used as the diluent. The dilutions should be freshly prepared and utilized within one hour. Remaining undiluted solutions in opened vials can be stored in the refrigerator up to 96 hours. MUCOMYST IS NOT APPROVED FOR PARENTERAL INJECTION.
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
- 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 solid line connecting 200 µg/mL at 4 hours with 50 µg/mL at 12 hours are associated with a possibility of hepatic toxicity if an antidote is not administered. (Do not wait for assay results to begin acetylcysteine treatment.)
- If the predetoxification plasma level is above the broken line continue with maintenance doses of acetylcysteine. It is better to err on the safe side and thus the broken line is placed 25% below the solid line which defines possible toxicity.
- If the predetoxification plasma level is below the broken line described above, there is minimal risk of hepatic toxicity and acetylcysteine treatment can be discontinued.
ACETAMINOPHEN ASSAY METHODOLOGY
Assay procedures most suitable for determining acetaminophen concentrations utilize high pressure liquid chromatography (HPLC) or gas liquid chromatography (GLC). The assay should measure only parent acetaminophen and not conjugated. The assay procedures listed below fulfill this requirement:
SELECTED TECHNIQUES (NONINCLUSIVE)
- 1. Blair D, Rumack BH. Clin Chem. 1977; 23(4): 743-745.
- 2. Howie D, Andriaenssens Pl, Prescott LF. J Pharm Pharmacol 1977; 29(4): 235-237.
- 3.Prescott LF. J Pharm Pharmacol 1971; 23(10): 807-808.
- 4. Glynn JP, Kendal SE. Lancet 1975; 1(May 17): 1147-1148.
Supportive Treatment of Acetaminophen Overdose
- Maintain fluid and electrolyte balance based on clinical evaluation of state of hydration and serum electrolytes.
- Treat as necessary for hypoglycemia.
- Administer vitamin K1 if prothrombin time ratio exceeds 1.5 or fresh frozen plasma if the prothrombin time ratio exceeds 3.0.
- Diuretics and forced diuresis should be avoided.
DOSAGE GUIDE AND PREPARATION
Doses in relation to body weight are:
Loading Dose of MUCOMYST® (acetylcysteine)**
|mL of 20%|
|Total mL of|
|** If patient weighs less than 20 kg (usually patients younger than 6 years), calculate the dose of MUCOMYST. Each mL of 20% MUCOMYST contains 200 mg of acetylcysteine. The loading dose is 140 mg per kilogram of body weight. The maintenance dose is 70 mg/kg. Three (3) mL of diluent are added to each mL of 20% MUCOMYST. Do not decrease the proportion of diluent.|
|mL of 20%|
|Total mL of|
|30-39||66-86||3||15 ||45 ||60|
Estimating Potential for Hepatoxicity
The following nomogram has been developed to estimate the probability that plasma levels in relation to intervals post ingestion will result in hepatoxocity.
Adapted from Rumack and Matthews, Pediatrics 1975; 55: 871-876.