Acetylcysteine (Page 2 of 4)

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.

ADVERSE REACTIONS

Adverse effects have included stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction. Clinically overt acetylcysteine induced bronchospasm occurs infrequently and unpredictably even in patients with asthmatic bronchitis or bronchitis complicating bronchial asthma.

Acquired sensitization to acetylcysteine have 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.

DOSAGE AND ADMINISTRATION

General

Acetylcysteine Solution 10% and 20% is available in glass vials containing 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, or Sterile Water for Inhalation. The 10% solution may be used undiluted.

Storage of Opened Vials

This product 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 acetylcysteine (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.

Direct Instillation

When used by direct instillation, 1 to 2 mL of a 10% or 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.

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 to 4 mL of the 10% solution every 1 to 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 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

Materials

Acetylcysteine 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 material may come into contact with acetylcysteine 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.

Nebulizing Gases

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 usual precautions in patients with severe respiratory disease and CO₂ retention.

Apparatus

Acetylcysteine 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 acetylcysteine 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 acetylcysteine 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 acetylcysteine because their output is generally too small. Also, some hand-operated nebulizers deliver particles that are larger than optimum for inhalation therapy.

Acetylcysteine 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 acetylcysteine 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.

Prolonged Nebulization

When three-fourths of the initial volume of acetylcysteine solution has 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.

Compatibility

The physical and chemical compatibility of acetylcysteine with certain other drugs that might be concomitantly administered by nebulization, direct instillation, or topical application, has been studied.

Acetylcysteine 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 acetylcysteine 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.

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 admixtures 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 acetylcysteine solutions to volume of test solutions.
IN VITRO COMPATIBILITY1 TESTS OF ACETYLCYSTEINE
			RATIO TESTED6
PRODUCT AND/OR AGENT		COMPATIBILITY RATING	ACETYL- CYSTEINE	PRODUCT OR AGENT
ANESTHETIC, GAS
Halothane		Compatible	20%	Infinite
Nitrous Oxide		Compatible	20%	Infinite
ANESTHETIC, LOCAL
Cocaine HCl		Compatible	10%	5%
Lidocaine HCl		Compatible	10%	2%
Tetracaine HCl		Compatible	10%	1%
ANTIBACTERIALS (A parenteral form of each antibiotic was used)
Bacitracin2.3 (mix and use at once)		Compatible	10%	5,000 U/mL
Chloramonenicol Sodium Succinate		Compatible	20%	20 mg/mL
Carbenicillin Disodium2 (mix and use at once)		Compatible	10%	125 mg/mL
Gentamicin Sulfate2		Compatible	10%	20 mg/mL
Kanamycin Sulfate2 (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 (mix and use at once)		Compatible Compatible	10% 10%	25,000 U/mL 100,000 U/mL
Polymyxin B Sulfate2		Compatible	10%	50,000 U/mL
Cephalothin Sodium		Compatible	10%	110 mg/mL
Colistimethate Sodium2 (mix and use at once)		Compatible	10%	37.5 mg/mL
Vancomycin HCl2		Compatible	10%	25 mg/mL
Amphotercin B		Incompatible	4%-15%	1-4 mg/mL
Chlortetracycline HCl2		Incompatible	10%	12.5 mg/mL
Erythromycin Lactobionate		Incompatible	10%	15 mg/mL
Oxytetracycline HCl		Incompatible	10%	12.5 mL
Ampicillin Sodium		Incompatible	10%	50 mg/mL
Tetracycline HCl		Incompatible	10%	12.5 mg/mL
BRONCHODILATORS
Isoproterenol HCl2		Compatible	3%	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% (2 parts)	(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%	.25%
Phenylephrine HCl		Compatible	13.3% (2 parts)	.17% (1 part)
ENZYMES
Chymotrypsin		Incompatible	5%	400 γ /mL
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)

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