Acetylcysteine Solution

Acetylcysteine Solution Manufacturers

• Roxane Laboratories, Inc.
  

  ×

  Acetylcysteine Solution | Roxane Laboratories, Inc.

  

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  DOSAGE AND ADMINISTRATION General

  Acetylcysteine Solution, USP is available in rubber stoppered glass vials containing 10 mL or 30 mL. The 20% solution may be diluted to a lesser concentration with either Sodium Chloride Injection, Sodium Chloride for Inhalation, Sterile Water for Injection, or Sterile Water for Inhalation. 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 for inhalation only within 96 hours.

  Nebulization — Face Mask, Mouthpiece, Tracheostomy: When nebulized into a face mask, mouthpiece, 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 three to four 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% 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.

  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 solution 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 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 solution 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 Da Vilbiss (The Da Vilbiss Co., Somerset, PA) and the Bennett Twin-Jet Nebulizer (Puritan Bennett Corp., Oak at 13th, Kansas City, MO).

  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 solution 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 mouthpieces, 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, USP (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 solutions 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.

  DOSAGE AND ADMINISTRATION General

  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 solution. The following procedures are recommended:

  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 predetoxificaton acetaminophen plasma assay and for 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 acetylcysteine for oral administration as described in the specific Dosage Guide and Preparation table.) Determine the subsequent action based on predetoxification plasma acetaminophen information. Choose ONE of the following four courses of therapy. Predetoxification plasma acetaminophen level is clearly in 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 acetominophen level could not be obtained:   Proceed as in A. Predetoxification acetominophen level is clearly in the nontoxic range (beneath the dashed line on the nomogram) and you know that acetominophen overdose occurred at least 4 hours before the predetoxification acetaminophen plasma assays:   Discontinue administration of acetylcysteine. Predetoxification acetominophen level was in the nontoxic 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 wether or not the full 17-dose detoxification treatment is necessary. If the patient vomits any oral dose within 1 hour of administration, repeat that dose. 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 Acetylcysteine Solution 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. ACETYLCYSTEINE SOLUTION 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 FOUR HOURS FOLLOWING AN ACUTE OVERDOSE, ARE ESSENTIAL IN ASSESSING THE POTENTIAL RISK OF HEPATOTOXICITY. IF AN ASSAY FOR ACETAMINOPHEN CANNOT BE OBTAINED, IT IS NECESSARY TO ASSUME THAT THE 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 mcg/mL at 4 hours with 50 mcg/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):

  HPLC
  1.     Blair D and Rumack BH, Clin Chem 1977, 23(4):743–745 (April).
  2.     Howie D, Andriaenssens PI and Prescott LF, J Pharm Pharmacol 1977, 29(4):235–237 (April).

  GLC
  3.     Prescott LF, J Pharm Pharmacol 1971, 23(10):807–808 (October).

  Colorimetric
  4.     Glynn JP and Kendal SE, Lancet 1975,1 (May 17):1147–1148.

  Supportive Treatment of Acetaminophen Overdosage:

  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.

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  More Info
• Physicians Total Care, Inc.
  

  ×

  Acetylcysteine Solution | Physicians Total Care, Inc.

  

  ---

  DOSAGE AND ADMINISTRATION General

  Acetylcysteine Solution, USP is available in rubber stoppered glass vials containing 10 mL or 30 mL. The 20% solution may be diluted to a lesser concentration with either Sodium Chloride Injection, Sodium Chloride for Inhalation, Sterile Water for Injection, or Sterile Water for Inhalation. 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 for inhalation only within 96 hours.

  Nebulization — Face Mask, Mouthpiece, Tracheostomy: When nebulized into a face mask, mouthpiece, 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 three to four 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% 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.

  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 solution 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 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 solution 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 Da Vilbiss (The Da Vilbiss Co., Somerset, PA) and the Bennett Twin-Jet Nebulizer (Puritan Bennett Corp., Oak at 13th, Kansas City, MO).

  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 solution 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 mouthpieces, 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, USP (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 solutions 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.

  DOSAGE AND ADMINISTRATION General

  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 solution. The following procedures are recommended:

  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 predetoxificaton acetaminophen plasma assay and for 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 acetylcysteine for oral administration as described in the specific Dosage Guide and Preparation table.) Determine the subsequent action based on predetoxification plasma acetaminophen information. Choose ONE of the following four courses of therapy. Predetoxification plasma acetaminophen level is clearly in 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 acetominophen level could not be obtained:   Proceed as in A. Predetoxification acetominophen level is clearly in the nontoxic range (beneath the dashed line on the nomogram) and you know that acetominophen overdose occurred at least 4 hours before the predetoxification acetaminophen plasma assays:   Discontinue administration of acetylcysteine. Predetoxification acetominophen level was in the nontoxic 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 wether or not the full 17-dose detoxification treatment is necessary. If the patient vomits any oral dose within 1 hour of administration, repeat that dose. 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 Acetylcysteine Solution 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. ACETYLCYSTEINE SOLUTION 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 FOUR HOURS FOLLOWING AN ACUTE OVERDOSE, ARE ESSENTIAL IN ASSESSING THE POTENTIAL RISK OF HEPATOTOXICITY. IF AN ASSAY FOR ACETAMINOPHEN CANNOT BE OBTAINED, IT IS NECESSARY TO ASSUME THAT THE 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 mcg/mL at 4 hours with 50 mcg/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):

  HPLC
  1.     Blair D and Rumack BH, Clin Chem 1977, 23(4):743–745 (April).
  2.     Howie D, Andriaenssens PI and Prescott LF, J Pharm Pharmacol 1977, 29(4):235–237 (April).

  GLC
  3.     Prescott LF, J Pharm Pharmacol 1971, 23(10):807–808 (October).

  Colorimetric
  4.     Glynn JP and Kendal SE, Lancet 1975,1 (May 17):1147–1148.

  Supportive Treatment of Acetaminophen Overdosage:

  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.

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  More Info
• Hospira, Inc.
  

  ×

  Acetylcysteine Solution | Hospira, Inc.

  

  ---

  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)

  Acetylcysteine As An Antidote For Acetaminophen Overdose

  General

  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 drinking copious amounts 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 its effectiveness. 3. Draw blood for predetoxification acetaminophen plasma assay and for baseline SGOT, SGPT, bilirubin, prothrombin time, creatinine, BUN, blood sugar and electrolytes. 4. Administer the loading dose of acetylcysteine, 140 mg per kg of body weight. (Prepare acetylcysteine for oral administration as described in the Specific Dosage Guide and Preparation table.) 5. Determine subsequent action based on predetoxification plasma acetaminophen information. Choose ONE of the following four courses of therapy. A. 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 maintenence 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. B. Predetoxification acetaminophen level could not be obtained:
  Proceed as in A. C. Predetoxification acetaminophen level is clearly in the nontoxic range (beneath the dashed line on the nomogram) and you know that acetaminophen overdose occured at least 4 hours before the predetoxification acetaminophen plasma assays:
  Discontinue administration of acetylcysteine. D. 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. 6. If the patient vomits any oral dose within 1 hour of administration, repeat that 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.

  Preparation of 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.

  ACETYLCYSTEINE 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 FOUR HOURS FOLLOWING AN ACUTE OVERDOSE, ARE ESSENTIAL IN ASSESSING THE POTENTIAL RISK OF HEPATOTOXICITY. IF AN ASSAY FOR ACETAMINOPHEN CANNOT BE OBTAINED, IT IS NECESSARY TO ASSUME THAT THE 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 solid line connecting 200 mcg/mL at 4 hours with 50 mcg/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.) 2. 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. 3. 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 (non-inclusive)

  HPLC:

  1. Blair, D and Rumack, BH, Clin Chem. 1977; 23(4):743−745.
  2. Howie, D, Andriaenssens, Pl, Prescott, LF. J Pharm Pharmacol 1977; 29(4):235−237.

  GLC:

  3. Prescott, LF. J Pharm Pharmacol 1971; 23(10);807−808.

  Colorimetric:

  4. Glynn, JP and Kendal, SE. Lancet 1975; 1(May 17):1147-1148.

  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 K 1 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 on preceding page). DOSAGE GUIDE AND PREPARATION **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 per kilogram 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.

  Doses in relation to body weight are:

  Loading Dose of Acetylcysteine**

  Grams

  mL of 20%

  mL of

  Total mL of

  Body Weight

  Acetylcysteine

  Acetylcysteine

  Diluent

  5% Solution

        (kg)

     (lb)

  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**

  (kg)

  (lb)

  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

  Estimating Potential for Hepatotoxicity:

  The following nomogram has been developed to estimate the probability that plasma levels in relation to intervals post ingestion will result in hepatotoxicity.

  Adapted from Rumack and Matthews, Pediatrics 1975; 55:871−876.

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  Acetylcysteine Solution | Fresenius Kabi Usa, Llc

  

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  General

  Acetylcysteine 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 Injection, Sodium Chloride Inhalation Solution, Sterile Water for Injection, or Sterile Water for Inhalation. 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 for inhalation, 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 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% 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.

  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, two or 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

  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 materials 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 the 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 the 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 in 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 have been nebulized, a quantity of Sterile Water for Injection, USP (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 solutions 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.

  IN VITRO COMPATIBILITY1 TESTS OF ACETYLCYSTEINE

  PRODUCT AND/OR

  AGENT

  COMPATIBILITY

  RATING

  RATIO TESTED6

  ACETYLCYSTEINE

  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

  Chloramphenicol 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

  10%

  25,000 U/mL

     

  Compatible

  10% 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

  Amphotericin B

  Incompatible

  4% to 15%

  1 to 4 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)

  0.33% (1 part)

  Isoetharine HCl

  Compatible

  13.3% (2 parts)

  (1 part)

  Epinephrine HCl

  Compatible

  13.3% (2 parts)

  0.33% (1 part)

  CONTRAST MEDIA

  Iodized Oil

  Incompatible

  20%/20 mL

  40%/10 mL

  DECONGESTANTS

  Phenylephrine HCl2

  Compatible

  3.0%

  0.25%

  Phenylephrine HCl

  Compatible

  13.3% (2 parts)

  0.17% (1 part)

  ENZYMES

  Chymotrypsin

  Incompatible

  5%

  400 γ/mL

  Trypsin

  Incompatible

  5%

  400 γ/mL

  SOLVENTS

  Alcohol

  Compatible

  12%

  10% to 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)

  The rating, Incompatible, is based on the formulation 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.

  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.

  A strong odor developed after storage for 24 hours at room temperature.

  The admixture was a slightly darker shade of yellow than a control solution of the PRODUCT AND/OR AGENT.

  A light tan color developed after storage for 24 hours at room temperature.

  Entries are final concentrations. Values in parentheses relate volumes of acetylcysteine solutions to volume of test solutions.

   

  General

  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:

  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 amounts 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 acetylcysteine for oral administration as described in the Dosage Guide and Preparation table).

  Determine subsequent action based on predetoxification plasma acetaminophen information. Choose ONE of the following four courses of therapy.

  A. 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.

  B. Predetoxification acetaminophen level could not be obtained: Proceed as in A.

  C. Predetoxification acetaminophen level is clearly in the non-toxic 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.

  D. 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 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.

  If the patient vomits an oral dose within 1 hour of administration, repeat that dose.

  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 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.

  ACETYLCYSTEINE 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 mcg/mL at least 4 hours with 50 mcg/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 (NON INCLUSIVE)

  HPLC:

  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. GLC

  3. Prescott LF. J. Pharm Pharmacol, 1971; 23(10):807-808. Colorimetric

  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 Acetylcysteine**

  Body Weight

  Grams
  Acetylcysteine

  mL of 20%
  Acetylcysteine

  mL of
  Diluent

  Total mL of
  5% Solution

  (kg)

  (lb)

  100 to 109

  220 to 240

  15

  75

  225

  300

  90 to 99

  198 to 218

  14

  70

  210

  280

  80 to 89

  176 to 196

  13

  65

  195

  260

  70 to 79

  154 to 174

  11

  55

  165

  220

  60 to 69

  132 to 152

  10

  50

  150

  200

  50 to 59

  110 to 130

  8

  40

  120

  160

  40 to 49

  88 to 108

  7

  35

  105

  140

  30 to 39

  66 to 86

  6

  30

  90

  120

  20 to 29

  44 to 64

  4

  20

  60

  80

  Maintenance Dose**

  (kg)

  (lb)

  100 to 109

  220 to 240

  7.5

  37

  113

  150

  90 to 99

  198 to 218

  7

  35

  105

  140

  80 to 89

  176 to 196

  6.5

  33

  97

  130

  70 to 79

  154 to 174

  5.5

  28

  82

  110

  60 to 69

  132 to 152

  5

  25

  75

  100

  50 to 59

  110 to 130

  4

  20

  60

  80

  40 to 49

  88 to 108

  3.5

  18

  52

  70

  30 to 39

  66 to 86

  3

  15

  45

  60

  20 to 29

  44 to 64

  2

  10

  30

  40

  **If patient weighs less than 20 kg (usually patients younger than 6 years), calculate the doses of Acetylcysteine. Each mL of 20% Acetylcysteine 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% Acetylcysteine Solution. Do not decrease the proportion of diluent.

  Estimating Potential for Hepatotoxicity

  The following nomogram has been developed to estimate the probability that plasma levels in relation to intervals post ingestion will result in hepatotoxicity.

  Adapted from Rumack and Matthews, Pediatrics 1975; 55:871−876.

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