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Acetylcysteine, Acetylcysteine Lysine(Local, Systemic) (Monograph)

Brand names: Acetadote ; , Legubeti
Drug class: Acetaminophen antidote

Medically reviewed by Drugs.com on Jun 10, 2024. Written by ASHP.

Introduction

Antidote for acetaminophen overdosage; mucolytic agent and sulfhydryl donor.102 108 120

Uses for Acetylcysteine, Acetylcysteine Lysine(Local, Systemic)

Antidote for Acetaminophen Overdosage

Treatment of acetaminophen overdosage following acute ingestion or repeated supratherapeutic ingestion.102 103 108 IV acetylcysteine designated an orphan drug by FDA for this use.121 Optimal if given within 8 hours of acute acetaminophen ingestion;109 may be effective when given ≥24 hours after ingestion.105 106

Mucolytic Uses

Adjunctive treatment for patients with abnormal, viscid, or inspissated mucous secretions associated with conditions such as acute and chronic bronchopulmonary disorders (e.g., pneumonia, bronchitis, emphysema, tracheobronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis, primary amyloidosis of the lung); atelectasis caused by mucus obstruction; pulmonary complications of cystic fibrosis; pulmonary complications of surgery; and post-traumatic chest conditions.102

Used during anesthesia and in the preparation of patients for bronchograms, bronchospirometry, bronchial wedge catheterization, and other diagnostic bronchial studies.102

Tracheostomy care.102

Prevention of Nephropathy Associated with Radiographic Contrast Media

Has been used to prevent radiographic contrast media-induced nephropathy [off-label].100 101 110 111 112 113 114 116 117 122 123 124 125 126 127 Efficacy for this indication not supported by the results of large, randomized clinical trials;126 127 use not recommended in some current clinical guidelines.115 130 131

Acetylcysteine, Acetylcysteine Lysine(Local, Systemic) Dosage and Administration

General

Pretreatment Screening

Patient Monitoring

Administration

Administer orally (as a solution) or by IV infusion as an antidote for acetaminophen overdosage; administer by oral inhalation or intracheal instillation for mucolytic uses.102 103 108

Has been administered orally100 110 117 or IV110 117 for prevention of radiographic contrast media-induced nephropathy [off-label].

Oral Administration

May administer as a 5% solution for acetaminophen overdose.102 To prepare the 5% solution, dilute commercially available 20% solution 1:3 with diet soft drink.102

Alternatively, may use oral solution prepared from commercially available packets containing 500 mg or 2.5 g of acetylcysteine (available as acetylcysteine lysine [Legubeti]).103 To prepare oral solution, dissolve the appropriate number of packets in the volume of caffeine-free diet cola or other diet soft drink, as indicated in dosing tables provided in the prescribing information.103 The Legubeti preparation is for oral administration only and should not be used for nebulization or intratracheal instillation.103

May administer via duodenal or nasoduodenal tube if persistently unable to retain orally administered drug; also may consider IV formulation.102 103

IV Administration

Injection concentrate must be diluted prior to IV administration.108

Acetylcysteine solution for inhalation or oral administration should not be administered by injection.102

Dilution

Dilute dose with an appropriate volume of 5% dextrose injection, 0.45% sodium chloride injection, or sterile water for injection(see Table 1).108

Adjust total volume for patients who weigh <40 kg (see Table 1) or for those requiring fluid restriction.108 In patients weighing ≤20 kg, the recommended volume of diluent is 3, 7, and 14 mL/kg for the loading, second, and third doses, respectively.108

Table 1. Recommended Volumes of Diluent for Dilution of IV Acetylcysteine Doses108

Volume of Diluent for Indicated Dose

Patient’s Weight (kg)

Loading Dose

First Maintenance Dose

Second Maintenance Dose

≥41

200 mL

500 mL

1 L

21 to 40

100 mL

250 mL

500 mL

20

60 mL

140 mL

280 mL

15

45 mL

105 mL

210 mL

10

30 mL

70 mL

140 mL

5

15 mL

35 mL

70 mL

Dilution in the 3 compatible diluents results in different osmolarity of the solution for IV administration (see Table 2).108 Adjust osmolarity to a physiologically safe level (generally ≥150 mOsmol/L in pediatric patients).108

Table 2. Examples of Acetylcysteine Concentration and Osmolarity in Different Diluents108

Acetylcysteine Concentration

Osmolarity in Sterile Water for Injection

Osmolarity in 0.45% Sodium Chloride Injection

Osmolarity in 5% Dextrose Injection

7 mg/mL

91 mOsmol/L

245 mOsm/L

343 mOsm/L

24 mg/mL

312 mOsmol/L

466 mOsmol/L

564 mOsmol/L

Rate of Administration

Loading dose: Infuse over 1 hour.108 109

First maintenance dose: Infuse over 4 hours.108

Second maintenance dose: Infuse over 16 hours.108

Oral Inhalation and Intratracheal Instillation

For use as a mucolytic agent, administer 20% acetylcysteine solution undiluted or dilute with sodium chloride injection, sodium chloride inhalation solution, sterile water for injection, or sterile water for inhalation solution.102

May use 10% acetylcysteine solution undiluted.102

Dosage

Pediatric Patients

Antidote for Acetaminophen Overdosage
Oral

Loading dose: 140 mg/kg, administered as soon as possible.102 103 Maintenance dosage, if indicated: 70 mg/kg every 4 hours for 17 doses.102 103

If patient vomits a loading or maintenance dose within 1 hour of administration, repeat the dose.102 103

IV

Loading dose: 150 mg/kg, administered as soon as possible. 108

First maintenance dose: 50 mg/kg. 108

Second maintenance dose: 100 mg/kg. 108

Recommended dosage for patients weighing <5 kg not studied.108

Mucolytic Uses
Nebulization

Face mask, mouthpiece, or tracheostomy: 3–5 mL of the 20% solution or 6–10 mL of the 10% solution 3 or 4 times daily; alternatively, 1–10 mL of the 20% solution or 2–20 mL of the 10% solution every 2–6 hours.102

Tent or croupette: Volume of acetylcysteine solution should be sufficient to maintain a very heavy mist in the tent or croupette for the desired period; maintenance of heavy mist may require up to 300 mL of the 10 or 20% solution for a single, continuous treatment.102 Administer intermittently or for continuous prolonged periods.102

Direct Instillation

1–2 mL of a 10–20% solution as often as every hour.102

Intratracheal Instillation

Instillation through a percutaneous intratracheal catheter: 1–2 mL of the 20% solution or 2–4 mL of the 10% solution every 1–4 hours via a syringe attached to the catheter.102

Instillation through a catheter into the trachea: 2–5 mL of the 20% solution via a syringe attached to the catheter.102

Diagnostic Bronchial Studies
Nebulization

2 or 3 doses of 1–2 mL of the 20% solution or 2–4 mL of the 10% solution prior to the procedure.102

Intratracheal Instillation

2 or 3 doses of 1–2 mL of the 20% solution or 2–4 mL of the 10% solution prior to the procedure.102

Tracheostomy Care
Intratracheal Instillation

1–2 mL of a 10–20% solution into the tracheostomy every 1–4 hours.102

Adults

Antidote for Acetaminophen Overdosage
Oral

Loading dose: 140 mg/kg, administered as soon as possible.102 103 Maintenance dosage, if indicated: 70 mg/kg every 4 hours for 17 doses.102 103

If patient vomits a loading or maintenance dose within 1 hour of administration, repeat the dose.102 103

IV

Loading dose: 150 mg/kg, administered as soon as possible.108

First maintenance dose: 50 mg/kg.108

Second maintenance dose: 100 mg/kg.108

Limited information available regarding dosing requirements of patients weighing >100 kg.108

Mucolytic Uses
Nebulization

Face mask, mouthpiece, tracheostomy: 3–5 mL of the 20% solution or 6–10 mL of the 10% solution 3 or 4 times daily; alternatively, 1–10 mL of the 20% solution or 2–20 mL of the 10% solution every 2–6 hours.102

Tent or croupette: Volume of acetylcysteine solution should be sufficient to maintain a very heavy mist in the tent or croupette for the desired period; maintenance of heavy mist may require up to 300 mL of the 10 or 20% solution for a single, continuous treatment.102 Administer intermittently or for continuous prolonged periods.102

Direct Instillation

1–2 mL of a 10–20% solution as often as every hour.102

Intratracheal Instillation

Instillation through a percutaneous intratracheal catheter: 1–2 mL of the 20% solution or 2–4 mL of the 10% solution every 1–4 hours via a syringe attached to the catheter.102

Instillation through a catheter into the trachea: 2–5 mL of the 20% solution via a syringe attached to the catheter.102

Diagnostic Bronchial Studies
Nebulization

For diagnostic bronchial studies: 2 or 3 doses of 1–2 mL of the 20% solution or 2–4 mL of the 10% solution prior to the procedure.102

Intratracheal Instillation

For diagnostic bronchial studies: 2 or 3 doses of 1–2 mL of the 20% solution or 2–4 mL of the 10% solution prior to the procedure.102

Tracheostomy Care
Intratracheal Instillation

1–2 mL of a 10–20% solution into the tracheostomy every 1–4 hours.102

Prevention of Nephropathy Associated with Radiographic Contrast Media† [off-label]
Oral

600 mg twice daily, given the day before and the day of contrast media administration (total of 4 doses), has been used.100 110 117 122 Other dosage regimens have been investigated.110 117 126 127

Special Populations

Hepatic Impairment

Limited data in hepatic impairment suggest no clinically meaningful effects on acetylcysteine pharmacokinetics.108 No specific dosage recommendations for hepatic impairment.108

Renal Impairment

No specific dosage recommendations for renal impairment;102 108 hemodialysis may remove some acetylcysteine.108

Cautions for Acetylcysteine, Acetylcysteine Lysine(Local, Systemic)

Contraindications

Warnings/Precautions

Encephalopathy Due to Hepatic Failure

If encephalopathy resulting from hepatic failure occurs during oral acetylcysteine therapy, discontinue the drug to avoid further administration of nitrogenous substances.102

No data indicating that acetylcysteine influences hepatic failure; however, this remains a theoretical possibility.102

Respiratory Effects

An increased volume of liquefied bronchial secretions may develop following oral inhalation or intratracheal instillation; airway may become occluded.102 If cough is inadequate to maintain an open airway, institute mechanical suction or endotracheal aspiration (with or without bronchoscopy).102

Irritation of tracheal and bronchial tracts and hemoptysis have occurred following administration; however, such findings are not uncommon in patients with bronchopulmonary disease and a causal relationship not established.102

Chest tightness and bronchoconstriction reported.102 Clinically overt acetylcysteine-induced bronchospasm occurs rarely and unpredictably, even in patients with asthmatic bronchitis or bronchitis complicating bronchial asthma.102 Occasionally, patients receiving oral inhalation of acetylcysteine develop increased airway obstruction of varying and unpredictable severity.102 Patients who have had such reactions to previous therapy with acetylcysteine may not react during subsequent therapy with the drug, and patients who have had inhalation treatments with acetylcysteine without incident may react to subsequent therapy.102

If bronchospasm occurs, give a bronchodilator by nebulization.102 If bronchospasm progresses, discontinue acetylcysteine immediately.102 When administered by IV infusion, use with caution in patients with asthma or history of bronchospasm.108

Hypersensitivity Reactions

Serious hypersensitivity reactions (e.g., rash, hypotension, wheezing, dyspnea), including death in a patient with asthma, reported in patients receiving IV acetylcysteine.108

Acute flushing and erythema also reported; generally occur 30–60 minutes after initiation of infusion and resolve despite continued infusion.108 Reactions to acetylcysteine that involve symptoms other than flushing and erythema should be considered anaphylactoid reactions and treated accordingly.108

If a severe hypersensitivity reaction occurs during IV therapy, immediately discontinue IV acetylcysteine and initiate appropriate treatment.108 If less severe hypersensitivity reactions occur, manage according to severity; management may include temporary interruption of infusion and/or administration of antihistamines.108

Once treatment of hypersensitivity reaction has been initiated, carefully reinstitute IV acetylcysteine.108 If hypersensitivity reaction recurs or increases in severity, discontinue IV acetylcysteine and consider alternative management.108 Closely monitor patients with asthma during initiation of and throughout IV therapy.108

Generalized urticaria reported rarely in patients receiving oral acetylcysteine for acetaminophen overdosage.102 If urticaria or other allergic symptoms occur during oral therapy, discontinue the drug unless it is considered essential and allergic symptoms can be otherwise controlled.102

Acquired sensitization to acetylcysteine reported rarely.102 Sensitization not confirmed by patch testing.102 Sensitization to acetylcysteine and dermal eruptions reported by several inhalation therapists after frequent and extended exposure to the drug.102

GI Effects

Oral administration may result in vomiting or may aggravate vomiting associated with acetaminophen overdosage.102 Dilution of acetylcysteine prior to oral administration may minimize effects.102

Evaluate patients at risk of gastric hemorrhage (e.g., those with esophageal varices or peptic ulcers) with regard to relative risks of upper GI hemorrhage and acetaminophen-induced hepatotoxicity; provide acetylcysteine treatment accordingly.102

Fluid Overload

IV administration of acetylcysteine can cause fluid overload, possibly resulting in hyponatremia, seizures, and death.108 To avoid fluid overload, follow recommendations for dilution and reduce the volume of diluent as needed.108

Nebulization Administration Precautions

A slight disagreeable odor that tends to become unnoticeable and stickiness on the face with use of a face mask (easily removed with water) can occur with administration by nebulization.102

An increased concentration of the drug in the nebulizer due to evaporation of the solvent occurs with continued nebulization of acetylcysteine solution with a dry gas.102 If extreme concentration impedes nebulization and efficient delivery of the drug, dilute the nebulizing solution with appropriate amounts of sterile water for injection as concentration occurs to resolve this problem.102

Specific Populations

Pregnancy

Limited published case reports and case series of pregnant women exposed to acetylcysteine during various trimesters insufficient to inform any drug-associated risk.108 Delaying treatment of acetaminophen overdose may increase risk of maternal or fetal morbidity and mortality.108

Lactation

Not known whether acetylcysteine is distributed into human milk;102 108 effects on breast-fed infant or on milk production also not known.108 Consider the developmental and health benefits of breast-feeding along with the mother’s need for acetylcysteine and any potential adverse effects on the breast-fed child from acetylcysteine or from the underlying maternal condition.108 Use acetylcysteine with caution in nursing women.102

Based on pharmacokinetic data, acetylcysteine should be nearly completely cleared 30 hours after IV administration.108 Breast-feeding women may consider pumping and discarding their milk for 30 hours after administration.108

Pediatric Use

Efficacy of IV acetylcysteine as an antidote for acetaminophen overdosage appears to be similar to that in adults.108 Safety and efficacy of IV acetylcysteine in pediatric patients not established by adequate and well-controlled studies; use of IV acetylcysteine as an antidote for acetaminophen overdosage in pediatric patients ≥5 kg is based on clinical practice.108

Geriatric Use

Insufficient experience with IV acetylcysteine in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.108

Common Adverse Effects

Oral administration: Nausea, vomiting, other GI symptoms.102

IV administration (reported in >2% of patients): Rash, urticaria/facial flushing, pruritus.108

Oral inhalation/intratracheal instillation: Stomatitis, nausea, vomiting, fever, rhinorrhea, drowsiness, clamminess, chest tightness, bronchoconstriction.102

Drug Interactions

Activated Charcoal

Possible interference with absorption of oral acetylcysteine;102 119 however, usual dosage of acetylcysteine is appropriate in patients given activated charcoal (higher dosages not necessary).105 106 Manufacturer recommends that if activated charcoal has been administered, lavage should be performed before administering oral acetylcysteine treatment.102

Acetylcysteine, Acetylcysteine Lysine(Local, Systemic) Pharmacokinetics

Absorption

Bioavailability

Absorbed following oral administration, with peak plasma concentrations achieved within 1–2 hours.119

Distribution

Extent

Crosses the placenta.108

Plasma Protein Binding

50–87%.108 119

Elimination

Metabolism

Deacetylated to cysteine and oxidized to yield diacetylcysteine.102 108 Cysteine is further metabolized to form glutathione and other metabolites.108

Elimination Route

Principally (70%) nonrenal.108 119

Half-life

6.25 hours after oral administration.119

5.6 hours after IV administration in adults.108

Special Populations

Following IV administration of acetylcysteine in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), or severe (Child-Pugh class C) hepatic impairment, mean elimination half-life is increased by 80% compared with normal subjects.108 Mean clearance is decreased by 30% and systemic exposure increased 1.6-fold in subjects with hepatic impairment compared to subjects with normal hepatic function.108 These changes are not considered clinically meaningful.108

Hemodialysis may remove some of total acetylcysteine.108

Stability

Storage

Oral, Oral Inhalation, Intratracheal Instillation

Solution

20–25°C (excursions permitted to 15–30°C).102 Use diluted solutions within 1 hour.102 Store undiluted solution in opened vials in refrigerator; use within 96 hours.102 Presence of a light purple color in the solution does not appreciably affect drug potency.102 Do not store admixtures.102

Packets for Oral Solution

20–25°C (excursions permitted to 15–30°C).103 Use prepared solution within 1 hour after preparation.103

Parenteral

Injection Concentrate for IV Infusion

20–25°C.108

Presence of light pink to purple color in diluted solution does not affect the quality of the product.108

Do not use previously opened vials for IV administration.108

Following dilution with 5% dextrose, 0.45% sodium chloride, or sterile water for injection, stable at controlled room temperature for 24 hours.108

Actions

Advice to Patients

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Acetylcysteine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation, Intratracheal Instillation, and Oral

Solution

100 mg/mL (10%)*

Acetylcysteine Solution

200 mg/mL (20%)*

Acetylcysteine Solution

Parenteral

For injection concentrate, for IV infusion

200 mg/mL

Acetadote

Cumberland

Acetylcysteine Lysine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

For oral solution

500 mg (of acetylcysteine)

Legubeti

Galephar

2.5 g (of acetylcysteine)

Legubeti

Galephar

AHFS DI Essentials™. © Copyright 2024, Selected Revisions June 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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101. Safirstein R, Andrade L, Vieira JM. Acetylcysteine and nephrotoxic effects of radiographic contrast agents—a new use for an old drug. N Engl J Med. 2000; 343: 210-2. http://www.ncbi.nlm.nih.gov/pubmed/10900284?dopt=AbstractPlus

102. Fresenius Kabi. Acetylcysteine solution USP prescribing information. Lake Zurich, IL; 2018 Sep.

103. Galephar Pharmaceutical Research Inc. Legubeti (acetylcysteine) for oral solution prescribing information. Puerto Rico; 2024 Feb

105. Acetaminophen (paracetamol). In: Ellenhorn MJ, Schonwald S, Ordog G et al., eds. Ellenhorn’s medical toxicology: diagnosis and treatment of human poisoning. 2nd ed. Baltimore, MD: Williams & Wilkens; 1997:180-95.

106. Zed PJ, Krenzelok EP. Treatment of acetaminophen overdose. Am J Health-Syst Pharm. 1999; 56:1081-93. http://www.ncbi.nlm.nih.gov/pubmed/10385455?dopt=AbstractPlus

108. Cumberland Pharmaceuticals. Acetadote (acetylcysteine) injection prescribing information. Nashville, TN; 2021 Oct.

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110. Pannu N, Wiebe N, Tonelli M et al. Prophylaxis strategies for contrast-induced nephropathy. JAMA. 2006; 295:2765-79. http://www.ncbi.nlm.nih.gov/pubmed/16788132?dopt=AbstractPlus

111. Coyle LC, Rodriguez A, Jeschke RE et al. Acetylcysteine In Diabetes (AID): a randomized study of acetylcysteine for the prevention of contrast nephropathy in diabetics. Am Heart J. 2006; 151:1032.e9-12.

112. Carbonell N, Blasco M, Sanjuán R et al. Intravenous N-acetylcysteine for preventing contrast-induced nephropathy: A randomised trial. Int J Cardiol. 2007; 115:57-62 (Epub 2006 Jun 30). http://www.ncbi.nlm.nih.gov/pubmed/16814414?dopt=AbstractPlus

113. Bartholomew BA, Harjai KJ, Dukkipati S et al. Impact of nephropathy after percutaneous coronary intervention and a method for risk stratification. Am J Cardiol. 2004; 93:1515-9. http://www.ncbi.nlm.nih.gov/pubmed/15194023?dopt=AbstractPlus

114. McCullough PA, Adam A, Becker CR et al. Risk prediction of contrast-induced nephropathy. Am J Cardiol. 2006; 98 (suppl 6A):27K-36K.

115. McCullough PA, Stacul F, Davidson C et al. Overview. Am J Cardiol. 2006; 98 (suppl 6A):2K-4K.

116. Davidson C, Stacul F, McCullough PA et al. Contrast medium use. Am J Cardiol. 2006; 98 (suppl 6A):42K-58K. http://www.ncbi.nlm.nih.gov/pubmed/16949380?dopt=AbstractPlus

117. Stacul F, Adam A, Becker CR et al. Strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol. 2006; 98 (suppl 6A):59K-77K.

118. Daly FF, O’Malley GF, Heard K et al. Prospective evaluation of repeated supratherapeutic acetaminophen (paracetamol) ingestion. Ann Emerg Med. 2004; 44:393-400. http://www.ncbi.nlm.nih.gov/pubmed/15459622?dopt=AbstractPlus

119. Holdiness MR. Clinical pharmacokinetics of N-acetylcysteine. Clin Pharmacokinet. 1991; 20:123-34. http://www.ncbi.nlm.nih.gov/pubmed/2029805?dopt=AbstractPlus

120. Pedre B, Barayeu U, Ezeriņa D et al. The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species. Pharmacol Ther. 2021; 228:107916. http://www.ncbi.nlm.nih.gov/pubmed/34171332?dopt=AbstractPlus

121. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2023 Jul 19.

122. Magner K, Ilin JV, Clark EG et al. Meta-analytic techniques to assess the association between N-acetylcysteine and acute kidney injury after contrast administration: a systematic review and meta-analysis. JAMA Netw Open. 2022; 5:e2220671. http://www.ncbi.nlm.nih.gov/pubmed/35788669?dopt=AbstractPlus

123. Xu R, Tao A, Bai Y et al. Effectiveness of N-acetylcysteine for the prevention of contrast-induced nephropathy: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2016; 5:e003968. http://www.ncbi.nlm.nih.gov/pubmed/27663415?dopt=AbstractPlus

124. Giacoppo D, Gargiulo G, Buccheri S et al. Preventive strategies for contrast-induced acute kidney injury in patients undergoing percutaneous coronary procedures: evidence from a hierarchical bayesian network meta-analysis of 124 trials and 28 240 patients. Circ Cardiovasc Interv. 2017; 10:e004383. http://www.ncbi.nlm.nih.gov/pubmed/28487354?dopt=AbstractPlus

125. Walker H, Guthrie GD, Lambourg E et al. Systematic review and meta-analysis of prophylaxis use with intravenous contrast exposure to prevent contrast-induced nephropathy. Eur J Radiol. 2022; 153:110368.

126. Weisbord SD, Gallagher M, Jneid H et al. Outcomes after angiography with sodium bicarbonate and acetylcysteine. N Engl J Med. 2018; 378:603-14. http://www.ncbi.nlm.nih.gov/pubmed/29130810?dopt=AbstractPlus

127. ACT Investigators. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized Acetylcysteine for Contrast-induced nephropathy Trial (ACT). Circulation. 2011; 124:1250-9. http://www.ncbi.nlm.nih.gov/pubmed/21859972?dopt=AbstractPlus

128. Huang JW, Lahey B, Clarkin OJ et al. A systematic review of the effect of N-acetylcysteine on serum creatinine and cystatin C measurements. Kidney Int Rep. 2020; 6:396-403. http://www.ncbi.nlm.nih.gov/pubmed/33615065?dopt=AbstractPlus

129. Sandilands EA, Rees JMB, Raja K et al. Acetylcysteine has no mechanistic effect in patients at risk of contrast-induced nephropathy: a failure of academic clinical science. Clin Pharmacol Ther. 2022; 111:1222-38. http://www.ncbi.nlm.nih.gov/pubmed/35098531?dopt=AbstractPlus

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