Medications> Nephropathy>

INDICATIONS

• Adjuvant mucolytic therapy for patients with abnormal, viscid, or inspissated mucous secretions secondary to respiratory diseases such as emphysema, tuberculosis, bronchitis or for treatment of respiratory complications of cystic fibrosis and tracheostomy care. 

• Nephrotoxicity prophylaxis (focus of this module)
• Acetaminophen overdose

USUAL ADULT DOSING

• For nephrotoxicity prophylaxis in patients with chronic renal insufficiency (including persons with diabetes) before CT scan with non-ionic, low-osmolality contrast agent: 600 mg PO twice daily, given the day prior to and the day of administration of the contrast agent (total of 4 doses).
• Prevention of contrast-associated nephropathy in patients (including persons with diabetes) undergoing angioplasty: 1200 mg IV bolus before angioplasty followed by 1200 mg PO twice daily for the 48 hours following angioplasty

FORMS

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

DOSING IN SPECIAL POPULATIONS

• Usual dose

• Although there was a 3-fold increase in acetylcysteine plasma concentrations in patients with hepatic cirrhosis, no acetylcysteine dose reduction is recommended.

• Pregnancy risk category B. Does not cross the placenta and case report of pregnant patients receiving acetylcysteine to treat acetaminophen overdose have found acetylcysteine to be safe and effective.

• Avoid. It is not known if acetylcysteine is distributed into human milk.

ADVERSE DRUG REACTIONS

• Strong odor of "rotten eggs" can cause dygeusia in many patients. Dilute the solution prior to oral administration as recommended to help mask the odor.
• Gastrointestinal: diarrhea, nausea (2% to 7% ), vomiting (9% to 12% ).

• Acute flushing and erythema of the skin during infusion. No intervention is needed.
• Respiratory: bronchospasm and respiratory distress (with inhaled acetylcysteine). Use inhaled acetylcysteine with caution in patient with history of bronchospasm and asthma.
• Anaphylactoid reaction (0.1% to 19% ): generally occurs in the first hour of IV acetylcysteine bolus. Consider diphenhydramine and slowing the infusion over one hour.

• Neurologic: status epilepticus (association unclear)
• Cardiovascular: abnormal ECG, decreased cardiac function (association unclear)
• Dermatologic: pruritus and urticaria

DRUG INTERACTIONS

• Nitroglycerin: pharmacologic effect of nitrates may be increased. Use with close monitoring.
• Charcoal: may decrease the serum concentrations of acetylcysteine.

PHARMACOKINETIC

COMMENTS

• Patients with diabetic nephropathy are often subject to multiple diagnostic contrast studies (e.g. CT scan, cardiac catherization); in these patients, acetylcysteine should be considered to prevent contrast-associated nephropathy in addition to adequate hydration where possible, with careful monitoring of renal function afterwards (see diabetes and renal disease module).
• May be especially useful in patients who have problems with volume overload (i.e. comorbid congestive heart failure) and may not be good candidates for pre- and post-study hydration to prevent contrast-induced nephropathy.
• Incidence of contrast-induced nephropathy significantly reduced in patients with chronic renal insufficiency given acetylcysteine compared to placebo when given orally (2% vs 21%; Tepel).
• Also, effective in prevention of contrast-induced nephropathy following angioplasty when given intravenously (8% vs 15%; Marenzi).

Basis for Recommendations

• Marenzi G, Assanelli E, Marana I, et al. ; N-acetylcysteine and contrast-induced nephropathy in primary angioplasty. ; N Engl J Med ; 2006 ; Vol. 354 ; pp. 2773 ;
  PUBMED: 16807414
  Rating: Basis for recommendation
  Comments:In patients undergoing angioplasty (large contrast load) after acute myocardial infarction, lower incidence of nephrotoxicity (Scr increased >25% from baseline) was observed with high dose (1200 mg twice-daily) acetylcysteine group compared to standard dose (600 mg twice daily) group (15% vs. 8%, P<0.001).
  
  
• Tepel M, van der Giet M, Schwarzfeld C, et al.; Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine.; N Engl J Med; 2000; Vol. 343; pp. 180-4;
  ISSN: 0028-4793;
  PUBMED: 10900277
  Rating: Basis for recommendation
  Comments:In patients with chronic renal insufficiency, acetylcysteine (600 mg twice-daily x 48 hrs) plus hydration were effective in preventing contrast-induced nephropathy compared to control (2% vs. 21%, P=0.01).