Hidonac

Introduction

Acetylcysteine, originally approved by the FDA in 1963, is used for treating acetaminophen toxicity and preventing hepatotoxicity. It is also researched for its antioxidant effects, potentially reducing damage in various organs, including the heart, kidney, liver, and lungs.

Mechanism of Action

Acetylcysteine acts as an antioxidant, scavenging oxygen free radicals and stabilizing cellular signals. It enhances nitric oxide (NO) effects by forming S-nitrosothiol, a potent vasodilator, preventing oxidative tissue damage. In the case of acetaminophen overdose, acetylcysteine provides sulfhydryl groups to detoxify the toxic acetaminophen metabolite, restoring depleted glutathione and preventing hepatotoxicity.

Pharmacokinetics

Intravenous Route: The volume of distribution (Vdss) is 0.47 L/kg, with protein binding of 83%. Acetylcysteine undergoes first-pass metabolism into cysteine and disulfides (NN-diacetylcysteine and N-acetylcysteine). Cysteine is further metabolized into glutathione. The half-life for reduced acetylcysteine is 2 hours, while total acetylcysteine has a half-life of 5.6 hours in adults and 11 hours in newborns. The drug is excreted primarily in the urine (13% to 38%).

Indications

Acetylcysteine is used for the prevention of hepatotoxicity following acetaminophen overdose or repeated supratherapeutic ingestion. It is also researched for use as an antioxidant in reducing ischemic damage in vital organs.

Dosing

Intravenous dosage (21-hour regimen): Adults, adolescents, and children weighing more than 40 kg: Administer a total dose of 300 mg/kg over 21 hours, divided into three continuous infusions. The first dose is 150 mg/kg (maximum 15,000 mg) in 200 mL, infused over 1 hour. The second dose is 50 mg/kg in 500 mL, infused over 4 hours, and the final dose is 100 mg/kg in 1000 mL, infused over 16 hours.

Administration

Administer acetylcysteine intravenously as a continuous infusion. Ensure proper dilution of the solution based on the patient’s weight. The infusion should be closely monitored to prevent adverse reactions.

Storage/Stability

Store intact vials at 20°C to 25°C (68°F to 77°F). Following reconstitution, the solution remains stable for 24 hours at room temperature. Any color change (light pink or purple) does not affect the safety or efficacy of the solution.

Adverse Reactions

• Autoimmune disease (14-18%)
• Anaphylactoid reactions (1-18%)
• Flushing (1-3%)
• Tachycardia (1-4%)
• Edema (1-2%)
• Urticaria (≤21%)
• Vomiting (2-10%)
• Nausea (1-6%)
• Rash (2-21%)
• Pharyngitis (≤1%)
• Throat tightness (≤1%)

Monitoring Parameters

For acetaminophen overdose, monitor for the development of anaphylaxis or anaphylactoid reactions. Regularly assess liver function tests (LFTs), serum creatinine, bilirubin, blood glucose, and INR. Follow the Rumack-Matthew nomogram to predict hepatotoxicity based on serum acetaminophen concentrations.

Use in Specific Populations

Pregnancy: Acetylcysteine crosses the placenta in animal studies. No teratogenic effects were observed in rats, but maternal and fetal toxicity were seen in rabbits. Despite this, it is considered compatible with pregnancy. Administer cautiously based on patient conditions.
Breast-feeding: Acetylcysteine is present in breast milk in small quantities. Monitor breastfeeding infants for gastrointestinal disturbances such as diarrhea or thrush.

Pharmacodynamics

Absorption: Rapidly absorbed through intravenous administration.
Distribution: Vd: 0.47 L/kg, 83% protein binding.
Metabolism: Undergoes extensive first-pass metabolism.
Excretion: Primarily via urine (13-38%).

Contraindications

No absolute contraindications; however, caution is advised in patients with asthma due to the risk of bronchospasm. Monitor patients with a history of anaphylaxis carefully.

References

Watson WA, McKinney PE. Activated charcoal and acetylcysteine absorption: issues in interpreting pharmacokinetic data. DICP 1991; 25(10):1081-1084.
Mucomyst (N-acetylcysteine) package insert. Princeton, NJ: Apothecon; 1998.
Acetadote (N-acetylcysteine) injection package insert. Nashville, TN: Cumberland Pharmaceuticals; 2019.
Renzi FP, Donovan JW, Morgan L, et al. Concomitant use of activated charcoal and N-acetylcysteine. Ann Emerg Med 1984;13:400.
Smilkstein MJ, Knapp GL, Kulig KW, et al. Efficacy of N-acetylcysteine in the treatment of acetaminophen overdose. N Engl J Med 1988;319(24):1557-62.
Tepel M, Van Der Giet M, Schwarzfeld C, et al. Prevention of radiographic-contrast-induced reductions in renal function by acetylcysteine. N Engl J Med 2000; 343:180-184.
Bateman DN, Dear JW, Thanacoody HK, et al. Reduction of adverse effects from intravenous acetylcysteine treatment for paracetamol poisoning: a randomized controlled trial. Lancet. 2014;383(9918):697-704.
Subramaniam RM, Suarez-Cuervo C, Wilson RF, et al. Effectiveness of prevention strategies for contrast-induced nephropathy: a systematic review and meta-analysis. Ann Intern Med. 2016;164(6):406-416.