Hidonac

N-acetylcysteine.

Each vial also contains the following excipients: Sodium hydroxide, disodium edetate and water for injection.

Pharmacology: Mechanism of Action: In toxic pathology, N-acetylcysteine (NAC) exerts its effects on multiple mechanisms. The best-known effect regards its action as precursor of glutathione. N-acetylcysteine acts as precursor of cysteine needed for GSH synthesis (by deacetylation with formulation of free cysteine and by reduction of plasma cystine to cysteine with formation of oxidized NAC); increases the total amount of glutathione (GSH + GSSG), if depleted and facilitates conversion of glutathione from the oxidized form (GSSG) to the biologically active, reduced form (GSH).
Furthermore, in paracetamol poisoning, NAC acts by: Reducing the reactive metabolites (eg, NAPQI) to atoxic compounds; conjugating itself directly with the said metabolites; in a specific manner, as antioxidant agent and as precursor of sulfates necessary for the metabolism of paracetamol by sulfation.
These mechanisms justify the need of early treatment (within 10 hrs) in paracetamol poisoning, to prevent or minimize with maximum efficacy the occurrence of hepatic damage.
Likewise, important is the capacity of NAC to improve peripheral utilization of O₂, increasing delivery and peripheral extraction. In intoxications with severe hepatic insufficiency, this makes it possible to prevent or correct tissular hypoxia, which represents one of the main factors responsible for the genesis of multiple organ insufficiency. This effect is evident even in the event of delayed treatment.
Pharmacokinetics: After oral administration of 100 mg/kg, NAC is completely absorbed and undergoes rapid and extensive metabolism in the intestinal wall and liver. The elimination half-life was 5-6 hrs after IV administration. N-acetylcysteine is mainly excreted in the urine. The main urinary metabolite of NAC is the inorganic sulfate. However, during the acute paracetamol intoxication, the urinary metabolite of NAC may differ, being at least partially represented by complexation products of NAC or its derivatives with the toxin.
Teratogenicity: Evaluation of experimental animal studies does not indicate teratogenic effects.

Voluntary or accidental paracetamol poisoning.

Acetylcysteine must be administered as loading dose, early after paracetamol intake. Treatment must be continued for at least 72 hrs (see table).
In order to avoid the hypersensitivity reactions, as described under Adverse Reactions, it is advisable to use slow infusion rate. For this purpose, NAC is previously diluted with 5% Glucose or with physiological solution.


Click on icon to see table/diagram/image

Cases of overdose were characterized by similar symptomatology as those observed in the case of adverse events. In case of overdose, treatment must be suspended. Overdose treatment is based on symptomatic treatment and/or resuscitation.

Known hypersensitivity to N-acetylcysteine or to other chemically correlated substances.

The possible presence of sulfurous odor does not indicate an alteration of Hidonac but is characteristic of NAC, being the active ingredient. The administration of NAC at high doses may reduce the prothrombin time. However, it is not established whether this is due to a biological action of NAC or the result of an analytical interference. In any way, the monitoring of coagulation factors is advisable, particularly in case of liver transplantation. N-acetylcysteine may interfere with the determination of salicylates (colorimetric method) and with the determination of plasma and urinary ketones (nitroprusside test).
Anaphylactic reactions may occur when IV acetylcysteine is directly administered at high doses as well as when very fast rate is used. Treatment of those reactions must be symptomatic. Therefore, Hidonac must be administered as described in Dosage & Administration. Patients suffering from bronchial asthma or with a history of asthma must be closely controlled since bronchospasm may occur during treatment. In such event, the treatment must be immediately suspended. Intravenous administration must be done in a hospital under strict medical surveillance.
Use in pregnancy & lactation: Evaluation of experimental animal studies does not indicate teratogenic effects. The decision to use NAC at antidotal doses during pregnancy and lactation should be based on assessment of the benefit-to-risk ratio, taking into consideration the particular characteristic of each case and in particular, the risk for the mother and fetus induced by toxicant in the absence of specific treatment. In any case, lactation must be suspended in case of poisoning.

Evaluation of experimental animal studies does not indicate teratogenic effects. The decision to use NAC at antidotal doses during pregnancy and lactation should be based on assessment of the benefit-to-risk ratio, taking into consideration the particular characteristic of each case and in particular, the risk for the mother and fetus induced by toxicant in the absence of specific treatment. In any case, lactation must be suspended in case of poisoning.

After IV administration of acetylcysteine, the following anaphylactic reactions have been seldom reported: Urticaria, angioedema, bronchospasm, nausea, vomiting, hypertension, tachycardia, dizziness and fever. These are probably pseudoallergic reactions due to histamine release. These symptoms may require an urgent therapy.

Interaction between acetylcysteine and antibiotics were reported. However, these are not remarkable when NAC is administered as treatment for paracetamol poisoning.
Incompatibilities: Mixing Hidonac with other drugs is not advisable. Since NAC can react chemically with rubber, iron, copper, etc, it is advisable to use glass or plastic materials.

Shelf-Life: 3 years in the original packaging and when properly stored; 24 hrs, at temperature (25±2°C), as solution for phleboclysis.

Antidotes & Detoxifying Agents

V03AB23 - acetylcysteine ; Belongs to the class of antidotes. Used to neutralize paracetamol overdose.

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