The Cathay Drug Co., Inc.
Each mL of solution contains acetylcysteine 100 mg.
PHARMACOLOGICAL AND PHARMACOKINETIC PROPERTIES
N-acetylcysteine (NAC), active ingredient of FLUIMUCIL, exerts an intensive mucolytic-fluidifying action on mucous and mucopurulent secretions by depolymerizing the mucoproteic complexes and the nucleic acids which confer viscosity to the vitreous and purulent component of the sputum and other secretions. It is a well-established mucolytic with a proven efficacy in the treatment of acute and chronic bronchitis.
Furthermore, NAC exerts a direct antioxidant action, having a free thiol (-SH) nucleophilic group which is able to interact directly with the electrophilic group of the oxidant radicals. Of particular interest is the recent finding that acetylcysteine protects α1-antitrypsin enzyme inhibiting elastase from the inactivation by hypochlorous acid (HOCl), a powerful oxidant agent produced by the myeloperoxidase enzyme of activated phagocytes.
In addition, due to its molecular structure, acetylcysteine can easily cross the cellular membranes. Inside the cell, acetylcysteine is deacetylated to L-cysteine, an amino acid indispensable for the glutathione synthesis (GSH).
GSH is a highly reactive tripeptide found ubiquitously in the various tissues of animal and is essential for the maintenance of functional capacity as well as cellular morphological integrity. It represents the most important protective endocellular mechanism against oxidant radicals, either of external or internal nature, as well as toward numerous cytotoxic substances.
These activities enable ACETYLCYSTEINE (FLUIMUCIL) particularly suitable for the treatment of acute and chronic affections of the respiratory system, characterized by thick, viscous mucous and mucopurulent secretions.
Acetylcysteine plays a role of primary importance in the maintenance of adequate GSH levels contributing to the cellular protection from harmful agents which, through progressive GSH depletion, would be able to express their cytotoxic action as in the case of paractemol poisoning.
Due to this mechanism of action, acetylcysteine is also indicated as a specific antidote in paracetamol poisoning and during treatment with cyclophosphamaide-induced hemorrhagic cystitis, in the latter case, it provides the –SH groups necessary to inactivate acrolein, the cyclophosphamide metabolite in which uropathy during treatment is ascribed.
Due to its antioxidant property and as a precursor of endocellular glutathione, acetylcysteine also exerts a protective action on the respiratory airways by withstanding damage caused by the oxidizing agents.
Acetylcysteine is quickly absorbed after oral administration. Plasma concentrations reached its peak after 2-3 hours and lasted high for 24 hours.
Lung tissue concentrations of unchanged drug assayed 5 hours after administration demonstrate the presence of high concentrations of acetylcysteine.
Acetylcysteine (FLUIMUCIL) is indicated in the treatment of respiratory conditions characterized by thick and viscous hypersecretions due to acute bronchitis, chronic bronchitis and its exacerbation, pulmonary emphysema, mucoviscidosis and bronchiectasis.
Otorhinolaryngology: catarrhal otitis, tubal catarrh; mucocrustal and mucopurulent rhinitis, sinusitis, rhinopharyngitis, pharyngo-laryngitis, laryngo-tracheitis; prophylaxis and treatment of obstructive and infectious complications of tracheotomy; preparation to bronchoscopy, bronchography, bronchoaspiration, etc.
Medicine-Pediatrics: acute and chronic bronchitis; asthmatic bronchitis, emphysema, chronic bronchopneumonia and pneumonia, pulmonary abscess, bronchiectasis, pulmonary atelectasis, bronchiolitis, mucoviscidosis, certain forms of neonatal asphyxia, etc.
Surgery: prophylaxis and treatment of bronchopulmonary complications following surgical interventions (on thorax, abdomen, etc)
Pulmonary Tuberculosis: bronchial catarrh associated with pulmonary tuberculosis, retention of secretion due to insufficient drainage of cavity lesions.
In all cases of above mentioned bronchopulmonary conditions, when topical treatment is difficult or impossible, or when the physician considers the systemic route to be preferable (lack of cooperation on the part of the patient, bedridden patients, respiration in closed circuit, etc.)
DOSAGE AND ADMINNISTRATION
Nebulize 1 ampule each time, 1 to 2 times daily for 5 to 10 days or more. Due to good drug safety profile, the frequency of administration and relative dose may be modified by the physician within acceptable limits, according to the clinical response and the therapeutic effect, without the need to differentiate the dose of adults from those in children.
Administration of Acetylcysteine (FLUIMUCIL) ampules is by deep intramuscular injection.
The recommended dosage is 1 ampule 1 to 2 times daily. Dose should be halved in small children.
When administered through the intramuscular route, a slight and transient burning sensation at the site of injection has been reported.
Do not use previously opened ampules for injection.
Intravenous Injection (not as an antidote)
The product must be given by slow infusion in saline solution or 5% glucose solution.
Adults: 1 ampule once or twice daily
Children: half an ampule once or twice daily.
The duration of treatments should be established on the basis of the clinical evaluation. The high general and local tolerability of the product allows for long term treatment.
Known hypersensitivity to the acetylcysteine.
WARNINGS AND PRECAUTIONS
Administration of acetylcysteine by aerosol inhalation in particular, can at the beginning of treatment liquefy the bronchial secretions and simultaneously increase the volume. If the patient is unable to expectorate properly, it is necessary to clear the airways by postural drainage or by bronchosuction to avoid retention of secretions.
Patients suffering from bronchial asthma must be closely monitored as bronchospasm may occur during treatment. In such event, the treatment must be suspended immediately. It should be used with caution in asthmatic patients and patients with a history of peptic ulceration.
Acetylcysteine (FLUIMUCIL) ampule contains 43 mg (1.9 mmol) sodium per dose. To be taken into consideration by patients on a controlled sodium diet.
The possible presence of a sulfur-like odor upon opening the ampule or upon transfer to the aerosol equipment, may exceptionally assume a pink color. This however, does not affect the efficacy and safety of the product.
Since acetylcysteine can react chemically with certain materials (e.g. rubber, iron, copper), the aerosol apparatus used should be made of glass and plastic material. Wash the apparatus after use.
The ampule containing Acetylcysteine (FLUIMUCIL) should be used immediately upon opening. Opened ampule must be refrigerated and used within 24 hours. Do not use for injection any previously opened ampule.
If acetylcysteine is mixed with bronchodilators or other drugs, it must be used immediately and discard any remaining portion.
Pregnancy and lactation
Animal studies indicated no evidence of teratogenic effect of Acetylcysteine. However, as for the majority of pharmaceutical preparations, its administration during pregnancy and lactation should be performed only when strictly necessary and under direct physician’s control.
Interaction studies have been performed only in adults. Antitussive drugs and acetylcysteine should not be concurrently administered because the reduction in cough reflex could lead to accumulation of bronchial secretions.
Concurrent administration of nitroglycerin and acetylcysteine has been shown to cause significant hypotension and enhance temporal artery dilation. If concurrent nitroglycerin and acetylcysteine therapy is necessary, patients should be monitored for hypotension, which can be severe, and warned of the possibility of headaches.
Reports of inactivation of antibiotics resulting from acetylcysteine so far only relate to in vitro tests in which the relevant substances were mixed directly. Therefore, dissolution of acetylcysteine formulations concomitantly with other drugs is not recommended.
Acetylcysteine may interfere with colorimetric assay method for salicylate measurement.
Acetylcysteine may interfere with urine ketone test.
The following adverse reactions were reported during post-marketing experience; their frequency is not known (cannot be estimated from the available data).
|System Organ Class||Adverse Reactions|
|Immune System disorders||Hypersensitivity|
|Respiratory, thoracic and mediastinal disorders||Bronchospasm, rhinorrhea|
|Gastrointestinal disorders||Stomatitis, vomiting, nausea|
|Skin and subcutaneous tissue disorders||Urticarial, rash, pruritus|
|System Organ Class||Adverse Reactions|
|Immune System Disorders
|Anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, hypersensitivity|
|Respiratory, thoracic and Mediastinal Disorders||Bronchospasm, dyspnea
|Gastrointestinal Disorders||Vomiting, nausea|
|Skin and subcutaneous tissue Disorders||Angioedema, urticaria, flushing, rash, pruritus|
|General disorders and administration site conditions||Face edema
|Investigations||Blood pressure decreased, prothrombin time prolonged|
In very rare cases, the occurrence of severe skin reactions such as Stevens-Johnson syndrome and Lyell’s syndrome has been reported in temporal connection with the administration of acetylcysteine.
In most cases, at least one co-suspect drug more probably involved in triggering the reported mucocutaneous syndrome could be identified. Medical advice should be sought immediately if any new changes to the skin or mucous membranes occur, and acetylcysteine should be stopped immediately.
A decrease in platelet aggregation in the presence of acetylcysteine has been confirmed by various investigations. The clinical significance has not been established.
By intravenous route
Symptoms of overdosage are similar, but more severe than that observed in the case of adverse events.
Treatment of overdose is based on immediate discontinuation of the infusion administration and symptomatic treatment and resuscitation. There are no specific antidotal treatments. Acetylcysteine is dialyzable.
By topical route
No cases of overdose by topical route have been reported. Theoretically, when acetylcysteine is administered in large doses locally, a high degree of liquefaction of mucopurulent secretions may occur, especially in those patients with inadequate coughing reflex or expectoration. In cases such as this and for any reported overdose, it may be necessary to use mechanical methods of bronchial suction.
EFFECTS ON THE ABILITY TO DRIVE AND USE MACHINES
No evidence exists that the drug can modify attention or reaction time.
Store at temperatures not exceeding 30°C.
FORMULATION AND AVAILABILITY
Acetylcysteine (FLUIMUCIL) Solution for Inhalation, 300 mg/3 mL ampule, is supplied in box of 5 ampules.
Acetylcysteine (FLUIMUCIL) Solution for Injection, 300 mg/3 mL ampule, is supplied in box of 5 ampules.
KEEP OUT OF REACH OF CHILDREN.
DO NOT USE BEYOND EXPIRY DATE.