MUCINAC 600 Tablets (Acetylcysteine)

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1 Published on: 10 Jul 2014 MUCINAC 600 Tablets (Acetylcysteine) Composition MUCINAC 600 Tablets Each effervescent tablet contains: Acetylcysteine 600 mg Dosage Form Oral Tablet Pharmacology Pharmacodynamics N-Acetylcysteine (NAC) is the N-acetyl derivative of the natural amino acid, L-cysteine. : The viscosity of pulmonary mucus secretions depends on the concentrations of mucoprotein. The latter increases with increasing purulence owing to the presence of cellular debris. The mucolytic action of acetylcysteine is related to the sulphhydryl group in the molecule. This group opens disulphide linkages in the mucus, thereby lowering the viscosity. As an Antioxidant: Increasing evidence shows that oxidative stress plays a major role in the development of various human diseases. The imbalance between oxidants and antioxidants is caused by an increased number of oxidants and/or deficiencies in the antioxidant system. All tissues are vulnerable to lesions caused by toxic agents, but due to its location, anatomy and function, the surface epithelium of the lungs is among the most vulnerable. Oxidative stress has been implicated in the pathogenesis of a variety of pulmonary diseases. Reactive oxygen species (ROS) are normally present in the lungs and are essential for life. Simultaneously, there is an extensive network of intra- and extracellular antioxidants. An increased number of ROS and/or (relative) reductions in the antioxidative defence mechanisms may lead to a variety of pathological alterations. Maintaining adequate intracellular levels of glutathione is essential for overcoming the harmful effects of toxic agents. Reduced levels of total glutathione, one of the most important antioxidants in the lungs, in the epithelial lining fluid (ELF) have been found in acute respiratory distress syndrome (ARDS), asymptomatic HIV infection, and interstitial lung diseases like idiopathic pulmonary fibrosis (IPF), cystic fibrosis, and recipients of lung transplants. The availability of amino acids for glutathione synthesis is a fundamental factor in its regulation. Cellular amounts of glutamic acid and glycine, but not cysteine, are plentiful. Consequently, glutathione synthesis depends on the availability of cysteine. Glutathione levels may be increased by introducing additional cysteine. NAC exerts an indirect antioxidant effect related to its role as a glutathione precursor. NAC protects the respiratory epithelium against the aggressive activity of toxic agents by acting as a precursor of glutathione, thereby avoiding

2 pulmonary tissue lesions. NAC has been shown to reduce the extent of liver injury following acetaminophen overdose. Its effectiveness depends on early oral administration, with benefits seen principally in patients treated within 16 hours of the overdose. NAC probably protects the liver by maintaining or restoring the glutathione levels, or by acting as an alternate substrate for conjugation with, and, therefore, detoxification of the reactive metabolite. There is some evidence that reactive oxygen species have a role in the renal damage caused by contrast agents. NAC is thought to act either as a free-radical scavenger or a reactive sulphhydryl compound that increases the reducing capacity of the cell. It may also increase the biologic effects of nitric oxide (NO) by combining with NO to form S- nitrosothiol, which is a more stable form and a potent vasodilator. This interaction may limit the production of the damaging peroxinitrite radical because NAC would compete with the superoxide radical for NO. It also increases the expression of NO synthase and may, therefore, also improve blood flow. Pharmacokinetics NAC is rapidly absorbed following an oral dose; however, extensive first-pass metabolism by the cells of the small intestine and the liver results in the incorporation of NAC into protein peptide chains and the formation of a variety of metabolites of NAC. Only a small percentage of the intact NAC molecule arrives in the plasma, and subsequently in tissues. Only 3% of radioactively-labelled NAC is excreted in the faeces following oral administration, indicating an almost complete absorption of NAC and its metabolites. Peak concentrations of NAC typically appear in the plasma in less than 1 hour following oral administration. The plasma half-life of free NAC is estimated to be about 2.15 hours, and virtually no NAC is detectable hours post-administration. Between 13 38% of a radioactive oral dose is recovered in the urine within 24 hours. Researchers have estimated the oral bioavailability of the intact NAC molecule to be between 4 10%. Indications MUCINAC 600 Tablets are indicated as adjuvant therapy for patients with abnormal, viscid, or inspissated mucus secretions in such conditions as: Chronic bronchopulmonary disease (chronic emphysema, emphysema with bronchitis, chronic asthmatic bronchitis, tuberculosis, bronchiectasis, and primary amyloidosis of the lungs) Acute bronchopulmonary disease (pneumonia, bronchitis, tracheobronchitis) Pulmonary complications of cystic fibrosis Tracheostomy care Pulmonary complications associated with surgery Use during anaesthesia Post-traumatic chest conditions Atelectasis due to mucus obstruction Diagnostic bronchial studies (bronchograms, bronchospirometry, and bronchial- wedge catheterization) Acetylcysteine, administered orally, is indicated as an antidote to prevent or lessen hepatic injury that may occur following the ingestion of a potentially hepatotoxic quantity of acetaminophen. It is essential to initiate treatment as soon as possible after the overdose and, in any case, within 24 hours of ingestion.

3 Dosage And Administration One 600 mg oral MUCINAC 600 Tablets daily is recommended for adults and adolescents, aged 14 years and older. NAC as a loading dose of 140 mg/kg orally, followed by 70 mg/kg orally for every 4 hours for 17 additional doses is the standard protocol. Contraindications Acetylcysteine is contraindicated in those patients who are sensitive to it. There are no contraindications to oral administration of acetylcysteine in the treatment of acetaminophen overdose. Warnings And Precautions After proper administration of acetylcysteine, an increased volume of liquefied bronchial secretions may occur. When cough is inadequate, the airway must be maintained open by mechanical suction, if necessary. Where there is a mechanical block due to a foreign body or local accumulation, the airway should be cleared by endotracheal aspiration, with or without bronchoscopy. Asthmatics under treatment with acetylcysteine should be watched carefully. Most patients with bronchospasm are quickly relieved by the use of a bronchodilator. If bronchospasm progresses, the medication should be discontinued immediately. Generalized urticaria has been observed rarely in patients receiving oral acetylcysteine for acetaminophen overdose. If this occurs or other allergic symptoms appear, treatment with acetylcysteine should be discontinued, unless it is deemed essential, and the allergic symptoms can be otherwise controlled. If encephalopathy due to hepatic failure becomes evident, acetylcysteine treatment should be discontinued to avoid further administration of nitrogenous substances. There are no data indicating that acetylcysteine influences hepatic failure, but this remains a theoretical possibility. Occasionally, severe and persistent vomiting occurs as a symptom of acute acetaminophen overdose. Treatment with oral acetylcysteine may aggravate the vomiting. Patients at risk of gastric haemorrhage (e.g., oesophageal varices, peptic ulcers, etc.) should be evaluated concerning the risk of upper gastrointestinal haemorrhage versus the risk of developing hepatic toxicity, and treatment with acetylcysteine given accordingly. Drug Interactions Drug stability and safety of MUCINAC 600 Tablets (acetylcysteine), when mixed with other drugs, have not been established. Pregnancy

4 Pregnancy Category B: There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies may not always be predictive of human responses, this drug should be used during pregnancy only if clearly needed. Lactation It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when acetylcysteine is administered to a nursing mother. Geriatric Use Patients suffering from bronchial asthma must be strictly controlled during the therapy. Should bronchospasm occur, the treatment must immediately be suspended. The possible presence of a sulphurous odour does not indicate any alteration in the product, but is a characteristic of the active ingredient contained in this preparation. Undesirable Effects Generally, NAC is well tolerated. However, mild effects such as nausea and vomiting may be observed. Adverse reactions include tinnitus, headache, chills and hemoptysis. Rarely, hypersensitivity reactions like urticaria or bronchospasm may be seen. Adverse effects have included stomatitis, nausea, vomiting, fever, rhinorrhoea, drowsiness, clamminess, chest tightness, and bronchoconstriction. Clinically overt acetylcysteine-induced bronchospasm occurs infrequently and unpredictably, even in patients with asthmatic bronchitis or bronchitis complicating bronchial asthma. Acquired sensitization to acetylcysteine has been reported rarely. Reports of sensitization in patients have not been confirmed by patch testing. Sensitization has been confirmed in several inhalation therapists who reported a history of dermal eruptions after frequent and extended exposure to acetylcysteine. Reports of irritation to the tracheal and bronchial tracts have been received and although haemoptysis has occurred in patients receiving acetylcysteine, such findings are not uncommon in patients with bronchopulmonary disease and a causal relationship has not been established. As An Antidote for Acetaminophen Overdose Oral administration of NAC, especially in the large doses needed to treat acetaminophen overdose, may result in nausea, vomiting and other gastrointestinal symptoms. Rash, with or without mild fever, has been observed rarely. Overdosage No particular symptoms have been observed in patients accidentally taking high doses of NAC. However, in cases of overdosage, treatment should be symptomatic and supportive. Packaging Information MUCINAC 600 TABLETS... Strip of 10 effervescent tablets Last updated: August 2015 Last reviewed: August 2015

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