Exflem 200

Exflem 200

acetylcysteine

Manufacturer:

Sandoz

Distributor:

UNILAB, Inc
Full Prescribing Info
Contents
Acetylcysteine.
Description
Each sachet contains Acetylcysteine 200 mg.
Action
Pharmacologic Classification: Mucolytic.
Pharmacology: Pharmacodynamics: Pharmacodynamic properties: Acetylcysteine is a derivative of the amino acid cysteine. The efficacy of acetylcysteine is secretolytic and secretomotoric in the area of the bronchial tract. It is discussed that it splits off the interconnecting disulphide bonds between the mycopolysaccharide chains and that it has a depolymerizing effect on DNA-chains (in purulent mucus). Due to these mechanisms, the viscosity of mucus should be reduced.
An alternative mechanism of acetylcysteine is meant to be based on the capacity of its reactive SH group to bind chemical radicals and to detoxify then in this way.
Furthermore, acetylcysteine contributes to an increase in glutathione synthesis, which is important for the detoxification of noxae. This provides the explanation for its antidotal effect in paracetamol intoxication.
A protective effect on the frequency and severity of bacterial exacerbations - when acetylcysteine is administered prophylactically - is described in patients with chronic bronchitis/mucoviscidosis.
Pharmacokinetics: Following oral administration, acetylcysteine is rapidly and almost completely absorbed and metabolized in the liver to cysteine, the pharmacologically active metabolite, as well as to diacetylcystine, cystine and further mixed disulphides. Due to the high first-pass effect, the bioavailability of orally administered acetylcysteine is very low (approx. 10%). In humans, maximum plasma concentrations are achieved after 1-3 hours with the maximum plasma concentration of the metabolite cysteine in the range of approx. 2 μmol/l. The protein binding of acetylcysteine was determined to be about 50%.
Acetylcysteine and its metabolites occur in three different forms in the organism: partially in free form, partially bound to proteins via labile disulphide bonds and partially as incorporated amino acid. Acetylcysteine is excreted almost exclusively in the form of inactive metabolites (inorganic sulphates, diacetylcystine) via the kidneys. The plasma half-life of acetylcysteine is approximately 1 hour and is mainly determined by the rapid hepatic biotransformation. Impaired hepatic function therefore leads to prolonged plasma half-lives of up to 8 hours.
Pharmacokinetic studies with intravenous administration of acetylcysteine revealed a distribution volume of 0.47 L/kg BW (in total) or 0.59 L/kg BW (reduced); the plasma clearance was determined to be 0.11 L/h/kg BW (in total) and 0.84 L/h/kg BW (reduced), respectively. The elimination half-life after i.v. administration is 30-40 minutes while excretion follows three-phase kinetics (α, β, and terminal δ phase).
Acetylcysteine crosses the placenta and is detectable in cord blood. No information is available regarding the excretion into breast milk.
No information is available concerning the behaviour of acetylcysteine at the blood-brain barrier in humans.
Toxicology: Preclinical safety data: Acute toxicity: See Overdosage.
Chronic toxicity: Studies in various animal species (rat, dog) with a duration of up to one year did not show any pathological alterations.
Tumorigenic and mutagenic potential: No mutagenic effects of acetylcysteine are to be expected. An in vitro test was negative.
No studies of a tumorigenic potential of acetylcysteine have been carried out.
Reproductive toxicology: Embryotoxicity studies have been performed in pregnant rabbits and rats receiving oral doses of acetylcysteine during organogenesis. The dose was 250, 500 and 750 mg/kg in rabbits and 500-1,000 mg/kg in rats. No malformations were observed in any of the studies.
Fertility studies, perinatal and postnatal studies have been performed with oral acetylcysteine in rats. The results of these studies showed that acetylcysteine does not affect gonadal function, fertility rape, parturition, lactation or the development of newborn animals.
N-acetylcysteine passes the placenta in rats and was identified in amniotic fluid. The concentration of the metabolite L-cysteine in placenta and foetus is above the maternal plasma concentration for up to 8 hours after oral administration.
Indications/Uses
Secretolytic therapy in cases of acute and chronic bronchopulmonary diseases accompanied by impaired formation and transport of mucus.
Dosage/Direction for Use
If not otherwise prescribed, the following dosage is recommended for Acetylcysteine: Adults and adolescents from 14 years of age: 1 powder sachet 2-3 times daily (equivalent to 400-600 mg acetylcysteine/day).
Children and adolescents from 6-14 years of age: 1 powder sachet twice daily (equivalent to 400 mg acetylcysteine/day).
In case of mucoviscidosis: Children and adolescents aged over 6 years 1 powder sachet 3 times daily (equivalent to 600 mg acetylcysteine/day).
Method and total duration of administration: Acetylcysteine is taken dissolved in a glass of liquid (water, tea or juice) after meals.
The duration of use depends on the type and severity of the disease and should be decided by the attending physician.
In case of chronic bronchitis and mucoviscidosis, treatment should be continued for a longer-term period in order to achieve infection prophylaxis.
Overdosage
No case of toxic overdose has been observed to date in association with oral pharmaceutical forms of acetylcysteine.
Volunteers were treated with a dose of 11.6 g acetylcysteine/day over 3 months without observing any severe adverse reactions. Oral doses up to 500 mg acetylcysteine /kg BW have been tolerated without any symptoms of intoxication.
Symptoms of intoxication: Overdoses may lead to gastrointestinal symptoms such as nausea, vomiting and diarrhoea. Infants are at risk of hypersecretion.
Therapeutic measures in case of an overdose: If necessary, according to the symptoms.
Experience gained from intravenous acetylcysteine treatment of paracetamol intoxication is available in humans with maximum daily doses of up to 30 g acetylcysteine. Intravenous administration of extremely high acetylcysteine concentrations led to partially irreversible "anaphylactoid" reactions, particularly in connection with rapid administration.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
On account of the high content of active substance, Acetylcysteine must not be used in children of less than 6 years of age.
Special Precautions
The occurrence of severe skin reactions such as Stevens-Johnson syndrome and Lyell's syndrome has very rarely been reported in association with the use of acetylcysteine. If cutaneous and mucosal alterations newly occur, medical advice should be sought without delay and the use of acetylcysteine be terminated (see also Adverse Reactions).
Cave during use in patients with bronchial asthma and patients with a history of ulcer.
Caution is advised in patients with histamine intolerance.
Longer-term therapy should be avoided in these patients, as Acetylcysteine has an effect on histamine metabolism and may lead to symptoms of intolerance (e.g. headache, vasomotor rhinitis, itching).
The use of acetylcysteine, especially at the beginning of treatment, may lead to an increased volume of liquefied bronchial secretion. If it can only be coughed off with difficulty, appropriate measures should be taken (e.g. postural drainage and removal of secretions).
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or saccharase-isomaltase deficiency should not take Acetylcysteine.
1 powder sachet contains 2.7 g sucrose (sugar), equivalent to approx. 0.23 bread units. This should be taken into account in patients with diabetes mellitus.
Acetylcysteine may be damaging to teeth (caries).
Effects on Ability to Drive and Use Machines: None known.
Use In Pregnancy & Lactation
For acetylcysteine, no sufficient clinical data on exposed pregnant women are available. Animal studies do not indicate direct or indirect harmful effects on pregnancy, embryonal/foetal development, parturition or postnatal development (see also Pharmacology: Toxicology: Preclinical safety data under Actions).
No information is available regarding excretion into breast milk.
Acetylcysteine should be used during pregnancy and lactation only after strict assessment of the benefit-risk ratio.
Adverse Reactions
The evaluation of undesirable effects is based on the following information on frequencies: Very common (≥1/10); Common (≥1/100 up to <1/10); Uncommon (≥1/1,000 up to <1/100); Rare (≥1/10,000 up to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).
General disorders and administration site conditions: Uncommon: headache, fever, allergic reactions (itching, urticaria, exanthema, rash, bronchospasm, angioedema, tachycardia and fall in blood pressure).
Very rare: anaphylactic reactions up to shock.
Not known: facial oedema.
Ear and labyrinth disorders: Uncommon: tinnitus.
Respiratory, thoracic and mediastinal disorders: Rare: dyspnoea, bronchospasm (predominantly in patients with hyperreactive bronchial system in case of bronchial asthma).
Gastrointestinal disorders: Uncommon: stomatitis, abdominal pain, nausea, vomiting, heartburn and diarrhoea.
Rare: dyspepsia.
In addition, the occurrence of haemorrhages in association with administration of acetylcysteine has very rarely been reported, partially in association with hypersensitivity reactions. A decreased blood platelet aggregation in the presence of acetylcysteine has been confirmed by different studies. The clinical relevance is not yet known.
The occurrence of severe skin reactions such as Stevens-Johnson syndrome and Lyell's syndrome has very rarely been reported in temporal connection with the use of acetylcysteine. In most of these cases, at least one another drug has been taken concomitantly which might enhance the described mucocutaneous effects.
If cutaneous and mucosal alterations newly occur, medical advice should be sought without delay and use of acetylcysteine be terminated. The use of acetylcysteine must be terminated immediately.
Various studies confirm decreased platelet aggregation during use of acetylcysteine. Its clinical significance is not yet known.
Drug Interactions
Interaction studies have only been performed in adults.
Combined administration of Acetylcysteine with antitussives (cough-relieving agents) may cause a dangerous secretory congestion due to the reduced cough reflex, so that an especially careful diagnosis is required for this combination treatment.
The use of activated charcoal may reduce the effect of acetylcysteine.
Reports on an inactivation of antibiotics (tetracyclines, aminoglycosides, penicillins) due to acetylcysteine exclusively refer to in vitro experiments in which the relevant substances were mixed directly). Nevertheless for safety reasons, oral antibiotics should be administered separately and at an interval of at least 2 hours. This does not apply to cefixime and loracarbef.
Enhanced vasolidative and anti-platelet effects of glyceryl trinitrate have been reported with concomitant administration of acetylcysteine. The clinical relevance of these finding is not yet known.
If concomitant treatment with nitroglycerin and acetylcysteine is deemed necessary, the patient should be monitored for potential hypotension which may be severe; headache may be a sign for it.
Altered determination of laboratory parameters: Acetylcysteine can affect colorimetric assays of salicylates.
In urine tests, acetylcysteine can affect the results of trials to determine ketone bodies.
It is not recommended to dissolve acetylcysteine preparations together with other medicines.
Storage
Store at temperatures not exceeding 30°C.
ATC Classification
R05CB01 - acetylcysteine ; Belongs to the class of mucolytics. Used in the treatment of wet cough.
Presentation/Packing
Powd for oral soln (sachet) 200 mg x 30's.
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