100 mg:

ACC100 mg powder for oral solution:

Secretolytic therapy in acute and chronic bronchopulmonary diseases accompanied by impaired formation and transport of mucus in adults, adolescents and children from 2 years of age.

 

200 mg:

ACC 200     mg     powder     for     oral     solution:   Secretolytic therapy in acute and chronic  bronchopulmonary diseases accompanied by impaired formation and transport of mucus in adults, adolescents and children from 6 years of age.

 

600 mg:

ACC 600     mg     powder     for     oral     solution:   Secretolytic therapy in acute and chronic  bronchopulmonary diseases accompanied by impaired formation and transport of mucus in adults and adolescents from 14 years of age.

Posology

 

The following dose is recommended for ACC100 mg powder for oral solution:

 

Adults and adolescents from 14 years of age

2 sachets 2-3 times daily (equivalent to 400-600 mg acetylcysteine per day)

 

Children and adolescents from 6-14 years of age

1 sachet 3-4 times daily (equivalent to 300-400 mg acetylcysteine per day)

 

Children from 2-5 years of age

1 sachet 2-3 times daily (equivalent to 200-300 mg acetylcysteine per day)

 

 

The following dose is recommended for ACC200 mg powder for oral solution:

 

 

Adults and adolescents from 14 years of age

1 sachet 2-3 times daily (equivalent to 400-600 mg acetylcysteine/day)

 

 

 

The following dose is recommended for ACC600 mg powder for oral solution:

 

Adults and adolescents from 14 years of age take 1 sachet once daily (equivalent to 600 mg acetylcysteine per day).

 

Method of administration

 

ACC100 mg and 200 mg powder for oral solution is to be taken dissolved in a glass of water after meals.

 

 

 

 

Duration of use

Nationally completed name should not be taken for more than 4-5 days without medical advice.

 

Note:

The possible presence of sulfurous smell is not indicative of product alterations but is a characteristic of the active ingredient contained in this preparation.

 hypersensitivity to acetylcysteine or to any of the excipients listed in section 6.1 On account of the high content of active substance, ACC100 mg powder for oral solution must not be used in children of less than 2 years of age. Other appropriate pharmaceutical forms are available. On account of the high content of active substance, ACC200 mg powder for oral solution must not be used in children of less than 6 years of age. Other appropriate pharmaceutical forms are available. On account of the high content of active substance, ACC600 mg powder for oral solution must not be used in children and adolescents of less than 14 years of age. Other appropriate pharmaceutical forms are available.

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. If cutaneous and mucosal changes newly occur, medical advice should be sought without delay and use of acetylcysteine be terminated.

 

Cave during use in patients with bronchial asthma and in patients with anamnestic ulcers.

 

The use of acetylcysteine, especially in early treatment can lead to liquefaction and thus to an increase in volume of bronchial secretions. If the patient is unable to cough up enough of this, appropriate measures (such as postural drainage and aspiration) should be performed.

 

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).

 

100 mg:

ACCcontains sucrose, lactose and glucose

This medicinal product contains 2.8 g sucrose in each sachet. This should be taken into account in patients with diabetes mellitus.

Patients with rare hereditary problems of fructose and galactose intolerance, total lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.

 

200 mg:

ACC      contains      sucrose,     lactose     and      glucose    This medicinal product contains    2.7 g sucrose in each sachet. This should be taken into account in patients with diabetes mellitus. Patients with rare hereditary problems of fructose and galactose intolerance, total lactase deficiency, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product.

 

600 mg:

 

ACC         contains         sucrose         and         sodium This medicinal product contains 2.0 g sucrose in each sachet. Patients with rare hereditary problems of fructose intolerance, glucose- galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product. This medicinal product contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially

`sodium free´.

Interaction studies have only been performed in adults.

 

Combination with antitussives

Combined use 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.

 

Antibiotics

Reports to date 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.

 

Activated carbon in high doses

The use of activated charcoal may reduce the effect of acetylcysteine.

 

Acetylcysteine/ glyceryl trinitrate

Co-administration of acetylcysteine can result in an enhancement of vasodilator and antiplatelet effects of glyceryl trinitrate (nitroglycerin).

If a common treatment with nitroglycerin and acetylcysteine is considered necessary, the patient should be monitored for a potential hypotension, which could be serious and may indicated by headache.

 

Changes in the determination of laboratory parameters

•  Acetylcysteine may affect the colorimetric assay of salicylates.

•  In urine tests, acetylcysteine may influence the results of the determination of ketone bodies.

 

The dissolution of acetylcysteine formulations together with other medicinal products is not recommended.

Fertility

Data concerning effects of acetylcysteine on human fertility are not available. In animal studies, no harmful effects on fertility were observed for therapy-relevant doses of acetylcysteine (see section 5.3).

 

 

Pregnancy

There are no adequate clinical data from the use of acetylcysteine in pregnant women. Animal studies

 

do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Whenever possible, use during pregnancy should be avoided and only take place after a strict benefit-risk assessment.

 

Breast-feeding

No information is available regarding excretion of acetylcysteine or its metabolites into breast milk. A risk for the breast-fed child cannot be excluded. Use during lactation should only take place after a strict benefit-risk assessment.

Acetylcysteine has no influence on the ability to drive and use machines.

The evaluation of adverse reactions is based on the following information on frequencies: Very common (³ 1/10)

Common (³ 1/100 to < 1/10) Uncommon (³ 1/1,000 to < 1/100) Rare (³ 1/10,000 to < 1/1,000) Very rare (< 1/10,000)

Not known (cannot be estimated from the available data)

 

 

Tabulated list of adverse reactions:

 

System organ class	Undesirable effects
	Uncommon	Rare	Very rare	Not known
Immune system disorders	Hypersensitivity reactions		Anaphylactic shock, anaphylactic/anaphylactoi d reactions

 

Nervous system disorders	Headache
Ear and labyrinth disorders	Tinnitus
Cardiac disorders	Tachycardia
Vascular disorders			Haemorrhage
Respiratory, thoracic and mediastinal disorders		Bronchospasm, dyspnoea
Gastrointestinal disorders	Vomiting, diarrhoea, stomatitis, abdominal pain, nausea	Dyspepsia
Skin and subcutaneous tissue disorders	Urticaria, rash, angioedema, pruritus, exanthema
General disorders and administration site conditions	Fever			Facial oedema
Investigations	Hypotension

 

 

In very rare cases, severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported in temporal association with the use of acetylcysteine. In most of these reported cases, at least one additional medicinal product Tthat could potentially have intensified the described mucocutaneous effects was being taken at the same time.

 

In case of recurrence skin and mucosal lesions, medical advice should be sought at once and the use of acetylcysteine terminated immediately.

 

A decreased blood platelet aggregation in the presence of acetylcysteine has been confirmed by various studies. The clinical relevance has not yet been clarified to date.

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 were tolerated without any symptoms of intoxication.

 

a)      Symptoms of intoxication

Overdoses may lead to gastrointestinal symptoms such as nausea, vomiting and diarrhoea. Infants are at risk of hypersecretion.

 

b)      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.

Pharmacotherapeutic group: Cough and cold preparations; Mucolytics ATC Code: R05C B01

 

Acetylcysteine is a derivative of the amino acid cysteine. The efficacy of acetylcysteine is secretolytic and secretomotoric in the area of the respiratory 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 them 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.

Absorption

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.

 

Distribution

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%.

 

Biotransformation

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.

 

Elimination

Pharmacokinetic studies with intravenous administration of acetylcysteine revealed a distribution volume of 0.47 l/kg (in total) or 0.59 l/kg (reduced); the plasma clearance was determined to be 0.11 l/h/kg (in total) and 0.84 l/h/kg (reduced), respectively. The elimination half-life after intravenous administration is 30-40 minutes while excretion follows three-phase kinetics (alpha, beta, and terminal gamma phase).

 

Acetylcysteine crosses the placenta and is detected in cord blood. No information is available regarding excretion into breast milk.

 

No knowledge is available concerning the behaviour of acetylcysteine at the blood-brain barrier in humans.

 

a)      Acute toxicity

The acute toxicity in animal experiments is low. For the treatment of overdoses, see section 4.9.

 

b)      Chronic toxicity

Studies in various animal species (rat, dog) with a duration of up to one year did not show any pathological alterations.

 

c)       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.

d)      Reproductive toxicology

No malformations were detected in embryotoxicity studies in rabbits and rats. Studies of fertility and perinatal or postnatal toxicity were negative.

 

Acetylcysteine passes the placenta in rats and was detected in amniotic fluid. The concentration of the metabolite L-cysteine is above the maternal plasma concentration in placenta and foetus for up to 8 hours after oral administration.

ACC 100 mg and 200 mg powder for oral solution: Sucrose Ascorbic acid (E 300)

Saccharin

Orange flavour (contains lactose and glucose)

 

ACC600 mg powder for oral solution: Sucrose Ascorbic acid (E 300)

Saccharin sodium Lemon flavour Honey flavour

The dissolution of acetylcysteine formulations together with other medicinal products is not recommended.

 

24 Months The reconstituted solution should be used immediately after dissolving.

ACC100 mg and 200 mg powder for oral solution: Do not store above 30°C.

ACC name 600 mg powder for oral solution: This medicinal
product does not require any special storage conditions.
For storage conditions after reconstitution of the medicinal product, see section 6.3.

The powder for oral solution is packed in polyethylene-aluminium-paper sachets and inserted in a carton. Sachets containing 3 g of powder.

Pack                     sizes: 20 sachets

 

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.