ACTION AND MECHANISM

- [MUCOLYTIC]. It is the N-acetylated derivative of the natural amino acid cysteine. It reduces the viscosity of bronchial secretions, promoting their elimination, probably due to the presence of a free thiol group. This group is capable of breaking the disulfide bonds that maintain the three-dimensional structure of mucoproteins, resulting in the fluidification of the secretion. Its effects are pH-dependent, being maximum at pH between 7 and 9.

SENIORS

No specific problems have been reported in this age group. However, liver or respiratory failure is more common in these patients, so caution is recommended when using acetylcysteine.

PATIENT ADVICE

PATIENT ADVICE:

CONTRAINDICATIONS

- Hypersensitivity to any component of the medication.

EFFECTS ON DRIVING

Acetylcysteine does not usually cause drowsiness, but some cases have been reported in rare cases. Caution is recommended when driving until it is relatively certain that the treatment does not adversely affect the patient's ability.

PREGNANCY

FDA Category B. Oral administration of 500 mg/kg/24 hours or nebulized acetylcysteine and isoproterenol for 30–35 minutes in pregnant rabbits did not reveal any teratogenicity. Peri- and postnatal studies also failed to reveal evidence of harm to the fetus or newborn. Acetylcysteine appears to cross the placenta. Adequate and well-controlled studies in humans have not been conducted, so its use is only permitted in the absence of safer therapeutic alternatives.

PHARMACOKINETICS

Oral, parenteral:
- Absorption: Following oral administration of a 200-600 mg dose, it is rapidly absorbed, reaching a Cmax of 0.35-4 mcg/ml after 0.5-1 hour. Its bioavailability is very low (4-10%), probably due to intense intestinal and first-pass hepatic metabolism.
- Distribution: It circulates in plasma both freely and bound to proteins (50%) by labile disulfide bridges or covalent peptide bonds. It diffuses extensively into extracellular fluids, primarily located in bronchial secretions. Its Vd is 0.33–0.47 l/kg.
- Metabolism: It undergoes intense intestinal and hepatic metabolism, giving rise to sulfur derivatives such as cysteine, N-acetylcystine, N,N-acetylcystine or glutathione.
- Elimination: Acetylcysteine is eliminated by metabolism (70%) and subsequent excretion in urine, either in free form (30%) or as metabolites. Its elimination half-life is 6.25 hours (oral) or 5.58 hours (intravenous).
Pharmacokinetics in special situations:
- Children: After intravenous administration, elimination half-life values of 11 hours have been found.
- Hepatic impairment: The elimination half-life is increased by 80% in patients with severe hepatic impairment or with primary or secondary biliary cirrhosis.

INDICATIONS

- [BRONCHIAL HYPERVISCOSITY].

INTERACTIONS

- Antibiotics. Acetylcysteine may be incompatible with amphotericin B, sodium ampicillin, cephalosporins, erythromycin lactobionate, or some tetracyclines. It is recommended to separate doses by at least two hours.- Antitussives. Acetylcysteine increases the fluidity of bronchial secretions, so it is not advisable to administer it together with antitussives, which could inhibit the cough reflex and lead to pulmonary obstruction.- Drugs that inhibit bronchial secretion (anticholinergics, tricyclic antidepressants, H1 antihistamines, antiparkinsonian drugs, MAOIs, neuroleptics). They may antagonize the effects of acetylcysteine.- Nitroglycerin. Acetylcysteine may enhance the vasodilatory effects of nitroglycerin and its adverse reactions at very high doses (100 mg/kg).- Metal salts. Acetylcysteine may have certain chelating effects on some metals such as gold, calcium, or iron, thereby decreasing their absorption. It is recommended to separate the intake of mineral supplements and acetylcysteine by at least two hours.

LACTATION

It is unknown whether acetylcysteine is excreted in breast milk and whether this could affect the infant. It is recommended to discontinue breastfeeding or avoid administering this medication.

CHILDREN

No specific problems have been described in this age group. Accepted use.

RULES FOR CORRECT ADMINISTRATION

Dissolve the effervescent tablets or the contents of the sachets in a glass of water, drinking once the effervescence has stopped.

POSOLOGY

- Adults, oral: 600 mg/24 h in a single dose, preferably in the morning, and with food.
- Children and adolescents under 18 years of age, oral: safety and efficacy have not been evaluated.
Missed dose: Take as soon as possible if the missed dose has been missed. Otherwise, skip the missed dose. Do not double the dose at the next missed dose.
Duration of treatment: If symptoms do not improve or worsen after 5 days of treatment, or if they are accompanied by fever, rash, headache, or persistent sore throat, consult your doctor and/or pharmacist.

PRECAUTIONS

- [LIVER FAILURE] severe, [LIVER CIRRHOSIS]. In these patients, clearance may be decreased, with a consequent increased risk of adverse reactions, so close monitoring of the patient is recommended due to the risk of anaphylactic adverse reactions.- [PEPTIC ULCER]. Acetylcysteine may occasionally cause nausea and vomiting, especially at high doses, thus increasing the risk of gastric bleeding. Furthermore, it has also been postulated that acetylcysteine ​​may increase the fluidity of gastric mucus, leading to a decrease in its protective action. Extreme caution is recommended in patients with peptic ulcer.- [ASTHMA]. In patients with asthma, severe [RESPIRATORY FAILURE] or diseases that present with [BRONCHIAL SPASM], an increase in the fluidity of secretions may lead to airway obstruction if expectoration is inadequate. Extreme caution is therefore recommended. - Increased expectoration. At the beginning of treatment, an increase in expectoration may occur due to the increased fluidity of secretions. This effect decreases after several days of treatment. If symptoms persist or worsen after five days of treatment, it is advisable to re-evaluate the clinical situation.

PRECAUTIONS RELATED TO EXCIPIENTS

- This medicine contains aspartame as an excipient, so it should be taken into account by people suffering from [PHENYLKETONURIA]. 100 mg of aspartame corresponds to 56.13 mg of phenylalanine.

ADVERSE REACTIONS

Adverse reactions to acetylcysteine are rare, mild, and transient. The most common adverse reactions are:

- Digestive. [NAUSEA], [VOMITING], [DIARRHEA] and [GASTRIC HYPERACIDITY] may occasionally occur, especially when used at high doses.

- Liver. Some cases of [elevated transaminases] have been reported following the administration of large doses of acetylcysteine, which reversed within a few days of discontinuing treatment.

- Neurological/psychological. Some cases of [HEADACHE], [DROWSINESS] have been reported.

- Respiratory. These are usually exclusive to administration by inhalation. [RHINORRHEA], [BRONCHITIS], [TRACHEITIS], [HEMOPTYSIS] and [BRONCHIAL SPASM] may occur.

- Eyepieces. [BLURRED VISION].

- Ear and labyrinth disorders: [TINNITUS].

- Allergic/dermatological. [HYPERSENSITIVITY REACTIONS] may occur 30-60 minutes after administration, presenting with generalized [URTICARIA], moderate [FEVER], [EXANTHEMATOUS ERUPTIONS], [PRURITUS], [ANGIOEDEMA], [DYSPNEA], and [HYPOTENSION]. These reactions are more frequent and severe when administered parenterally and can be fatal, whereas they are rare when administered orally or by inhalation.

In the event of allergic reactions, it is recommended to temporarily discontinue treatment and administer H1-antihistamines and, if necessary, adrenaline. If the allergic reaction recurs, treatment should be discontinued and not restarted.

- General. [EXCESSIVE SWEATING].

OVERDOSE

Symptoms: Acetylcysteine has been administered to humans at doses of up to 500 mg/kg/24 hours without causing side effects, so the possibility of poisoning due to overdose of this active ingredient can be ruled out. However, in the case of massive ingestion, an intensification of adverse effects, primarily gastrointestinal, is expected. Treatment: Symptomatic treatment should be used. The airways should be kept free of secretions, with the patient lying down and bronchial suctioning performed. If deemed necessary, and if no more than 30 minutes have passed since ingestion, gastric lavage should be performed.

COMPOSITION

ACETYLCYSTEINE: 600 MILLIGRAMS
ASPARTAME (E-951) (EXCIPIENT): 20 MILLIGRAMS
SODIUM SALTS (EXCIPIENT): 137 MILLIGRAMS