Fluimucil Complex 500/200 Mg 12 Effervescent Tablets

Fluimucil Complex (500/200 Mg 12 Effervescent Tablets)

ACTION AND MECHANISM

Combination of an [ANALGESICO] [ANTIPIRETICO] and a [MUCOLITICO].
On the one hand, paracetamol exerts analgesic and antipyretic effects probably due to the inhibition of prostaglandin synthesis at the central level. On the other, acetylcysteine, an N-acetylated derivative of the natural amino acid cysteine, reduces the viscosity of bronchial secretions, favoring its elimination.

INDICATIONS

- Symptomatic relief of [COMMON COLD] and [FLU] that occur with or without fever, mild or moderate pain and thick mucous secretions.

POSOLOGY

DOSAGE:
- Adults and children> 12 years, orally: 1 effervescent tablet / 8-12 h. Maximum dose: 3 tablets / day (600 mg of acetylcysteine).
- Children <12 years: its use is discouraged due to its doses.
Duration of treatment: If the fever, if it exists, persists after 3 days, the other symptoms worsen or persist after 5 days, or other symptoms appear, the clinical situation should be evaluated.

RULES FOR THE CORRECT ADMINISTRATION

Dissolve the effervescent tablet in a glass of water. Do not ingest until bubbling has ceased completely.
It is recommended to drink plenty of liquid during the day.

CONTRAINDICATIONS

- [PARACETAMOL ALLERGY].
- Hypersensitivity to acetylcysteine ​​and other cysteine-related compounds.
- [HEPATOPATIA] (with or without liver failure), viral [HEPATITIS]. Increased risk of hepatotoxicity.

PRECAUTIONS

- [CHRONIC ALCOHOLISM]: Chronic consumption of alcoholic beverages (more than 3-4 alcoholic beverages / day) can enhance the hepatic toxicity of paracetamol. Chronic alcoholics should avoid prolonged treatments or excessive doses of paracetamol (should not be administered more than 2 g / day).
- [ANEMIA]: Due to the presence of paracetamol, the appearance of blood disorders (thrombocytopenia, leukopenia, agranulocytosis, hemolytic anemia, etc.) is possible. Caution is recommended avoiding prolonged treatments. In these patients there is a risk that cyanosis does not manifest despite elevated methemoglobin levels.
- Cardiac or pulmonary alterations. Prolonged treatments will be avoided.
- [RENAL INSUFFICIENCY] severe with creatinine clearance <10 ml / min, the interval between two shots will be at least 8 h. In patients with severe or moderate renal impairment there may be accumulation of conjugated paracetamol derivatives. Prolonged treatments with high doses increase the risk of renal toxicity.
- [ASTHMA]: Bronchospastic reactions have been observed in some asthmatic patients with [SALICILATE ALLERGY] who have taken paracetamol. Although the incidence of cross-reaction is low (less than 5%), clinical control is advised in these patients.
On the other hand, because it contains acetylcysteine, in asthmatic patients with severe [RESPIRATORY INSUFFICIENCY], in those with diseases that occur with [BRONCHIAL SPASM], or with an inadequate capacity to cough, an increase in the fluidity of secretions can lead to an airway obstruction if the expectoration is not adequate. It is therefore recommended to exercise caution.
- [GLUCOSE DEFICIT ANEMIA 6 PHOSPHATE DEHYDROGENASE]: Cases of hemolysis have been observed in patients receiving paracetamol.
- [PEPTIC ULCERA]: Acetylcysteine, by disturbing the digestive mucosa barrier, could increase the risk of gastric bleeding in these patients. It is recommended to extreme precautions.
- Hereditary glutathione deficiency: Acetylcysteine ​​can reduce red blood cell production by increasing glutathione levels.
- At the beginning of the treatment the fluidization and mobilization of the secretions can partially obstruct the bronchi, which will be attenuated throughout the treatment.
- The possible presence of sulfuric odor does not indicate alteration of the preparation, but is typical of acetylcysteine.
- A clinical evaluation should be performed if: if there is a fever, it persists after 3 days, or when the other symptoms get worse or persist after 5 days, or if other symptoms appear.

PRECAUTIONS RELATING TO EXCIPIENTS

- This medicine contains aspartame as an excipient, so it must be taken into account by people affected by [PHENYLKETONURIA]. 100 mg of aspartame correspond to 56.13 mg of phenylalanine.

- This medicine contains sodium salts. To know the exact sodium content, it is recommended to check the composition. Oral and parenteral dosage forms with sodium amounts greater than 1 mmol (23 mg) / maximum daily dose should be used with caution in patients with [RENAL INSUFFICIENCY] or with low sodium diets.

- This medicine contains sorbitol. Patients with hereditary [INTOLERANCE TO FRUCTOSE] should not take this medication.

PATIENT ADVICE

- The patient should be advised to drink plenty of liquid to help with fluidization of secretions.
- The patient should be advised that the preparation may have a slight sulfuric odor, characteristic of acetylcysteine ​​and not of an alteration of the medication.
- It should be noted that the doctor should be informed if a generalized itching appears on the body.
- The presence of paracetamol in the composition of this medicine should be warned. Therefore, other preparations that have this analgesic should not be ingested simultaneously.
- Warn that the maximum dose is 3 tablets daily.
- It is advisable to see a doctor in the following cases: if there is a fever, it persists after 3 days, or when the other symptoms get worse or persist after 5 days, or if other symptoms appear.

SPECIAL WARNINGS

- In case of generalized urticaria or other allergic symptoms, it is recommended to discontinue treatment.
- Chronic alcoholics should avoid prolonged treatments or excessive doses of paracetamol (should not be administered more than 2 g / day).
- At the beginning of the treatment the fluidization and mobilization of the secretions can partially obstruct the bronchi, which will be attenuated throughout the treatment.
- Phenacetin (paracetamol metabolite) can darken urine.

INTERACTIONS

PARACETAMOL:
Paracetamol is metabolized at the liver level, leading to hepatotoxic metabolites, so it can interact with drugs that use the same metabolic pathways. Thus, there are clinical data of interactions at this level with the following drugs:
- Oral anticoagulants (acenocoumarol, warfarin): possible potentiation of the anticoagulant effect, due to possible inhibition of hepatic synthesis of coagulation factors. Given its apparent low clinical relevance, the therapeutic alternative to salicylates is considered when there is anticoagulant therapy. However, the dose and duration of treatment should be as low as possible, with periodic monitoring of the INR.
- Ethyl alcohol: potentiation of paracetamol toxicity, due to possible induction of hepatic production of hepatotoxic products derived from paracetamol.
- Anticholinergics (glycopyrronium, propanteline): decrease in the absorption of paracetamol, with possible inhibition of its effect, due to the decrease in gastric emptying speed.
- Anticonvulsants (phenytoin, phenobarbital, methylphenobarbital, primidone): decreased bioavailability of paracetamol as well as potentiation of hepatotoxicity to overdose, due to the induction of liver metabolism.
- Busulfan: as paracetamol can decrease the available glutathione, the clearance of busulfan can be reduced and its organic levels increased. It is recommended to minimize or avoid administration of paracetamol before (<72 hours) or during treatment with busulfan.
- Chloramphenicol: potentiation of the toxicity of chloramphenicol, due to possible inhibition of liver metabolism.
- Estrogens: decrease in plasma paracetamol levels, with possible inhibition of its effect, due to possible induction of its metabolism.
- Exenatide: the absorption of paracetamol could be diminished by exenatide, as this reduces gastric emptying. This interaction can be avoided if the analgesic is administered 1 hour before exenatide.
- Isoniazide: decrease in paracetamol clearance, with possible potentiation of its action and / or toxicity, by inhibition of its hepatic metabolism.
- Lamotrigine: decrease of the area under a curve (20%) and of the half-life (15%) of lamotrigine, with possible inhibition of its effect, due to possible induction of its hepatic metabolism.
- Propranolol: increase in plasma paracetamol levels, due to possible inhibition of liver metabolism.
- Rifampicin: increased paracetamol clearance due to possible induction of liver metabolism.
In addition, there are clinical data on interactions with other mechanisms:
- Ionic exchange resins (cholestyramine): decrease in the absorption of paracetamol, with possible inhibition of its effect, by fixation of paracetamol in the intestine.

ACETYLCISTEINE:
- Antibiotics: Acetylcysteine ​​may be incompatible with amphotericin B, sodium ampicillin, cephalosporins, erythromycin lactobionate or some tetracyclines. It is recommended to separate the shots at least an interval of two hours.
- Antitussives: Acetylcysteine ​​increases the fluidity of bronchial secretions, so it is not advised to administer it together with cough suppressants, which could inhibit the cough reflex and lead to pulmonary obstruction.
- Bronchial secretion inhibitor drugs (anticholinergics, tricyclic antidepressants, H1 antihistamines, antiparkinsonians, MAOIs, neuroleptics): They can antagonize the effects of acetylcysteine.
- Nitroglycerin: Acetylcysteine ​​may potentiate the vasodilatory effects of nitroglycerin and its adverse reactions at very high doses (100 mg / kg).
- Metal salts: Acetylcysteine ​​could have certain chelating effects of some metals such as gold, calcium or iron, which would decrease its absorption. It is recommended to distance the intake of mineral supplements and acetylcysteine ​​at least two hours.

PREGNANCY

FDA Category B, for both acetaminophen and acetylcysteine.
Regarding paracetamol, no problems have been described in humans. It crosses the placenta. The use of short-term therapeutic oral doses is generally accepted at all stages of pregnancy.
Regarding acetylcysteine, it seems to cross the placental barrier. Data on a limited number of risk pregnancies showed no adverse reactions of acetylcysteine ​​on pregnancy and the health of the fetus or newborn. Studies in some animals show no direct or indirect harmful effects on pregnancy, embryonic / fetal development, childbirth or postnatal development.

Therefore, the administration of this medicine is only accepted if there are no safer therapeutic alternatives, the benefits outweigh the possible risks.

LACTATION

It is recommended to suspend breastfeeding or avoid the administration of this association due to the lack of data on the excretion of acetylcysteine ​​in breast milk, and the effects this could have on the infant.
No problems with paracetamol have been described, although it has been proven that it is excreted with breast milk.

CHILDREN

Due to the doses of this medicine, its use is not recommended in children under 12 years.

ELDERLY

No specific problems have been described in the elderly. However, an increase in the elimination half-life of paracetamol has been observed, so it is normally recommended to reduce the adult dose by 25%. So far it has not been established whether the risk of hepatotoxicity is increased in these patients. On the other hand, in the elderly the presence of liver or respiratory failure is more common, so it is recommended to use acetylcysteine ​​and paracetamol with caution.

EFFECTS ON DRIVING

Acetylcysteine ​​should be used with caution in patients whose activity requires attention and who have observed drowsiness, dizziness or hypotension during treatment with this drug.

ADVERSE REACTIONS

Adverse effects are, in general, infrequent although some may become moderately important.
- Digestive: [NAUSEAS], [VOMITOS], [DIARREA] and [GASTRIC HYPERACITY], gastrointestinal irritation, gastric discomfort.
- Hepatic: rarely, [ICTERICIA], [INCREASE OF TRANSAMINASES], [HEPATOTOXICITY] (associated with cases of paracetamol overdose, either by the intake of 1 toxic dose or several doses of excessive doses).
- Cardiovascular: rarely, [HYPOTENSION].
- Neurological / psychological: [CEFALEA], [TINNITUS], [SOMNOLENCE], [MAREO], gait disturbances.
- Respiratory: [ASTHMA], [BRONCHIAL SPASM], [TOS] excessive that may be due to sudden fluidization and mobilization of secretions, which may partially obstruct the bronchial tubes, chest tightness or respiratory distress, [RINORREA], and more rarely pulmonary hemorrhage; these adverse effects appear most likely in administration by other routes (inhalation). [BRONCHITIS], [TRAQUEITIS], [HEMOPTISIS].
- Genitourinary: paracetamol can cause [NEFROPATIA] which in turn can evolve into a picture of renal failure, [PIURIA] sterile (cloudy urine).
- Allergic / dermatological: [EXANTEMATIC ERUPTIONS], [URTICARY], [PRURITE], [ALLERGIC CONTACT DERMATITIS], [FEVER], [DISNEA], [ANGIOEDEMA].
- Ophthalmological: [VISION DELETE].
- Hematologic: [TROMBOCITOPENIA], [LEUCOPENIA], [PANCITOPENIA], [NEUTROPENIA], [AGRANULOCITOSIS] and [HEMOLITIC ANEMIA].
- Metabolic: exceptionally, [HYPOGLUCEMIA], especially in children.
- General: [HYPERHIDROSIS].

OVERDOSE

PARACETAMOL:

- Symptoms: dizziness, vomiting, loss of appetite, jaundice and abdominal pain. If an overdose has been ingested, you should go quickly to a medical center even if there are no symptoms, since these, very serious, usually manifest on the third day after ingestion.
Overdosing is evaluated in four phases, which begin at the time of ingestion of the overdose: Phase | (12-24 h): nausea, vomiting, diaphoresis, anorexia; Phase II (24-48 h): clinical improvement, the levels of AST, ATL, bilirubin and prothrombin begin to rise; Phase III (72-96 h): hepatotoxicity peak, values ​​of 20,000 for AST may appear; Phase IV (7-8 days): recovery.
Paracetamol overdose is considered, the ingestion of a single intake of more than 6 g in adults and 100 mg / kg in children. Doses greater than 20-25 g are potentially fatal. Hepatotoxicity symptoms include nausea, vomiting, anorexia, malaise, diaphoresis, abdominal pain and diarrhea. Hepatotoxicity does not manifest until 48-72 hours after ingestion. Patients in treatment with chronic barbiturates or alcoholics may be susceptible to the toxicity of an overdose of paracetamol.

- Treatment: in all cases, gastric aspiration and lavage will be performed, preferably within 4 hours after ingestion.
* Specific antidote: N-acetylcysteine ​​300 mg / kg (equivalent to 1.5 ml / kg of 20% aqueous solution) via iv for 20 h 15 min according to the following scheme:
I) Adults: Attack dose: 150 mg / kg iv slowly or diluted in 200 ml of 5% glucose for 15 minutes. Maintenance: initially 50 mg / kg in 500 ml of 5% glucose in slow infusion for 4 h; subsequently, 100 mg / kg in 1000 ml of 5% glucose iv infusion for 16 h.
II) Children: The period in which the treatment offers the greatest guarantee of efficacy is within 8 hours of ingesting the overdose. The effectiveness decreases progressively after 8 hours, being ineffective after 15 hours of intoxication. The volume of the 5% glucose solution for infusion should be adjusted to the age and weight of the child.
The administration of the 20% N-acetylcysteine ​​solution will be interrupted when the paracetamol plasma concentrations are below 200 mcg / ml.
Adverse effects of N-acetylcysteine ​​IV: exceptionally, rashes and anaphylaxis have been observed, generally 15 min-1 h since the beginning of the infusion.
N-acetylcysteine ​​by mouth: it must be administered within 10 hours after overdosing. The recommended dose for adults is: initial dose of 140 mg / kg body weight followed by 17 doses of 70 mg / kg body weight, one every 4 hours. Each dose should be diluted to 5% with a cola drink, grape juice, orange juice or water, before being administered, due to its unpleasant smell and its irritating or sclerosing properties. If the dose is vomited within one hour after administration, it should be repeated. If necessary, the antidote (diluted with water) can be administered by duodenal intubation.

ACETYLCISTEINE:

- Symptoms: Acetylcysteine ​​has been administered in man at doses up to 500 mg / kg / 24 hours without causing side effects, so it is possible to exclude the possibility of poisoning by overdosing of this active substance. However, in case of massive ingestion, the appearance of an intensification of adverse effects, mainly of the gastrointestinal type, is expected.

- Treatment: Symptomatic treatment will be used. The airways will be kept free of secretions, laying the patient down and practicing bronchial aspiration. If deemed necessary, and no more than 30 minutes have elapsed after ingestion, gastric lavage will be performed.

Leaflet Fluimucil Complex 500/200 Mg 12 Effervescent Tablets