SOBREPIN TOSSE INFLUENCE REFLUDEDORE 650 MG/ 20 MG/ 4 MG FREE FOR ORAL DEOLUTION
active ingredients
Qualitative and quantitative composition Each bag contains: - Paracetamol 650 mg; - Malato Clorfenamin 4 mg (equivalent to 2.80 mg of chlorfenamine); - Destrometorphan bromished 20 mg.
Excipient/i with known effects Each bag contains: 4,4 g sucrose, 0.003 mg orange yellow S (E-110) and 23,6 mg of partner. For the full list of excipients, see paragraph 6.1.
Excellent
Titanium dioxide (E-171), Citric acid anidro, Sodium saccharin, Sodium cyclamate, Polysorbate 80, Sodium citrate, Povidone K 30, Lemon Aroma, Chinoline Yellow (E-104), Orange Yellow S (E-110).
Therapeutic indications
Treatment of symptoms of common flu and cold, accompanied by mild to moderate pain, fever, dry cough (irritative cough, nervous cough) and nasal congestion in adults and adolescents from 14 years of age.
Contraindications
- Hypersensitivity to active ingredients or any of the excipients listed in paragraph 6.1; - Asthmatic cough; - Production cough; - Respiratory failure; - Renal or severe liver failure. - Concurrent therapy or in the previous two weeks, with one of the following medicines: • Antidepressants inhibitors of monoamine oxidase (IMAO): the concomitant use of dextromethtorphan and IMAO involves the risk of serotonergic syndrome. Concurrent intake of these medicines can cause increased blood pressure and hypertensive crisis (see paragraph 4.5), • Selective serotonin reuptake inhibitors (SSRI), • Bupropion, • Linezolide, • Procarbazine, • Selegilina; - Children under 14 years of age.
Population
Population Adults and teenagers aged 14 years: a sachet (containing 650 mg of paracetamol) every 6 - 8 hours (3 or 4 times a day), depending on the need. It is recommended to take a dose before going to sleep. Do not take more than 4 sachets per day (equal to 2.6 g of paracetamol). (Consulting in paragraph 4.4). If the patient gets worse or symptoms persist after 5 days of treatment in adults or 3 days of treatment in adolescents or if the fever persists for over 3 days, assess the clinical situation.
Pediatric population: Children under 14 years of age cannot take this medication, due to the dosage of the active substances contained.
Patients with liver failure: In case of liver failure, do not take more than 3 sachets per day (2 g of paracetamol).The minimum interval between doses must be eight hours.
Patients with kidney failure: In case of kidney failure, the dose must be reduced, depending on the glomerular filtration level, on the basis of the following table:
| Glomerular Filtration | Dosage |
| 10-50 ml/min | 500 mg every 6 hours |
| | 500 mg every 8 hours |
Method of administration Oral use. Pour the contents of a sachet into a glass and add half a glass of water about. Mix until the granules are dissolved. You can add sugar or honey, depending on your preferences. If the medicine is taken in the evening, it is advisable to take it before going to sleep.
Conservation
Do not store at temperature above 30°C.
Warnings
Do not exceed the recommended daily dose.
Relative to the paracetamol It is recommended to evaluate the clinical picture: - In patients with liver disease (with or without liver failure) or life hepatitis, since the risk of hepatotoxicity has increased (see paragraph 5.2); - In patients with anemia, cardiopathy or lung disease and kidney dysfunction (in the last case, occasional use is acceptable, but prolonged intake of high doses can increase the risk of adverse events to the kidneys); - In asthmatic patients, sensitive to acetylsalicylic acid, since bronchospastic reactions with paracetamol (cross reaction) have been reported in these patients, although these effects have only occurred in 5% of patients tested. Intake of drugs containing paracetamol by patients who regularly consume alcoholic beverages (three or more alcoholic beverages, such as beer, wine or liquor, daily) could cause liver damage. Chronic alcoholics should consult a doctor before taking paracetamol, other analgesics or other antipyretics. Chronic alcoholics must not take more than 2g/day of paracetamol. Avoid taking this medicine at the same time as other drugs containing paracetamol. Where other drugs containing paracetamol are taken, the maximum paracetamol dose of 3 g per day should not be exceeded, considering the paracetamol content of all the medicines used. The toxic effects associated with paracetamol may occur as a result of a single overdose or as a result of more excessive doses of paracetamol. In very rare cases, cases of generalized acute acute exantelosis (AGEP), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were reported in association with the intake of paracetamol. Patients should be informed of symptoms of severe skin reactions and treatment should be interrupted to the first sign of skin rash or hypersensitivity. Taking a dose higher than the recommended dose (surplus) can cause liver damage. An immediate medical consultation is essential both in adults and children, although no sign or symptom is noted.
Relative to malato chlorfenamine Caution should be used in patients suffering from hypertension, glaucoma, obstruction of the vescic neck, hyperthyroidism and prostate hyperplasia with residual urine formation. It is recommended to evaluate the clinical situation before administering this medicine to patients suffering from chronic respiratory diseases such as emphysema, chronic bronchitis, bronchial asthma or cough accompanied by excessive secretions. It is recommended to evaluate the clinical picture before administering this medicine to allergic patients to other antihistamines, as cross-sensitivity may occur. This medicine may cause drowsiness. In children and elderly treated with antihistamines a paradox reaction can occur characterized by hypereccitability. Older patients may be more sensitive to anticholinergic effects of antihistamines, such as dizziness, sedation, confusion, hypotension, dry mouth. Patients taking this medicine should avoid concurrent consumption of alcoholic beverages. Consult a doctor or pharmacist before taking substances that depress the central nervous system (see paragraph 4.5). Chlorfenamine can exacerbate the sedative effects of substances that depress the central nervous system, such as alcohol, sedatives and tranquilizers.
Relative to the rightmetorphan In patients with liver disease, the metabolism of the dextromethtorphan could be altered and this should be taken into account when setting the dosage for these patients. The rightmetorphan is metabolized by the liver cytochrome P450 2D6. The activity of this enzyme is genetically determined. About 10% of the general population slowly metabolizes CYP2 D6. Slow metabolizers and patients taking CYP2D6 inhibitors at the same time may experience increased or prolonged effects of dextromethtorphan. Therefore, caution should be used in patients with slow CYP2D6 metabolism or taking CYP2D6 inhibitors (see also paragraph 4.5). Do not administer sedated, debilitated or breasted patients. It is recommended for patients with chronic respiratory problems, such as emphysema, chronic bronchitis, bronchial asthma or a condition that causes cough accompanied by excessive secretions, glaucoma or urinary difficulties caused by prostatic hyperplasia, to consult a doctor before taking this product. Dextromethtorphan intake may be associated with istamine release and, consequently, should be avoided in patients with atopic dermatitis. Cases of detachment were reported. Use caution especially in teenagers and young people, as well as in patients with drug abuse or psychoactive substances.
Serotonergic syndrome Serotonergic effects have been reported, including the development of a potentially lethal serotonin syndrome, in the face of the concomitant intake of dextromethtorphan and serotonergic agents, such as selective inhibitors of serotonin reuptake (SSRI), drugs that affect serotonin metabolism (including inhibitors of oxidase monoamines (IMAO) and in inhibitors YY.6. Serotonin syndrome can cause mental state alterations, autonomic instability, neuromuscular abnormalities and/or gastrointestinal symptoms. If you suspect the presence of serotonin syndrome, stop taking SOBREPIN TOSSE INFLUENCE REFREDDORE.
Warnings on excipients Patients suffering from rare hereditary problems of fructose intolerance, glucose-galactose mal absorption or sucrasis-isomaltase failure should not take this medicine. This medicine contains 4.4 g sucrose per dose; this aspect must be taken into account in patients with diabetes mellitus. This medicine may cause allergic reactions since it contains orange yellow S (E110). This medicine contains 26.3 mg of sodium equivalent to 1.18% of the maximum daily intake recommended by the WHO which corresponds to 2 g sodium for an adult.
Interactions
Interactions due to paracetamol Paracetamol is metabolized largely in the liver and therefore can interact with other drugs that use the same metabolic pathways or act inhibiting or inducing such ways. Some of its metabolites are hepatotoxic and, consequently, the concomitant administration of powerful enzymatic inductors (refampycin, some anticonvulsants, etc.) can cause hepatotoxic reactions, especially in the face of the intake of high doses of paracetamol. Potentially risky interactions include: - Oral anticoagulants (acenocumarol, warfarin): possible strengthening of the anticoagulant effect due to the inhibition of the liver synthesis of coagulation factors. However, in the light of the seemingly low clinical relevance of this interaction in most patients, we consider alternative analgesic therapies based on salicylates where an anticoagulant therapy is available, In any case, the dose and duration of treatment must be as low as possible and accompanied by regular INR monitoring. Patients should be explained to consult a doctor or pharmacist before use, if they take an anticoagulant such as warfarin or other derivative of cumarin. - Ethiopian alcohol: strengthening of the toxicity of the paracetamol, through possible induction of the hepatic production of hepatotoxic by-products of the paracetamol. - Anticonvulsants (fenitoin, phenobarbital, methylfenobarbital, primidone): decreased bioavailability of paracetamol and exacerbation of hepatotoxicity against overdose, caused by the induction of liver metabolism. - Auction diuretics: possible reduction of the effects of diuretics, since the paracetamol could reduce the kidney excretion of prostaglandins and plasma kidney activity. - Isoniazide: reduced clearance of the paracetamol, with possible strengthening of its action and/or toxicity, due to the inhibition of its liver metabolism. - Lamotrigine: reduced bioavailability of lamotrigine, with possible reduction of its effect, due to the possible induction of its liver metabolism. - Metoclopramide and domperidone: increased paracetamol absorption in the small intestine, due to the effect of these drugs on gastric emptying. - Probenecid: Increased plasma half-life of paracetamol by reducing urinary degradation and excretion of its metabolites. - Propranolo: increased plasma levels of paracetamol, due to the possible inhibition of its liver metabolism. - Ion exchange resins (colysmine): reduced absorption of the paracetamol, with possible inhibition of its effects, due to the fixing of the paracetamol in the intestine.
Interactions due to malato chlorfenamine - Alcoholics or drugs that depress the central nervous system: the depressive effect of such substances or antihistamine effects could be enhanced and cause overdose symptoms. - Monoamine oxidase inhibitors (IMAO), including furazolidone (antibacterial) and procarbazine (antincro): we do not recommend concurrent intake because they could prolong and intensify the anti-linergical and depressive effects of the central nervous system of antihistamines. - Antidepressants triceclic or maprotiline (tetracyclic antidepressants) or other anti-linergic drugs: anticholinergic effects of these medicines or antihistamines such as chlorfenamine could be enhanced. In the case of gastrointestinal problems, patients should be advised to consult the doctor as soon as possible, as paralytical may occur (see paragraph 4.4). - Ototoxic drugs: Symptoms of ototoxicity such as tinnitus, head turns and dizziness could be masked. - Photosensitizing medicines: additional photosensitizing effects may occur.
Interactions due to the right: - NSAID COX-2 inhibitors (Coxib). Pharmaccinetic studies have shown that plasma concentrations of dextromethtorphan can increase if the drug is administered in conjunction with celecoxib, parecoxib or valdecoxib, due to the inhibition of the liver metabolism of the dextromethtorphan. - Antiarrhythmics (myodarone or chinidine). There may be an increase in plasma concentrations of dextromethtorphan and toxic levels may be reached. You may need to adjust the dosage. - CYP2D6 inhibitors: The dextromethtorphan is metabolized by CYP2D6 and has a high metabolism of the first step. Concurrent use of powerful inhibitors of the CYP2D6 enzyme can increase the concentrations of dextromethtorphan in the body, up to levels many times higher than normal. This increases the risks that the patient manifests the toxic effects of dextromethtorphan (acting, confusion, tremor, insomnia, diarrhea and respiratory depression), as well as serotonergic syndrome. Fluoxetine, paroxetine, chinidine and terbinaphine are powerful inhibitors of the CYP2 enzyme D6. The plasma concentrations of dextromethtorphan increase up to 20 times with the concurrent intake of chinidine, which exacerbates the adverse effects of the drug on the central nervous system. Amiodarone, flecainide, propafenone, sertralin, bupropion, methadone, cinacalcet, aloperidol, perfenazine and thiodazine also produce similar effects on the metabolism of the dextromethtorphan. If the concomitant use of CYP2D6 inhibitors and dextromethtorphans is necessary, the patient must be monitored and it may be necessary to reduce the dose of dextromethtorphan. - Antidepressants of monoamine oxidase inhibitors (IMAO), such as moclobemide and tranilcypromine; selective serotonin reuptake inhibitors (SSRI), such as fluoxetine and paroxetine; serotonergic as bupropion and other monoamine oxidase inhibitors (IMAO), such as procarbazine, selegiline and antifungal and antibacterial linezolide: serious adverse reactions, characterized by serotonergic syndrome with excitement, sweat, rigidity and hypertension. This could be caused by the inhibition of the liver metabolism of the dextromethtorphan. As a result, it is recommended to avoid the association with such drugs and not to administer the rightmetorphan until at least 14 doses have passed from the treatment with the medicines described above. - Depressive drugs of the central nervous system, including psychotropics, antihistamines or medicines for Parkinson's disease: possible strengthening of the effects of depression of the central nervous system. - Inspectorates and mills. Inhibition of cough reflex may cause pulmonary obstruction in case of increased volume or fluidity of bronchial secretions. - Aloperidol: since it inhibits CYP2D6, it can increase the plasma levels of dextromethtorphan, causing a possible exacerbation of its adverse effects. - Alcohol consumption during treatment with dextromethtorphan may increase the incidence of adverse events; consequently, it is recommended not to consume alcoholic beverages during treatment. - Do not administer together with grapefruit or bitter orange juice, as these drinks may result in an increase in the plasma levels of dexterphan by inhibiting the cytochrome P-450 (CYP2D6 and CYP3 A4).
Interactions with clinical analysis - Paracetamol may alter the results of the following clinical analyses: • Blood: increase (biological) of transaminase (ALT and AST), alkaline phosphatease, ammonia, bilirubin, creatinine, lactic dehydrogenase (LDH) and urea; increase (analytic interference) of glucose, theophylline and uric acid. Increased protrombine time (in patients taking a maintenance dose of warfarin, but not clinically significant). Reduction (analytic interference) of glucose when using the method of oxydasis-peroxidase. • Urine: falsely increased values of methylpinephrine and uric acid can be found. • Pancreatic function test with bentiromide: paracetamol, such as bentiromide, paracetamol, like bentiromide, is metabolized in an arylamine, and therefore the apparent amount of paraaminobenzoic acid (PABA) recovered has increased; it is recommended to suspend the intake of paracetamol at least three days before the administration of bentiromide. • urinary determinations of 5-hydroxy-ndolacetic acid (5-HIAA): paracetamol can cause false positive results in qualitative screening tests that use naphthal nitrose as reagent. The quantitative test remains unchanged. • Chlorfenamine can interfere with the skin tests performed with allergen extracts, so it is recommended to suspend taking the medicine at least three days before testing.
Effects
Security based on clinical trial data Clorfenamin The safety of chlorphenamine, as shown by clinical trials, is based on the data of six randomized clinical trials, with placebo control, conducted for the treatment of seasonal or non-seasonal allergic rhinitis. Table I lists the adverse reactions occurring, where more than one case has been reported, the incidence was higher than that found with the placebo and the adverse reaction occurred in at least 1% of patients.
Table 1 Reactions reported in ≥ 1% of subjects treated with chlorfenamine in six randomized clinical trials with placebo control. | Classification of organs | Clorfenamin 12-24 mg/day (N=401) % (frequency) | Placebo (n=387) |
| Disorders of the nervous system |
| Dizziness, sleep | 4.5 (frequent) | 3,1 |
| 28,9 (very frequent) | 11,9 |
| Gastrointestinal disorders |
| Dry mouth, despair, pharyngitis | 5.5 (frequent) | 1,8 |
| 1.0 (frequent) 2.5 | 0,3 |
| (frequent) | 1,0 |
| General disturbances and disturbances at the administration site |
| Restlessness | 3.2 (frequent) | 2,1 |
Post-commercial data The following tables list the adverse reactions found in the period following the marketing for the dextromethtorphan (tabelle 2 and 3) and the paracetamol (tabelle 4 and 5). The frequency is shown on the basis of the following convention: - Very common (≥1/10); - Municipality (≥1/100 and Destrometorfano In Table 2, adverse reactions to the dextromethtorphan are presented by frequency category, on the basis of the incidence found in clinical trials or in any epidemiological studies, or, where the incidence is not available, the frequency category is indicated as
don't notice. In Table 3, the same adverse reactions are presented by frequency category, based on spontaneous reports.
Table 2 Adverse reactions to the dextrometorphan found in the post-commercialization period by frequency category, calculated on the basis of clinical trials or epidemiological studies | Gastrointestinal disorders |
| Notable | Abdominal pain |
| Notable | Diarrea |
| Notable | Nausea |
| Notable | Vote |
| Immunity disorders |
| Notable | Angioedema |
| Notable | Prudence |
| Notable | Rash |
| Notable | Orticaria |
| Disorders of the nervous system |
| Notable | Heads |
| Notable | Psychological hyperactivity |
| Notable | Sleep |
| Psychiatric disorders |
| Notable | Insomnia |
Table 3 Reactions adverse to the dextrometorphan found in the post-commercialization period by frequency category, calculated on the basis of spontaneous reports | Gastrointestinal disorders |
| Very rare | Abdominal pain |
| Very rare | Diarrea |
| Very rare | Nausea |
| Very rare | Vote |
| Immune system disorders |
| Very rare | Angioedema |
| Very rare | Prudence |
| Very rare | Rash |
| Very rare | Orticaria |
| Disorders of the nervous system |
| Very rare | Heads |
| Very rare | Psychological hyperactivity |
| Very rare | Sleep |
| Psychiatric disorders |
| Very rare | Insomnia |
Paracetamol In Table 4, adverse reactions to paracetamol are presented by frequency category, on the basis of the incidence found in clinical trials or in any epidemiological studies, or, where the incidence is not available, the frequency category is indicated as
don't notice. Table 4: Paracetamol adverse reactions found in post-commercialization period by frequency category, calculated on the basis of clinical trials or epidemiological studies | Additional analysis |
| Notable | Increase in transaminasis1 |
| Immune system disorders |
| Notable | Anaphylactic reaction |
| Notable | Hypersensitivity |
| Disorders of skin and subcutaneous tissues |
| Notable | Orticaria |
| Notable | Rash with itching |
| Notable | Rash |
1 Increased levels of transaminers may occur in some patients taking therapeutic doses of paracetamol; this is not accompanied by liver damage and usually returns to normality with the continuation or interruption of treatment based on paracetamol. In Table 5, the same adverse reactions are presented by frequency category on the basis of spontaneous reports.
Table 5: Paracetamol adverse reactions found in post-commercialization period by frequency category, calculated on the basis of spontaneous signals 1 | Additional analysis |
| Very rare | Increase in transaminasis |
| Immune system disorders |
| Very rare | Anaphylactic reaction |
| Very rare | Hypersensitivity |
| Skin and subcutaneous tissue disorders |
| Very rare | Orticaria |
| Very rare | Rash with itching |
| Very rare | Rash, serious skin reactions have been reported |
1 The estimate of patients exposed was calculated on the basis of data obtained by IMS MIDAS. 2 Increased levels of transaminers may occur in some patients taking therapeutic doses of paracetamol; this is not accompanied by liver damage and usually returns to normality with the continuation or interruption of treatment based on paracetamol. Simultaneous consumption of alcohol during treatment may increase the incidence of side effects. It is recommended not to consume alcoholic beverages during treatment. Where adverse reactions were noted, suspend treatment and report the event to the pharmacovigilance body.
Reporting of suspicious adverse reactions The reporting of suspicious adverse reactions that occur after the authorization of the medicinal product is important, as it allows continuous monitoring of the benefit/risk ratio of the medicinal product. Healthcare workers are required to report any suspected adverse reaction through https://www.aifa.gov.it/content/segnalazioni-reazioniavverse.
Overdosing
Adverse reactions associated with overdose of the combination of chlorphenamine, dextromethtorphan and paracetamol were not observed in the revision of post-commercialization security data or literature. The information below describes the effects of overdose for each of the active ingredients.
Clorfenamin Symptoms of clorfenamine overdose may include: central nervous system depression, hyperthermia, anti-linergical syndrome (midriasis, vampires, fever, dry mouth, urine retention, reduction of intestinal noise), tachycardia, hypotension, hypertension, nausea, vomiting, agitation, confusion, hallucinations, psychosis, seizures or arrhythmias. In rare cases, patients with agitation, coma or prolonged seizures can develop rhabdomiolisis and kidney failure.
Destrometor Table 6 shows the symptoms of the overdose of dextromethtorphan reported in literature.
Table 6 Symptoms of the overdose of dexterphan reported in literature | System of classification of organs | Action against |
| Psychiatric disorders | Agitation, confusing state, Conversion disorders, hallucinations |
| Disorders of the nervous system | Atassia, Goffaggine, Coma, Disartria, Letargia, Nistagmo, Convulsioni, Syndrome serotonergica, Tremore |
| Ocular disorders | Miosi, Midriasi |
| Respiratory disorders, chests and mediastinal disorders | Respiratory depression |
| Renal and urologic disorders | Urine retention |
| Hepatobiliary disorders | |
Paracetamol In the case of prolonged release paracetamol products or where the exact formulation is not known, it is recommended to remix plasma levels of paracetamol 4-6 hours after the first measurement, since these levels continue to increase with prolonged release products and can affect therapeutic decisions. In adults and adolescents (≥12 years of age), hepatotoxicity may occur after ingestion of a dose greater than 7.5-10 g in a period of 8 hours or less. Death is a rare event (less than 3-4% of untreated cases) and has rarely been reported with overdose less than 15 grams. In children (
Table 7: Adverse reactions found following overdose of paracetamol | Metabolic disorders and nutrition |
| Lack of appetite |
| Gastrointestinal disorders |
| Vomito, nausea, abdominal pain |
| Hepatobiliary disorders |
| Hepatic necrosis, acute liver failure, jaundice, hepatomegalia, liver dolorability |
| General disturbances and alterations at the administration site |
| Pallore, hyperhidrosis, malaise |
| Additional analysis |
| Increased bilirubin, increased liver enzymes, increased INR, protrombine time extension, increased phosphate and lactate levels in the blood. |
Evaluation of paracetamol overdose Paracetamol overdose is evaluated in four stages, starting with overdose ingestion: - Phase I (12-24 hours): nausea, vomiting, diaphoresis and anorexia; - Phase II (24-48 hours): clinical improvement; aST and ALT levels begin to rise, bilirubin and protrombine; - Phase III (72-96 hours): peak of hepatotoxicity; aST values are 20,000; - Phase IV (7-8 days): recovery. In the event of an overdose ingestion, the patient must be treated in time at a health facility, even if it does not have significant signs or symptoms, since, albeit deadly, they often do not appear immediately after ingestion, but only after the third day. Hepatic necrosis may cause death. Acute kidney failure may also occur.
In adults and adolescents (from 12 years of age), hepatotoxicity may occur after ingestion of a dose of 7.5-10 g in a period of 8 hours or less. Death is a rare event (less than 3-4% of untreated cases) and have rarely been reported overdose in the face of a quantity less than 15 grams.
In children (up to 12 years old), acute ingestion of less than 150 mg/kg, was not associated with hepatotoxicity. Symptoms of hepatotoxicity can occur in the form of nausea, vomiting, anorexia, malaise, diaphoresis, abdominal pain and diarrhea. Hepatotoxicity is not evident until 48-72 hours have passed since ingestion. If the ingested dose is more than 150 mg/kg or if it is not possible to determine the ingested quantity, it is recommended to take a serum paracetamol sample 4 hours after ingestion. In case of hepatotoxicity, perform a liver function test and then repeat it at intervals of 24 hours. Hepatic failure can cause encephalopathy, coma and death. Plasma levels of paracetamol exceeding 300 mcg/ml, measured 4 hours after ingestion, were associated with liver damage in 90% of patients. The liver damage begins when the paracetamol levels at 4 hours are less than 120 mcg/ml, or less than 30 mcg/ml 12 hours after ingestion. Chronic ingestion of doses greater than 4 g/day can cause transient hepatotoxicity. Tubular necrosis of the kidneys may occur and damage to myocardial. The following table lists clinical reactions considered sequel to acute liver failure, which can be lethal. These reactions can be considered predictable when they occur in the face of acute liver failure associated with paracetamol overdose.
Table 8: The predicted sequence of acute liver failure associated with paracetamol overdose | Infections and infestations |
| Sepsis, mycotic infections, bacterial infections |
| Blood and lymphatic disorders |
| Intravascular coagulation scattered, coagulopathy, thrombocytopenia |
| Metabolic disorders and nutrition |
| Hypoglycemia, hypophosphateemia, metabolic acidosis, lactic acidosis |
| Disorders of the nervous system |
| Coma (from massive overdose of paracetamol or overdose of multiple drugs), encephalopathy, brain edema |
| Heart disorders |
| Cardiomyopathy |
| Vascular disorders |
| Hypotension |
| Respiratory disorders, chests and mediastinal disorders |
| Respiratory failure |
| Gastrointestinal disorders |
| Pancreatitis, gastrointestinal hemorrhage |
| Renal and urinary disorders |
| Acute kidney failure |
| General disturbances and alterations at the administration site |
| Multi organ insufficiency |
Treatment of paracetamol overdose In all cases, gastric suction and lavender must be performed, preferably within four hours of ingestion. There is a specific antidote for toxicity
paracetamol: the
N-acetylcysteine. Endovenous administration of 300 mg/kg is recommended
N-acetylcysteine (equivalent to 1.5 ml/kg aqueous solution at 20%; pH 6,5) on a 20-hour span and 15 minutes, as described below:
Adults - Attack doses: 150 mg/kg (equivalent to 0.75 ml/kg aqueous solution at 20% of Nacetilcisteina; pH: 6.5), slowly administered by intravenous or diluted in 200 ml of dextrose 5%, within 15 minutes. - Maintenance doses: a) Initially 50 mg/kg (equivalent to 0.25 ml/kg aqueous solution at 20% of Nacetilcisteina; pH: 6,5) in 500 ml of dextrose 5%, to be administered by slow infusion in 4 hours. b) Subsequently, 100 mg/kg (equivalent to 0.50 ml/kg aqueous solution at 20% N-acetylcysteine; pH: 6,5) in 1000 ml dextrose 5%, to be administered by slow infusion in 16 hours.
Children The volume of the dextrose solution at 5% per infusion must be adapted according to the age and weight of the child, to avoid pulmonary vascular congestion. The effectiveness of the antidote is maximum when administered within eight hours of poisoning. Efficacy gradually decreases from the eighth now on and the antidote is no longer effective 15 hours after poisoning. The administration of the aqueous solution at 20% of N-acetylcysteine can be suspended when the results of the analysis show levels of paracetamol in the blood below 200 mcg/ml.
N-acetylcysteine adverse reactions for ev In exceptional cases, skin rash and anaphylaxis were observed, usually between 15 minutes and an hour from the beginning of the infusion.
N-acetylcysteine administration by mouth N-acetylcysteine antidote must be administered within ten hours of overdose, The recommended dose of antidote for adults is: - An initial dose of 140 mg per kg body weight; - 17 doses of 70 mg per kg body weight, every 4 hours. Each dose must be diluted at 5% with a cola-based drink, grapefruit juice, orange juice or water before administration, due to its unpleasant smell and its irritating or sclerosating properties. In case the patient vomits the dose within an hour of administration, this should be repeated. If necessary, the antidote (diluted with water) can be administered through duodenal intubation.
Blood and lymphatic disorders: hemolytic anemia was reported in patients with G6PD deficiency (glucose-6-phosphate dehydrogenase) during paracetamol overdose.
The medicine should not be taken during pregnancy and breastfeeding.
Pregnancy
There are no adequate controlled studies on pregnant women or breastfeeding related to the combination of clorfenamine, dextromethtorphan and paracetamol. This product should not be used during pregnancy or breastfeeding, unless the potential benefits in terms of mother care are greater than the potential risks for fetus or infant.
Paracetamol: The paracetamol given to the mother in controlled doses crosses the placenta and enters the fetal circulation 30 minutes after ingestion and is efficiently metabolized through fetal sulphoconjugation. When taken as recommended, the paracetamol does not adversely affect the pregnant woman or fetus. Reproductive studies have not shown malformations or phototoxic effects. Epidemiological data relating to oral intake of therapeutic doses of paracetamol do not show undesirable effects on pregnant woman, fetus or infant. Epidemiological studies on the neurological development of children exposed to paracetamol in the maternal uterus have reported inconclusive results. A large amount of data on pregnant women indicates the absence of fetal and neonatal toxicity or congenital malformations. If clinically necessary, paracetamol can be taken in pregnancy, however it should be used at the lowest effective dose and for as short as possible and as frequently as possible.
Malfunctional Clorfenamin: It is not known whether chlorfenamine or its metabolites cross the placenta. No teratogenic effects have been demonstrated in animal studies, but there have been reduced postnatal survival rates compared to those used clinically (see paragraph 5.3).
Destrometorfano: There are no controlled and adequate studies in human beings. However, the use of this medicinal product may be acceptable in the absence of safer therapeutic alternatives and always that the benefits are higher than the potential risks. Animal studies have not shown reproductive toxicity (see paragraph 5.3).
Breastfeeding
Paracetamol: Paracetamol is excreted in breast milk in low concentrations (from 0.1% to 1.85% of the dose ingested by the mother). Maternal ingestion of paracetamol, in controlled doses, does not involve risks to the newborn. Although maximum concentrations were found between 10 and 15 mcg/ml (from 66.2 to 99.3 mcmoles/l) in breast milk, one or two hours from the mother’s intake of a single dose of 650 mg, the paracetamol and its metabolites were not detected in infant urine. The half-life in breast milk is between 1.35 and 3.5 hours. No adverse events have been reported in children.
Malfunctional Clorfenamin: Since small quantities of antihistamines are excreted in the maternal lact, there is the risk of adverse events in the newborn, as a state of unusual excitement. Chlorfenamine can inhibit breastfeeding due to its anti-linergical action.
Destrometor There are no data available on the excretion of the dextromethtorphan in breast milk, even if there were no problems in humans.
Fertility
Male fertility alterations have been reported with paracetamol in the face of higher amounts of clinical doses (see paragraph 5.3). There are no human data available.
Source: Farmadati
