Instructions Gripout tablets strip No. 4
Composition
active ingredients: 1 tablet contains paracetamol 500 mg, chlorpheniramine maleate 2 mg, phenylephrine hydrochloride 5 mg, caffeine anhydrous 15 mg;
excipients: corn starch, lactose monohydrate, methylparaben (E 218), propylparaben (E 216), sodium starch glycolate (type A), magnesium stearate, talc, tartrazine (E 102), povidone K-30.
Dosage form
Pills.
Main physicochemical properties: tablets are round, flat, yellow in color, inclusions are allowed, with a break line on one side.
Pharmacotherapeutic group
Analgesics and antipyretics. Anilides. Paracetamol, combinations without psycholeptics. ATX code N02B E51.
Pharmacological properties
Pharmacodynamics
Combined drug. Paracetamol blocks cyclooxygenase, which leads to the cessation of prostaglandin synthesis, exhibits antipyretic and analgesic effects. Chlorpheniramine maleate blocks H-1-histamine receptors. It exhibits antiallergic and anti-edematous effects. It helps reduce the permeability of the vessels of the mucous membrane of the upper respiratory tract, eliminates swelling and hyperemia of the nasal mucosa, suppresses the symptoms of allergic rhinitis, and facilitates breathing. Phenylephrine hydrochloride is a stimulant mainly of alpha-1-adrenoreceptors. It has a vasoconstrictor effect, mainly on the vessels of the upper respiratory tract, reduces increased mucus production and thus helps eliminate nasal congestion. Caffeine has a stimulating effect on the central nervous system, enhances the analgesic effect of paracetamol, reduces fatigue and drowsiness, and increases physical and mental performance.
Pharmacokinetics
Paracetamol is rapidly and almost completely absorbed from the digestive tract, mainly in the small intestine. After a single dose of 500 mg, the maximum concentration in the blood plasma is reached after 10-60 minutes. Paracetamol is rapidly and evenly distributed in most tissues of the body. About 25% of paracetamol in the blood binds to plasma proteins. Paracetamol is metabolized by the microsomal enzyme system in the liver. About 80-85% of paracetamol in the body is conjugated mainly with glucuronic acid and to a lesser extent with sulfuric acid. The half-life is 1-3 hours. Paracetamol is excreted in the urine mainly in the form of paracetamol glucuronide with small amounts of paracetamol sulfate and mercaptate and in unchanged form.
Phenylephrine is unevenly absorbed from the digestive tract and is easily metabolized. After oral administration, its effect occurs after 15-20 minutes and persists for 2-4 hours. The bioavailability of phenylephrine is low. Phenylephrine is biotransformed in the intestinal wall during absorption and in the liver. Less than 16% of the administered dose is excreted unchanged together with metabolites almost completely in the urine.
Chlorpheniramine is absorbed relatively slowly from the gastrointestinal tract, peak plasma concentrations are reached 2.5-6 hours after oral administration. Its bioavailability is low (25-50%). Chlorpheniramine undergoes significant first-pass metabolism. About 70% of chlorpheniramine in the systemic circulation is bound to plasma proteins. The half-life ranges from 2 to 43 hours. Chlorpheniramine is widely distributed in the body, penetrates the central nervous system. Chlorpheniramine is actively metabolized. Metabolites include desmethyl and didesmethyl chlorpheniramine. Unchanged chlorpheniramine and metabolites are excreted mainly in the urine. The duration of action is 4-6 hours. Children have been observed to have faster and more extensive absorption, faster clearance, and a shorter half-life.
Caffeine is well absorbed after oral administration. The maximum concentration in blood plasma is reached after 15-45 minutes. It has been proven that caffeine improves the absorption of other components of the drug. Caffeine is rapidly distributed in body tissues, easily overcomes the placental and blood-brain barriers. About 17-36% of the dose binds to plasma proteins. The hepatic cytochrome P450 (CYP) isoenzyme 1A2 is involved in caffeine metabolism. In adults, the drug is rapidly metabolized in the liver to 1-methyluric acid and 7-methylxanthine. The half-life is about 3 hours. Caffeine and its metabolites are excreted by the kidneys; about 1% of the caffeine dose is excreted unchanged.
Indication
Symptomatic treatment of flu and cold symptoms (fever, headache, rhinitis, cough) in adults and children aged 12 years and over.
Contraindication
Hypersensitivity to paracetamol, caffeine, other xanthine derivatives (theophylline, theobromine) or to other components of the drug, especially parabens (methyl and propylparaben). Severe liver and kidney dysfunction (including hepatic and renal failure); congenital hyperbilirubinemia (including Gilbert, Dubin-Johnson, Rotor syndrome); glucose-6-phosphate dehydrogenase deficiency, rare hereditary forms of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltase deficiency. Alcoholism. Hematopoietic disorders, blood diseases, severe anemia, leukopenia, thrombosis, thrombophlebitis. States of increased excitement, sleep disorders. Severe cardiovascular diseases. Severe arterial hypertension, severe increase in blood pressure, organic diseases of the cardiovascular system (including atherosclerosis); decompensated heart failure; Cardiac conduction disorders; paroxysmal tachycardia, arrhythmia; tendency to vasospasm; ischemic heart disease, acute myocardial infarction. Glaucoma, including angle-closure glaucoma. Acute pancreatitis. Prostatic hypertrophy. Pheochromocytoma. Bladder neck obstruction. Diabetes mellitus. Epilepsy. Hyperthyroidism. Pyloroduodenal obstruction, gastric and duodenal ulcer in the acute stage, stenosing gastric ulcer, stenosing duodenal ulcer, acute pancreatitis and hepatitis. Bronchial asthma, chronic obstructive pulmonary disease. Risk of respiratory failure. Age over 60 years. Children up to 12 years. Pregnancy and breastfeeding.
Do not use with monoamine oxidase inhibitors (MAOIs) and within 2 weeks of discontinuing MAOIs.
Contraindicated in patients taking tricyclic antidepressants or beta-blockers.
Do not use in patients with phenylketonuria. It is not recommended for use in patients with increased blood clotting, a tendency to thrombus formation.
Do not use with medications that suppress or increase appetite and amphetamine-like psychostimulants.
Interaction with other medicinal products and other types of interactions
The simultaneous use of the drug Gripout, tablets, with monoamine oxidase inhibitors (MAO), tricyclic antidepressants, methyldopa is contraindicated due to the possible occurrence of severe arterial hypertension, tachycardia, hyperthermia, and dysfunction of vital organs, which can lead to death.
When used simultaneously with paracetamol, the following interactions may occur: slowing down the elimination of antibiotics from the body; tetracycline increases the risk of developing anemia and methemoglobinemia caused by paracetamol; antacids and food reduce the absorption of paracetamol. Metoclopramide and domperidone accelerate the absorption of paracetamol, and cholestyramine reduces the rate of its absorption. Probenecid affects the concentration of paracetamol in the blood plasma and its excretion. Simultaneous use of barbiturates, tricyclic antidepressants, as well as alcohol consumption is contraindicated.
Barbiturates reduce the antipyretic effect of paracetamol. When paracetamol is used simultaneously with hepatotoxic drugs, the toxic effect of the drug on the liver increases. Simultaneous use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome. It is not recommended to use it simultaneously with vasoconstrictor drugs.
The drug enhances the effect of indirect anticoagulants (warfarin, coumarin derivatives), which increases the risk of bleeding with simultaneous long-term regular daily use of paracetamol. With short-term use according to the recommended regimen, these interactions are not clinically significant.
Anticonvulsants (including phenytoin, barbiturates, carbamazepine), which stimulate the activity of liver microsomal enzymes, may enhance the toxic effect of paracetamol on the liver due to an increase in the degree of conversion of the drug to hepatotoxic metabolites. With simultaneous use, paracetamol enhances the hepatotoxicity of chloramphenicol.
Long-term use of anticonvulsants may reduce the activity of paracetamol.
Concomitant use of paracetamol with azidothymidine may cause the development of neutropenia.
Paracetamol reduces the effectiveness of diuretics.
The use of phenylephrine hydrochloride with indomethacin and bromocriptine can cause severe arterial hypertension. Rauwolfia alkaloids reduce the therapeutic effect of phenylephrine hydrochloride. α-blockers (phentolamine), phenothiazines, furosemide and other diuretics prevent vasoconstriction. Tachycardia may occur with simultaneous use of phenylephrine hydrochloride with atropine. The drug reduces the hypotensive effect of guanethidine, which, in turn, increases the alpha-adrenostimulating activity of phenylephrine.
Antidepressants, antiparkinsonian and antipsychotic drugs, phenothiazine derivatives increase the risk of urinary retention, dry mouth, constipation. Simultaneous use with ergot alkaloids (ergotamine, methysergide) increases the risk of ergotism, with haloman – increases the risk of ventricular arrhythmia.
The depressant effect of chlorpheniramine maleate can be significantly increased by simultaneous use with hypnotics, barbiturates, sedatives, neuroleptics, tranquilizers, anesthetics, narcotic analgesics, ethanol-containing drugs. Like other antihistamines, chlorpheniramine maleate enhances the sedative effect caused by central nervous system (CNS) depressants when used simultaneously, enhances the anticholinergic effect of atropine, antispasmodics, tricyclic antidepressants, antiparkinsonian drugs and drugs that depress the central nervous system (tranquilizers, barbiturates). Tricyclic antidepressants enhance the sympathomimetic effect of the drug. Chlorpheniramine, when used simultaneously with MAO inhibitors, can lead to hypertensive crisis, nervous
agitation, hyperpyrexia. The drug is not recommended for patients who are taking monoamine oxidase inhibitors or have completed therapy with them less than two weeks ago.
In the case of the use of maprotiline (a tetracyclic antidepressant) and other drugs with anticholinergic action, the anticholinergic effect of these drugs or of antihistamines such as chlorpheniramine may be enhanced.
Chlorpheniramine maleate inhibits the metabolism of phenytoin and increases its toxicity.
Glucocorticosteroids when used simultaneously with chlorpheniramine maleate increase the risk of developing glaucoma.
Incompatibility of chlorpheniramine maleate with calcium chloride, kanamycin sulfate, noradrenaline, and phenobarbital has been noted.
Do not use simultaneously with alcohol. Chlorpheniramine maleate and alcohol potentiate each other's effects.
Caffeine enhances the effect (improves bioavailability) of analgesics-antipyretics, potentiates the effects of xanthine derivatives, α- and β-adrenomimetics, and psychostimulants.
Caffeine increases the likelihood of liver damage from hepatotoxic drugs.
Cimetidine, hormonal contraceptives, isoniazid enhance the effect of caffeine. Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics and sedatives, is an antagonist of anesthetics and other drugs that depress the central nervous system, a competitive antagonist of adenosine drugs, ATP. With simultaneous use of caffeine with ergotamine, the absorption of ergotamine in the gastrointestinal tract improves, with thyroid-stimulating drugs - the thyroid effect increases. Caffeine reduces the concentration of lithium in the blood.
Application features
Do not exceed the indicated doses.
Use with caution in individuals prone to high blood pressure.
It is necessary to consult a doctor regarding the possibility of using the drug in patients with impaired kidney and liver function.
Patients with difficulty urinating or Raynaud's disease (which can cause pain in the fingers and toes in response to cold or stress) should consult a doctor before using the drug.
Concomitant use with other drugs intended for the symptomatic treatment of colds and flu, drugs containing paracetamol, sympathomimetics (phenylephrine, pseudoephedrine), barbiturates, tranquilizers should be avoided, since their simultaneous use with paracetamol may cause liver dysfunction.
If symptoms persist, consult a doctor. If headache becomes persistent, consult a doctor. This medicine is not recommended for use with sedatives, hypnotics.
If, on the recommendation of a doctor, the drug is used for a long period, it is necessary to monitor the functional state of the liver and the picture of peripheral blood. With prolonged use in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia are possible.
The risk of overdose is increased in alcoholic liver disease. This medicine is not recommended for use simultaneously with beverages containing alcohol.
It should be noted that patients with alcoholic non-cirrhotic liver damage have an increased risk of hepatotoxic effects of paracetamol.
When using the drug, you should avoid excessive consumption of coffee, strong tea, other tonic drinks and medications containing caffeine. This may cause sleep problems, tremors, tension, irritability, and palpitations.
Patients with severe infections such as sepsis, which are accompanied by a decrease in glutathione levels, are at increased risk of metabolic acidosis when taking paracetamol. Symptoms of metabolic acidosis include deep, rapid or difficult breathing, nausea, vomiting, loss of appetite. You should seek immediate medical attention if these symptoms occur.
Use with caution in compensated heart failure, patients at risk of seizures, patients with obstructive airway diseases, persistent or chronic cough resulting from smoking or emphysema, when cough is accompanied by excessive sputum secretion, patients with congenitally prolonged QT interval or in cases of prolonged use of drugs that may prolong the QT interval.
Phenylephrine, which is part of the drug, can cause angina attacks.
The drug may affect the results of laboratory tests for blood glucose and uric acid. The use of the drug may cause a positive analytical result in doping control. Before using the drug, it is necessary to consult a doctor, patients who use warfarin or similar drugs with anticoagulant effect, and patients with impaired kidney and liver function.
The drug contains lactose, so it should not be used in patients with hereditary galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Keep the drug out of the sight and reach of children.
Excipients methylparaben (E 218), propylparaben (E 216) may cause allergic reactions (possibly delayed), and in some cases - bronchospasm.
If the signs of the disease do not disappear within 3 days of treatment with the drug or, conversely, the state of health worsens, you should consult a doctor.
Ability to influence reaction speed when driving vehicles or other mechanisms
Given the possibility of decreased psychomotor reactions, as well as the occurrence of reactions from the nervous system and organs of vision, it is not recommended to drive vehicles and mechanisms during treatment.
Use during pregnancy or breastfeeding
The drug is contraindicated during pregnancy. Breastfeeding should be discontinued during treatment with the drug. There are no data on the effect of the drug on fertility.
Method of administration and doses
Adults and children over 12 years of age should take 1 tablet 3-4 times a day. The interval between doses should be at least 4 hours. The drug should be taken at least half an hour after meals.
The daily dose should not exceed 4 tablets.
The duration of treatment is determined by the doctor.
The maximum period of use without consulting a doctor is 3 days.
Children
Contraindicated for children under 12 years of age.
Overdose
Paracetamol overdose can cause liver failure. Liver damage is possible in adults who have taken more than 10 g, and in children who have taken more than 150 mg/kg of body weight, can lead to hepatocellular necrosis and the development of encephalopathy with impaired consciousness, hemorrhages, hypoglycemia, hypoglycemic coma, hepatic coma, cerebral edema, and in some cases - to death.
Symptoms of paracetamol overdose in the first 24 hours: increased sweating, psychomotor agitation or depression of the central nervous system, headache, pallor, dizziness, sleep disturbances, drowsiness, insomnia, general weakness, heart rhythm disturbances, tachycardia, reflex bradycardia, extrasystole, tremor, hyperreflexia, nausea, vomiting, irritability, restlessness, anorexia and abdominal pain. The activity of hepatic transaminases increases, the concentration of bilirubin increases and the level of prothrombin decreases. In severe cases, impaired consciousness, disorientation, hallucinations, convulsions and arrhythmias may occur. Signs of liver damage may appear 12–72 hours after overdose. Glucose metabolism disorders and metabolic acidosis may occur. In acute overdose, liver damage may result in toxic encephalopathy with impaired consciousness, coma and death. Pancreatitis and arrhythmia have been reported.
Acute renal failure with acute tubular necrosis may present with severe lumbar pain, hematuria, proteinuria, nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis, acute renal failure) and may develop even in the absence of severe liver damage.
With prolonged use in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia are possible.
It is believed that the additional amount of toxic metabolites in overdose irreversibly binds to liver tissues.
Overdose due to the action of phenylephrine may cause increased sweating, psychomotor agitation or depression of the central nervous system, headache, dizziness, insomnia, drowsiness, restlessness, impaired consciousness, behavioral changes, delirium, cardiac arrhythmias, tachycardia, extrasystole, arrhythmia, tremor, hyperreflexia, convulsions, nausea, vomiting, irritability, anxiety, increased blood pressure.
In case of an overdose of chlorpheniramine maleate, the state can vary from depressed (sedation, apnea, collapse) to excited (insomnia, hallucinations, restlessness, tremors and convulsions). Additionally observed: dizziness, tinnitus, ataxia, decreased visual acuity and arterial hypotension. Atropine-like symptoms may be observed, including mydriasis, photophobia, dry skin and mucous membranes, increased body temperature, intestinal atony. CNS depression is accompanied by respiratory disorders and disorders of the cardiovascular system (decreased pulse rate, decreased blood pressure up to vascular insufficiency).
In case of caffeine overdose, the following symptoms are observed: dehydration, hyperthermia, tinnitus, epigastric pain, increased frequency of diuresis, extrasystole, tachycardia, rapid breathing, arrhythmia, effects on the central nervous system (dizziness, insomnia, excitement, irritability, psychomotor agitation, state of affect, anxiety, tremor, vomiting, seizures, convulsions, agitation, restlessness, delirium, increased tactile or pain sensitivity).
Treatment of overdose: In case of suspected overdose, the patient should be taken to hospital. Intravenous acetylcysteine is administered within 24 hours after paracetamol ingestion, with the maximum effect being achieved within the first 8 hours after ingestion. Oral methionine may be administered within the first 8 hours after overdose.
Adverse reactions
Skin and subcutaneous tissue disorders: skin and mucous membrane rashes (usually erythematous), itching, urticaria, purpura, allergic and angioedema, acute generalized exanthematous pustulosis, local drug dermatitis, erythroderma, erythema multiforme, exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), hemorrhages, photosensitization, including fatal outcomes.
Immune system disorders: hypersensitivity reactions (including angioedema), anaphylaxis, anaphylactic shock.
On the part of the psyche: psychomotor agitation, nervous agitation, impaired attention and orientation, anxiety, change in behavior, euphoria, anxiety, feeling of fear, irritability, sleep disturbances, insomnia, drowsiness, night terrors, confusion, depressive states, hallucinations, anxiety, increased fatigue, sedation.
Neurological disorders: headache, dizziness, muscle weakness, dyskinesia, tremor, paresthesia, tingling and heaviness in the extremities, convulsions, epileptic seizures, in rare cases - coma.
From the side of the organs of hearing and vestibular apparatus: tinnitus, vertigo.
On the part of the organs of vision: impaired vision and accommodation, mydriasis, increased intraocular pressure, development of glaucoma (angle-closure glaucoma), dry eyes.
Gastrointestinal: nausea, vomiting, diarrhea, constipation, flatulence, dry mouth, oral mucosal ulcers, hypersalivation, abdominal discomfort and pain, heartburn, exacerbation of peptic ulcer disease, decreased appetite, hemorrhages, heartburn, diarrhea.
Metabolic disorders: zinc and copper metabolism disorders.
From the hepatobiliary system: impaired liver function, increased activity of liver enzymes, hepatotoxicity, hepatonecrosis (dose-dependent effect), liver failure, hepatitis, jaundice.
On the part of the endocrine system: hypoglycemia, up to hypoglycemic coma; hyperglycemia.
On the part of the kidneys and urinary system: urination disorders, urinary retention (more likely in patients with prostatic hypertrophy), urinary retention and dysuria, difficulty urinating, aseptic pyuria, oliguria, glycosuria, renal colic, interstitial nephritis, papillary necrosis, nephrotoxic effect, increased creatinine clearance, increased sodium and calcium excretion.
From the blood and lymphatic system: bruising, bleeding, anemia, sulfhemoglobinemia and methemoglobinemia, hemolytic anemia, aplastic anemia, erythrocytopenia, thrombocytopenia, hyperprothrombinemia, leukopenia, neutropenia, pancytopenia, agranulocytosis.
From the cardiovascular system: increased blood pressure (mainly in patients with arterial hypertension), tachycardia or reflex bradycardia, palpitations, shortness of breath, heart pain, arrhythmia, edema, myocardial dystrophy (dose-dependent effect with prolonged use).
Respiratory, thoracic and mediastinal disorders: bronchospasm in patients sensitive to aspirin and other nonsteroidal anti-inflammatory drugs; dry nose, cyanosis, shortness of breath.
With prolonged use in high doses: damage to the glomerular apparatus, kidneys, crystalluria, formation of urate, cystine and/or oxalate stones in the kidneys and urinary tract, renal failure, damage to the insular apparatus, pancreas (hyperglycemia, glucosuria) and impaired glycogen synthesis up to the onset of diabetes. Simultaneous administration of the drug in recommended doses with products containing caffeine may enhance side effects caused by caffeine, such as dizziness, increased excitability, insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disorders and rapid heartbeat.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
4 tablets in a strip or blister; 1 strip or blister in a cardboard box No. 4 (4x1).
Vacation category
Without a prescription - No. 4 (4x1), No. 10 (10x1).
Producer
Marksans Pharm LTD.
Location of the manufacturer and its business address
L-56/57, Phase II-D, Verna Industrial Estate, Verna, Salsette, Goa - 403 722, India.
