Instructions Gripout tablets strip No. 10
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 exhibits a vasoconstrictor effect, mainly in relation to 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 binds 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 blood plasma proteins. The hepatic cytochrome P450 (CYP) isoenzyme 1A2 is involved in the metabolism of caffeine. 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 propyl parahydroxybenzoate). Severe liver and kidney dysfunction (including hepatic and renal failure); congenital hyperbilirubinemia (including Gilbert's, Dubin-Johnson, Rotor syndrome); glucose-6-phosphate dehydrogenase deficiency, rare hereditary forms of fructose intolerance, glucose-galactose malabsorption or sucrose-isomaltose insufficiency.
Severe cardiovascular diseases. Severe arterial hypertension, pronounced 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 ulcers in the acute stage, stenosing gastric ulcers, stenosing duodenal ulcers, acute pancreatitis and hepatitis. Bronchial asthma, chronic obstructive pulmonary disease. Patients at risk of respiratory failure.
Age over 60 years. Children under 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.
Special safety measures.
Do not exceed the specified dose.
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, as they may cause liver dysfunction when taken simultaneously with paracetamol.
If symptoms persist, consult a doctor. If headache becomes persistent, consult a doctor. This medicine is not recommended for use simultaneously 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 who take analgesics every day for mild arthritis should consult a doctor.
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, you should consult a doctor if you are using warfarin or similar drugs that have an anticoagulant effect and in 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.
Interaction with other medicinal products and other types of interactions
The simultaneous use of the drug Gripout tablets with monoamine oxidase inhibitors (MAOIs), 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 types of interactions may be observed: the elimination of antibiotics from the body may be slowed down; 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. With the simultaneous use of barbiturates, tricyclic antidepressants, as well as alcohol, an increase in the half-life of paracetamol is possible.
Do not use simultaneously with alcohol and tricyclic antidepressants.
Barbiturates reduce the antipyretic effect of paracetamol.
The drug enhances the effect of indirect anticoagulants (warfarin, coumarin derivatives), which may increase 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.
With simultaneous use of paracetamol 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.
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 interaction of phenylephrine hydrochloride with MAO inhibitors causes a hypertensive effect, with tricyclic antidepressants (amitriptyline) - increases the risk of cardiovascular side effects, with sympathomimetic amines, digoxin and cardiac glycosides - increases the risk of arrhythmias and myocardial infarction. Phenylephrine with other sympathomimetics increases the risk of adverse cardiovascular reactions, increases arrhythmogenicity, may reduce the effectiveness of β-blockers and other antihypertensive drugs (reserpine, methyldopa) with an increased risk of arterial hypertension and adverse cardiovascular reactions. The use of phenylephrine hydrochloride with indomethacin and bromocriptine may cause severe arterial hypertension. Rauwolfia alkaloids reduce the therapeutic effect of phenylephrine hydrochloride. α-adrenergic blockers (phentolamine), phenothiazines, furosemide and other diuretics prevent vasoconstriction. Tachycardia may occur when phenylephrine hydrochloride is used simultaneously with atropine. The drug reduces the hypotensive effect of guanethidine, which, in turn, increases the alpha-adrenostimulating activity of phenylephrine.
The simultaneous use of the drug with hypnotics, barbiturates, sedatives, neuroleptics, tranquilizers, anesthetics, narcotic analgesics, ethanol-containing drugs can significantly increase the inhibitory effect of chlorpheniramine maleate. Like other antihistamines, chlorpheniramine maleate enhances the sedative effect caused by central nervous system 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 simultaneously with MAO inhibitors can lead to hypertensive crisis, nervous excitement, hyperpyrexia. The drug is not recommended for use in patients who are taking monoamine oxidase inhibitors or have completed therapy with them less than two weeks ago.
Maprotiline (a tetracyclic antidepressant) and other anticholinergic drugs: the anticholinergic effect of these drugs or 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, when used simultaneously with alcohol, potentiates the effects of each other.
Caffeine enhances the effect (improves bioavailability) of analgesics-antipyretics, potentiates the effects of xanthine derivatives, α- and β-adrenomimetics, and psychostimulants.
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.
Use during pregnancy and breastfeeding
The drug is contraindicated during pregnancy. Breastfeeding should be discontinued during treatment with the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
During treatment, it is not recommended to drive vehicles and operate machinery.
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 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 body weight,
can lead to hepatocellular necrosis with the development of encephalopathy with impaired consciousness, hemorrhages, hypoglycemia, hypoglycemic coma, hepatic coma, cerebral edema, and in some cases, fatal outcome.
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.
Ingestion of 5 g or more of paracetamol may cause liver damage in patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort or other drugs that induce liver enzymes; regular intake of excessive amounts of ethanol; glutathione cachexia (digestive disorders, cystic fibrosis, HIV infection, starvation, cachexia).
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).
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 dermatitis, erythroderma, erythema multiforme, exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), hemorrhages, photosensitization.
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, weakness, 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, 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.
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; nasal dryness, cyanosis, shortness of breath.
Others: general weakness, fever, increased sweating, nasal congestion, possible false increase in blood uric acid, determined by the Bittner method; slight increase in 5-hydroxyindoleacetic acid (5-NIAA), vanillylmandelic acid (VMA) and catecholamines in urine.
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, damage to the insular apparatus, pancreas (hyperglycemia, glucosuria) and impaired glycogen synthesis up to the onset of diabetes mellitus.
Excipients methylparaben (E 218), propylparaben (E 216) may cause allergic reactions (possibly delayed) and in some cases bronchospasm.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.
Packaging
4 or 10 tablets in a strip; 1 strip in a cardboard box.
Vacation category
Without a prescription.
Producer
FDS Limited.
Location of the manufacturer and its business address
L-56/57, Phase II-D, Verna Industrial Estate, Verna, Salsette, Goa - 403 722, India
