Instructions for Coldflu tablets No. 200
Composition
active ingredients: paracetamol, caffeine, phenylpropanolamine hydrochloride, chlorpheniramine maleate; 1 tablet contains: paracetamol 500 mg, caffeine 30 mg, phenylpropanolamine hydrochloride 25 mg, chlorpheniramine maleate 2 mg;
excipients: microcrystalline cellulose, corn starch, titanium dioxide (E 171), povidone, sodium methylhydroxybenzoate (E 217), sodium propylhydroxybenzoate (E 219), magnesium stearate, sodium starch glycolate, Ponceau 4R lake dye (E 124).
Dosage form
Pills.
Main physicochemical properties: pink tablets, with specks, flat, round, with beveled edges, with a score line on one side and smooth on the other side.
Pharmacotherapeutic group
Analgesics and antipyretics.
ATX code N02B.
Pharmacological properties
The effect of the drug depends on the action of individual components.
Pharmacodynamics.
A combination drug for the treatment of flu and cold symptoms.
It has antipyretic, decongestant, analgesic and antiallergic effects. Paracetamol has analgesic, antipyretic and mild anti-inflammatory effects by inhibiting prostaglandin synthesis in the central nervous system (CNS). It reduces the excitation of the thermoregulation center in the hypothalamus.
Chlorpheniramine maleate is a histamine receptor blocker that inhibits the biological effects of histamine. It has an antiallergic effect, helps reduce the manifestations of local exudative reactions of the nasal mucosa and paranasal sinuses. It suppresses the symptoms of rhinitis, rhinorrhea, stinging in the eyes, unpleasant sensations in the nasopharynx and larynx.
Phenylpropanolamine hydrochloride is an adrenomimetic. Due to its vasoconstrictor effect, and
Also, due to direct stimulation of α-adrenergic receptors of the blood vessels of the nasal mucosa, it reduces the phenomena of nasal hyperemia, edema, and improves airway patency.
The mechanism of action of caffeine is due to the inhibition of the enzyme phosphodiesterase, which leads to intracellular accumulation of cAMP. The latter enhances glycogenolysis, stimulates metabolism in organs and tissues, including the CNS and muscles. Caffeine enhances and regulates the processes of excitation in the cerebral cortex. The neurochemical mechanism of the stimulating effect of caffeine lies in its ability to block specific P1 "purine" (or adenosine) receptors in the brain, the endogenous ligand of which is adenosine, which reduces the processes of excitation in the brain. Caffeine stimulates the CNS, increases mental and
physical activity, reduces the feeling of fatigue, increases the strength and frequency of heart contractions.
Caffeine stimulates the respiratory and vasomotor centers, increases the tone of the cerebral vessels, dilates the vessels of skeletal muscles, heart, and kidneys, and reduces platelet aggregation.
Coldflu provides a therapeutic effect within 12 hours after administration.
Pharmacokinetics.
After oral administration, paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 10–60 minutes.
Paracetamol is distributed in most body tissues. It crosses the placental barrier and is excreted in breast milk. At usual therapeutic doses, paracetamol binds to plasma proteins to a negligible extent, but the degree of binding increases with increasing concentration.
Paracetamol is mainly metabolized in the liver by two pathways: glucuronidation and sulfation. It is excreted in the urine, mainly as glucuronide and sulfate conjugates. The half-life is 1 to 3 hours.
Caffeine is well absorbed from the digestive system. It is evenly distributed in the body. It easily penetrates the blood-brain barrier. Biotransformation: demethylation and oxidation. It is excreted in the urine as metabolites, about 8% in an unchanged state. The half-life is 3.9–5.3 hours, completely excreted after 24 hours.
Phenylpropanolamine hydrochloride is rapidly and completely absorbed from the gastrointestinal tract (GI). Maximum plasma concentration is reached after 1–2 hours. It is not subject to presystemic metabolism, so bioavailability is about 100%. The half-life is 3–5 hours. About 90–100% is excreted unchanged in the urine within 24 hours after administration.
Chlorpheniramine maleate is well absorbed from the gastrointestinal tract, its action begins 30 minutes after administration and lasts for 3–6 hours. It is metabolized during the “first pass” through the liver and, possibly, intrahepatic recirculation. Taking chlorpheniramine with food significantly reduces its bioavailability. A small amount of the drug is excreted unchanged in the urine. Most of it is excreted from the body in the form of metabolic products.
Indication
Symptomatic treatment of acute respiratory viral infections (ARVI) and influenza, which are accompanied by fever, chills, headache, runny nose and nasal congestion, sneezing, aches and pains in the body.
Contraindication
Hypersensitivity to any of the components of the drug. Severe cardiovascular diseases, severe liver and/or kidney dysfunction, congenital hyperbilirubinemia, arterial hypertension, acute pancreatitis, hyperthyroidism, pheochromocytoma, blood diseases (including severe anemia, leukopenia), thrombosis, thrombophlebitis, angle-closure glaucoma, glucose-6-phosphate dehydrogenase deficiency, severe forms of diabetes mellitus, alcoholism, prostatic hypertrophy with urinary retention, bladder neck obstruction, pyloroduodenal obstruction, bronchial asthma, epilepsy, sleep disorders.
Increased excitability. Sleep disturbances. Epilepsy. Use simultaneously with monoamine oxidase inhibitors (MAO) and within 2 weeks after discontinuation of their use.
Hypersensitivity to bromocriptine or other ergot alkaloids, severe gastrointestinal diseases, mental disorders.
Concomitant use with tricyclic antidepressants, β-blockers or other antihypertensive drugs and sympathomimetics.
Elderly patient (60 years and older). Pregnancy or breastfeeding. Children under 12 years of age.
It is not recommended for use in patients with increased blood clotting or 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 drug interactions that each individual component of Coldflu may involve are well known. There is no reason to assume that the use of these ingredients in combination would affect the drug interaction profile.
Paracetamol
With regular long-term use of paracetamol, the anticoagulant effect of warfarin or other coumarin derivatives may be enhanced, as well as the risk of bleeding may increase. With occasional use of paracetamol, this effect is not pronounced.
Hepatotoxic drugs may increase the likelihood of paracetamol accumulation and overdose. The risk of developing hepatotoxic effects of paracetamol may increase in patients receiving drugs that induce liver microsomal enzymes, such as barbiturates and antiepileptic drugs (phenytoin, phenobarbital, carbamazepine), and the antituberculosis drugs rifampicin and isoniazid.
Metoclopramide increases the rate of absorption of paracetamol and leads to an increase in its maximum plasma levels. Similarly, domperidone may increase the rate of absorption of paracetamol. Paracetamol may prolong the half-life of chloramphenicol.
Paracetamol may reduce the bioavailability of lamotrigine with a possible reduction in its effect due to possible induction of its metabolism in the liver.
The absorption of paracetamol may be reduced when co-administered with cholestyramine, but the reduction in absorption is insignificant if cholestyramine is administered 1 hour later.
Regular use of paracetamol simultaneously with zidovudine may lead to the development of neutropenia and an increased risk of liver damage. Paracetamol reduces the effectiveness of diuretics.
Probenecid affects the metabolism of paracetamol. The dose of paracetamol should be reduced in patients taking probenecid concomitantly.
The hepatotoxicity of paracetamol may be increased by prolonged or excessive alcohol consumption. Paracetamol may interfere with the results of phosphotungstic acid tests.
Phenylpropanolamine
The interaction of phenylpropanolamine hydrochloride with MAO inhibitors causes a hypertensive effect, with tricyclic antidepressants (amitriptyline) - increases the risk of cardiovascular side effects, with digoxin and cardiac glycosides - leads to arrhythmias and myocardial infarction. Phenylpropanolamine when used with other sympathomimetics increases the risk of adverse cardiovascular reactions, may reduce the effectiveness of β-blockers and other antihypertensive drugs (reserpine, methyldopa) with an increased risk of arterial hypertension and adverse cardiovascular reactions.
Chlorpheniramine
Maprotiline (a tetracyclic antidepressant) and other anticholinergic drugs: the anticholinergic effect of these drugs or antihistamines such as chlorpheniramine may be enhanced. The use of chlorpheniramine simultaneously with MAO inhibitors, furazolidone may lead to hypertensive crisis, nervous excitement, hyperpyrexia. 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 halothane - increases the risk of ventricular arrhythmia.
The depressant effect of chlorpheniramine maleate can be significantly increased by simultaneous use of the drug with: hypnotics, barbiturates, sedatives, neuroleptics, tranquilizers, anesthetics, narcotic analgesics, alcohol. Chlorpheniramine maleate enhances the anticholinergic effect of atropine, antispasmodics, tricyclic antidepressants, antiparkinsonian drugs.
Incompatibility of chlorpheniramine maleate with calcium chloride, kanamycin sulfate, noradrenaline, and phenobarbital has been noted.
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 by hepatotoxic drugs.
Cimetidine, hormonal contraceptives, and isoniazid enhance the effects 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, adenosine-5'-triphosphate (ATP). When caffeine is used simultaneously with ergotamine, the absorption of ergotamine in the gastrointestinal tract improves, and with thyroid-stimulating drugs, the thyroid effect increases. Caffeine reduces the concentration of lithium in the blood. Simultaneous use of caffeine with MAO inhibitors can cause a dangerous increase in blood pressure.
Ototoxic and photosensitizing drugs when used simultaneously may increase side effects. Tricyclic antidepressants enhance sympathomimetic effects. Glucocorticosteroids increase the risk of glaucoma.
Application features
Concomitant use of other medicines containing paracetamol should be avoided due to the risk of severe liver damage in case of overdose.
The drug is not recommended for use simultaneously with vasoconstrictors. Do not exceed the indicated doses.
When using the drug, you should avoid drinking alcoholic beverages, since ethyl alcohol, when taken simultaneously with paracetamol, can cause liver dysfunction.
The drug should be used with caution in patients with mild to moderate renal and/or hepatic impairment, acute hepatitis, severe hemolytic anemia, chronic malnutrition and dehydration, mild to moderate cardiovascular disease, mild to moderate diabetes mellitus, prostatic hypertrophy without urinary retention, as patients may be predisposed to developing urinary retention, patients with stenosing peptic ulcer, Raynaud's disease, thyroid disease (except hyperthyroidism), chronic lung disease, as well as patients taking medications that affect the liver, and the elderly.
Serious skin reactions, such as acute generalised exanthematous pustulosis, Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported very rarely in patients taking paracetamol. The drug should be discontinued if skin rash or other signs of hypersensitivity appear.
Taking the drug in doses that exceed the recommended ones may lead to liver damage.
Chlorpheniramine may mask symptoms of hypersensitivity and affect the results of skin tests.
The drug should be prescribed only by a doctor after assessing the risk/benefit ratio in the following cases: arterial hypertension; moderate heart disease; heart rhythm disorders; liver disease; urination disorders. 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 peripheral blood picture.
Patients should consult a doctor:
if they have breathing problems such as asthma, emphysema, or chronic bronchitis;
if symptoms do not improve within 5 days or if symptoms are accompanied by a high fever lasting more than 3 days, rash, or persistent headache;
regarding the possibility of using the drug in cases of impaired kidney and liver function.
These symptoms may be symptoms of a more serious condition.
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, palpitations, dizziness, arrhythmia.
If the high fever persists for 3 days or more or increases again, and the pain does not stop within 5 days, it is necessary to review the treatment tactics.
Before using the drug, it is necessary to consult a doctor if the patient is using warfarin or similar drugs that have an anticoagulant effect, as well as in patients with difficulty urinating, Raynaud's disease (which can manifest as pain in the fingers and toes in response to cold or stress).
It is necessary to consult a doctor regarding the possibility of using the drug in patients with impaired kidney and liver function.
It should be taken into account that patients with alcoholic liver disease are at increased risk of hepatotoxic effects of paracetamol. The drug may affect the results of laboratory tests for blood glucose and uric acid.
Patients who take analgesics every day for mild arthritis should consult a doctor.
If the symptoms of the disease do not disappear within 3 days, you should consult a doctor.
Severe skin reactions have been reported very rarely. If you experience redness, rash, blistering or peeling of the skin, discontinue use and seek immediate medical attention.
Excipients
The dye "Ponso 4R" (E 124), which is part of the tablet, may cause allergic reactions.
Sodium methylparaben (E 219) and sodium propylparaben (E 216), which are part of the tablet, may cause allergic reactions (possibly delayed).
Use during pregnancy or breastfeeding
The drug is contraindicated in women during pregnancy or breastfeeding.
The ability to influence the reaction speed when driving or working with other mechanisms
While using the drug, you should refrain from driving vehicles and performing work that requires increased attention and speed of psychomotor reactions.
Method of administration and doses
Coldflu should be taken orally. The tablet should be taken with plenty of water.
Adults and children over 12 years of age should take 1 tablet every 6 hours, but not more than 4 tablets per day. The duration of treatment is determined by the doctor. The maximum period of use without consulting a doctor is 3 days.
Do not exceed the recommended dose.
Patients with liver failure.
For patients with impaired liver function or Gilbert's syndrome, the dose should be reduced or the interval between doses should be increased.
Elderly patients: No dose adjustment is required for elderly patients.
Children
The use of the drug is contraindicated in children under 12 years of age.
Overdose
In the event of an overdose of the drug, the symptoms caused by an overdose of paracetamol will be the most pronounced.
Symptoms caused by paracetamol overdose: hepatotoxic effect, in severe cases liver necrosis develops. Paracetamol overdose, including high total doses received over a long period, can cause analgesic-induced nephropathy with irreversible liver dysfunction.
Liver damage is possible in adults who have taken 10 g or more of paracetamol, and in children who have taken more than 150 mg/kg of body weight. In patients with risk factors: regular excessive use of ethanol, glutathione cachexia (digestive disorders, cystic fibrosis, HIV infection, cachexia), the use of 5 g or more of paracetamol can lead to liver damage.
There is a risk of poisoning, especially in elderly patients, young children, patients with liver disease, patients with chronic malnutrition and patients receiving inducers of liver enzymes (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort). In severe poisoning, liver failure may progress to encephalopathy, coma and death.
With prolonged use of the drug in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia may develop from the hematopoietic system. When taking large doses, from the central nervous system - dizziness, psychomotor agitation and disorientation; from the urinary system - nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).
Symptoms of paracetamol overdose, which appear in the first 24 hours: pallor, nausea, vomiting and lack of appetite. The first sign of liver damage may be abdominal pain, which does not always appear in the first 24-48 hours, but may occur later, during a period of up to 4-6 days after taking the drug. Liver damage usually occurs a maximum of 72-96 hours after taking the drug. Abnormalities in glucose metabolism (hypoglycemia) and metabolic acidosis, hemorrhages may be observed. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage and manifest as severe back pain, hematuria, proteinuria. Cases of cardiac arrhythmias and pancreatitis have been reported.
Overdose of phenylpropanolamine hydrochloride causes hyperhidrosis, psychomotor agitation or CNS depression, insomnia, behavioral changes, headache, dizziness, drowsiness, impaired consciousness, tachycardia, arrhythmias, extrasystole, tremor, hyperreflexia, convulsions, nausea, vomiting, irritability, anxiety, and arterial hypertension.
In case of an overdose of chlorpheniramine maleate, the condition may vary from depressed to excited (restlessness and convulsions). Atropine-like symptoms may be observed: mydriasis, photophobia, dry skin and mucous membranes, increased body temperature, intestinal atony, decreased level of consciousness, increased temperature, urinary retention, tachycardia, nausea, vomiting, excited state, hallucinations, mental disorders, seizure or arrhythmia. CNS depression is accompanied by respiratory disorders and cardiovascular disorders (decreased pulse rate, decreased blood pressure up to vascular failure). Rhabdomyolysis and renal failure may rarely develop in patients with prolonged agitation, convulsions or in patients in coma.
Symptoms of caffeine overdose. Large doses of caffeine can cause epigastric pain, vomiting, diuresis, rapid breathing, extrasystole, tachycardia or cardiac arrhythmia, hypertension with subsequent hypotension, supraventricular and ventricular arrhythmias, central nervous system manifestations (dizziness, insomnia, nervous excitement, irritability, affective state, anxiety, tremor, convulsions, agitation, restlessness, delirium, increased tactile or pain sensitivity), headache, chills, hot flashes, delusions, rigidity, altered consciousness, loss of appetite, weakness, fever, hallucinations, hypokalemia, hyponatremia, increased blood sugar, metabolic acidosis, acute necrosis of skeletal muscles. Clinically important symptoms of caffeine overdose are also associated with paracetamol liver damage.
There is no specific antidote for caffeine, but supportive measures, such as the use of β-adrenergic antagonists, may alleviate the cardiotoxic effect. Gastric lavage is necessary, oxygen therapy is recommended, and diazepam is recommended for convulsions. Symptomatic therapy.
Within the first 6 hours after a suspected overdose, gastric lavage should be performed with subsequent hospitalization of the patient.
During the first 8 hours after overdose – use of methionine orally or intravenous administration of cysteamine or N-acetylcysteine; symptomatic therapy; in severe hypertension – use of α-, β-adrenergic blockers, monitoring of the respiratory and circulatory systems (adrenaline cannot be used).
Side effects
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: anaphylaxis; hypersensitivity reactions including pruritus, skin and mucous membrane rashes (usually generalized and erythematous rash, urticaria); erythema multiforme exudative (including Stevens-Johnson syndrome), anaphylactic shock, angioedema, toxic epidermal necrolysis (Lyell's syndrome), hypersensitivity necrotizing angiitis, facial edema, eyelid edema, tongue edema, hand edema.
From the nervous system: headache, dizziness, psychomotor agitation and disorientation, anxiety, nervous excitement, feeling of fear, irritability, sleep disturbances, insomnia, drowsiness, confusion, hallucinations, nightmares, depressive states, euphoria, difficulty breathing, tremor, tingling and heaviness in the limbs, feeling of discomfort, tinnitus, epileptic seizures, anxiety, in some cases - coma, convulsions, dyskinesia, behavioral changes, general weakness.
On the part of the respiratory system: bronchospasm in patients sensitive to acetylsalicylic (aspirin) acid and other nonsteroidal anti-inflammatory drugs, dry nose, cyanosis, shortness of breath.
On the part of the organs of vision: impaired vision and accommodation, mydriasis, increased intraocular pressure, dry eyes.
From the side of the organs of hearing and vestibular apparatus: tinnitus, vertigo.
Gastrointestinal: nausea, vomiting, heartburn, dry mouth, sore mouth, hoarseness, discomfort and pain in the epigastric region, diarrhea, hemorrhages, constipation, flatulence, hypersalivation, decreased appetite, exacerbation of peptic ulcer.
On the part of the hepatobiliary system: impaired liver function, increased activity of liver enzymes, usually without the development of jaundice; hepatotoxic effect, hepatonecrosis (when using high doses).
On the part of the endocrine system: hypoglycemia, up to hyperglycemic coma.
On the part of the kidneys and urinary system: nephrotoxicity, interstitial nephritis, papillary necrosis, urination disorders, dysuria, increased excretion of sodium and calcium, urinary retention and difficulty urinating, aseptic pyuria, renal colic, nephrotoxic effect, oliguria.
From the cardiovascular system: arterial hypertension, tachycardia or reflex bradycardia, arrhythmia, shortness of breath, pain in the heart area, palpitations, edema, myocardial dystrophy (dose-dependent effect with prolonged use).
Others: general weakness, increased sweating, fever, hypoglycemia, glycosuria, impaired zinc and copper metabolism, increased creatinine clearance, increased sodium and calcium excretion, nasal congestion; possible false increase in uric acid in the blood, determined by the Bittner method; slight increase in 5-hydroxyindoleacetic acid, vanillylmandelic acid and catecholamines in the 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, 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
4 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
4 tablets in a strip; 1 strip in a cardboard envelope; 50 envelopes in a cardboard box.
Vacation category
According to the recipe.
Producer
Genom Biotech Pvt. Ltd.
Address
Plot No. D-121, 122, 123, M.I.D.C. Malegaon, Tal. Sinnar, Nashik 422103, Maharashtra, India.
