Flucold®-n

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT FLUCOLD®-N (FLUCOLD®-N)

Composition:

Active substances: 1 tablet contains 500 mg of paracetamol, 30 mg of caffeine, 5 mg of phenylephrine hydrochloride, 2 mg of chlorpheniramine maleate;

Excipients: maize starch, sodium starch glycolate (type A), talc, gelatin, magnesium stearate, sorbitol solution (E 420), Povidone K-30, sodium benzoate (E 211), Ponceau 4R dye (E 124), purified water.

Pharmaceutical form. Tablets.

Main physicochemical properties: round, film-coating-free tablets of pink color with dark pink specks.

Pharmacotherapeutic group.

Analgesics and antipyretics. Paracetamol, combinations without psychotropic agents.

ATC code N02B E51.

Pharmacological Properties

Pharmacodynamics

The pharmacological activity of the drug is due to the properties of paracetamol, caffeine, phenylephrine hydrochloride, and chlorpheniramine maleate, which are components of the drug. Paracetamol exerts antipyretic, analgesic, and anti-inflammatory effects. The mechanism of action is associated with inhibition of prostaglandin synthesis.

Caffeine exerts a stimulating effect on the central nervous system, primarily on the cerebral cortex, respiratory and vasomotor centers, increases mental and physical performance, reduces drowsiness and fatigue, and attenuates the effects of agents that depress the central nervous system.

Phenylephrine hydrochloride exerts vasoconstrictive action, reduces swelling of the nasal mucosa and paranasal sinuses.

Chlorpheniramine maleate exerts antihistaminic and anticholinergic effects. By blocking H1-receptors, it produces an antiallergic effect, reduces vascular permeability of the mucous membranes of the upper respiratory tract, decreases lacrimation, and relieves itching in the eyes and nose.

Pharmacokinetics

Not studied.

Clinical characteristics.

Indications.

Symptomatic treatment of cold and influenza accompanied by elevated body temperature, chills, headache, nasal discharge and nasal congestion, sneezing, malaise, and body aches.

Contraindications.

Hypersensitivity to the components of the drug or to other xanthine derivatives (theophylline, theobromine). Chronic obstructive pulmonary diseases. Emphysema. Severe cardiovascular diseases, including conduction disorders, marked atherosclerosis, severe forms of ischemic heart disease. Acute myocardial infarction. Peripheral arterial thrombosis. Decompensated heart failure. Ventricular tachycardia. Hyperthyroidism. Severe impairment of liver and/or kidney function. Acute pancreatitis, hepatitis. Stenosing gastric and duodenal ulcers. Congenital hyperbilirubinemia. Severe arterial hypertension. Prostatic adenoma with difficult urination. Obstruction of the urinary bladder neck. Blood disorders (severe anemia, leukopenia), hyperthyroidism. Pyloroduodenal obstruction. Pheochromocytoma. Diabetes mellitus. Bronchial asthma. Closed-angle glaucoma. Glucose-6-phosphate dehydrogenase deficiency. Alcoholism. Increased excitability. Sleep disorders. Epilepsy. Concurrent use with monoamine oxidase inhibitors (MAOIs) and within 2 weeks after discontinuation of such agents. Concurrent use with tricyclic antidepressants, β-blockers. Advanced age of the patient (60 years and older).

Pregnancy or breastfeeding. Children under 12 years of age.

Interaction with other medicinal products and other types of interactions.

The absorption rate of paracetamol may be increased when used concomitantly with metoclopramide and domperidone, and decreased with cholestyramine. Long-term concurrent use enhances the anticoagulant effect of coumarins (e.g., warfarin and other coumarins), increasing the risk of bleeding due to prolonged regular use of paracetamol. Single doses do not show significant effects. Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsants (phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzymes, and isoniazid may enhance the hepatotoxicity of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Paracetamol reduces the effectiveness of diuretics.

Paracetamol should be used with caution when administered concomitantly with flucloxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap (HAGMA) due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions for use").

Do not use concurrently with alcohol.

Phenylephrine hydrochloride interaction with MAO inhibitors causes a hypertensive effect; with tricyclic antidepressants (amitriptyline) – increases the risk of cardiovascular adverse effects; with digoxin and cardiac glycosides – leads to arrhythmias and myocardial infarction. Phenylephrine combined with other sympathomimetics increases the risk of adverse cardiovascular reactions, may reduce the effectiveness of β-blockers and other antihypertensive agents (reserpine, methyldopa), increasing the risk of arterial hypertension and adverse cardiovascular reactions.

Phenylephrine may cause adverse reactions when used concomitantly with indomethacin and bromocriptine (severe arterial hypertension). Concurrent use of phenylephrine hydrochloride with sympathomimetic amines increases the risk of arrhythmias and myocardial infarction.

Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine hydrochloride.

The central nervous system depressant effect of chlorpheniramine maleate may be significantly enhanced when used concomitantly with sedatives, barbiturates, tranquilizers, neuroleptics, anesthetics, narcotic analgesics, and alcohol. Chlorpheniramine maleate enhances the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, and antiparkinsonian agents.

Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents, potentiates the effects of xanthine derivatives, α- and β-adrenergic agonists, and psychostimulants.

Concurrent use of caffeine with MAO inhibitors may cause a dangerous increase in blood pressure.

Cimetidine, hormonal contraceptives, and isoniazid enhance the effects of caffeine.

Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics, and sedatives; it acts as an antagonist of anesthetic agents and other drugs that depress the CNS, and as a competitive antagonist of adenosine and ATP agents. Concurrent use of caffeine with ergotamine improves the absorption of ergotamine in the gastrointestinal tract; with thyroid-stimulating agents – increases thyroid effect. Caffeine reduces serum lithium concentration.

Concurrent use with flucloxacillin increases the risk of metabolic acidosis with a high anion gap, especially in patients with risk factors (see section "Special precautions for use").

Special precautions for use.

Do not exceed the recommended dose.

Avoid concomitant use with other medicinal products intended for symptomatic treatment of cold and influenza, and with medicinal products containing paracetamol.

This medicinal product is not recommended for concomitant use with sedatives, hypnotics, or alcoholic beverages.

The physician should prescribe this medicinal product only after assessing the risk-benefit ratio in the following conditions: arterial hypertension; cardiac arrhythmias; urinary disorders. If the product is used for a prolonged period as directed by a physician, monitoring of liver function and peripheral blood picture is necessary.

When using this product, avoid excessive consumption of coffee, strong tea, other stimulant beverages, and medicinal products containing caffeine. This may cause sleep disturbances, tremor, tension, irritability, and palpitations.

Consult a physician before use if the patient is taking warfarin or similar agents with anticoagulant effects.

Consult a physician regarding the possibility of using this product in patients with impaired kidney or liver function.

Note that in patients with alcoholic liver disease, the risk of hepatotoxic effects of paracetamol is increased; the product may affect laboratory test results for blood glucose and uric acid levels.
In patients with severe infections such as sepsis, associated with reduced glutathione levels, administration of paracetamol increases the risk of metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Immediate medical attention should be sought if these symptoms occur.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe conditions such as severe renal failure and sepsis, or in patients with malnutrition or other causes of glutathione deficiency (e.g., chronic alcoholism), who received paracetamol at therapeutic doses for prolonged periods or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with careful monitoring of the patient. Measurement of urinary 5-oxoproline levels may be helpful in confirming pyroglutamic acidosis as the primary cause of HAGMA in patients with multiple risk factors.

Patients who take analgesics daily for mild forms of arthritis should consult a physician.

If symptoms persist, consult a physician.

If headache becomes persistent, consult a physician.

The medicinal product contains sorbitol solution (E 420). If the patient has been diagnosed with intolerance to certain sugars, consult a physician before taking this medicinal product.

The medicinal product contains the colouring agent Ponceau 4R (E 124), which may cause allergic reactions.

Use during pregnancy or breastfeeding.

Contraindicated.

Ability to affect reaction speed when driving or operating machinery.

During treatment with FluCold®-N, driving, operating machinery, and engaging in other potentially hazardous activities should be avoided.

Dosage and Administration.

For adults and children aged 12 years and older, administer 1 tablet every 3–4 hours, but not more than 4 tablets per day. The interval between doses should be at least 4 hours. The duration of treatment should be determined by a physician. The maximum duration of use without medical consultation is 3 days.

Do not take together with medicinal products containing paracetamol.

Children.

The drug is indicated for children aged 12 years and older.

Overdose.

Symptoms of paracetamol overdose. During the first 24 hours, pallor, nausea, vomiting, anorexia, and abdominal pain may appear.
After ingestion of large doses, disorientation, excitement, dizziness, sleep disturbances, cardiac arrhythmias, and pancreatitis may occur. In isolated cases, acute renal failure with tubular necrosis has been reported, manifested by lumbar pain, hematuria, and proteinuria; nephrotoxicity (renal colic, interstitial nephritis) may also occur.

In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and may be fatal.

Ingestion of 10 g or more of paracetamol by adults, especially when combined with alcohol, or more than 150 mg of paracetamol per 1 kg body weight in children, may lead to hepatocellular necrosis, resulting in encephalopathy, hepatic coma, and potentially death. The first clinical signs of hepatonecrosis may appear 12–48 hours after overdose. Disturbances in glucose metabolism and metabolic acidosis may also occur.

Cardiac arrhythmias and pancreatitis have also been reported.

With prolonged use of the drug in high doses, blood-forming organs may develop aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia. Central nervous system effects from high doses may include dizziness, psychomotor agitation, and disorientation. Urinary system effects may include nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).

In case of overdose, prompt medical assistance is required. The patient should be immediately hospitalized, even if early symptoms of overdose are absent. Symptoms may be limited to nausea and vomiting or may not reflect the severity of overdose or risk of organ damage. Administration of activated charcoal should be considered if an excessive dose of paracetamol was ingested within the past 1 hour. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol ingestion, but the maximum protective effect is achieved when administered within 8 hours after ingestion. The efficacy of the antidote decreases sharply after this time. If necessary, N-acetylcysteine should be administered intravenously according to the established dosage regimen. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside the hospital.

Overdose of phenylephrine hydrochloride causes hyperhidrosis, psychomotor agitation or CNS depression, headache, dizziness, drowsiness, impaired consciousness, arrhythmias, tremor, hyperreflexia, seizures, nausea, vomiting, irritability, restlessness, and arterial hypertension.

Overdose of chlorpheniramine maleate may result in anticholinergic (atropine-like) symptoms: mydriasis, photophobia, dryness of skin and mucous membranes, elevated body temperature, and intestinal atony. CNS depression may be accompanied by respiratory depression and cardiovascular disturbances (decreased pulse rate, reduced arterial pressure up to circulatory failure).

Large doses of caffeine may cause epigastric pain, vomiting, diuresis, rapid breathing, extrasystoles, tachycardia or cardiac arrhythmia, and effects on the central nervous system (dizziness, insomnia, nervous excitement, irritability, mood disturbances, anxiety, tremor, seizures). Clinically significant symptoms of caffeine overdose may also be associated with liver damage caused by paracetamol.

Treatment. Within the first 6 hours after suspected overdose, gastric lavage should be performed, followed by hospitalization of the patient.

Within the first 8 hours after overdose: administration of oral methionine or intravenous cysteamine or N-acetylcysteine; symptomatic therapy; in case of severe arterial hypertension, use of α- and β-adrenoblockers.

Adverse Reactions

Immune system disorders: anaphylaxis; hypersensitivity reactions including skin pruritus, mucocutaneous eruptions (usually generalized rash, erythematous, urticaria), angioneurotic edema; erythema multiforme (including Stevens-Johnson syndrome); toxic epidermal necrolysis (Lyell’s syndrome).

Metabolism and nutrition disorders: metabolic acidosis with high anion gap (frequency unknown).

Nervous system disorders: headache, dizziness, psychomotor agitation, disorientation, anxiety, nervousness, fear, irritability, sleep disturbances, insomnia, somnolence, confusion, hallucinations, depressive states, tremor, paresthesia and heaviness in limbs, tinnitus, epileptic seizures, restlessness; in individual cases – coma, convulsions, dyskinesia, behavioral changes, general weakness.

Respiratory system disorders: bronchospasm in patients sensitive to acetylsalicylic acid (aspirin) and other nonsteroidal anti-inflammatory drugs.

Eye disorders: visual disturbances and accommodation disorders, mydriasis, increased intraocular pressure, dry eyes.

Gastrointestinal disorders: nausea, vomiting, heartburn, dry mouth, epigastric discomfort and pain, diarrhea, constipation, flatulence, hypersalivation, decreased appetite, exacerbation of peptic ulcer.

Hepatobiliary disorders: liver function abnormalities, elevated liver enzyme activity, usually without jaundice, hepatotoxic effects, hepatonecrosis (with high-dose administration).

Endocrine system disorders: hypoglycemia, up to hypoglycemic coma.

Blood and lymphatic system disorders: anemia, including hemolytic; thrombocytopenia, agranulocytosis, neutropenia, pancytopenia, leukopenia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), bruising or bleeding.

Renal and urinary disorders: nephrotoxicity, interstitial nephritis, papillary necrosis, micturition disorders, dysuria, urinary retention, aseptic pyuria, renal colic.

Cardiovascular disorders: arterial hypertension, tachycardia or reflex bradycardia, arrhythmia, dyspnea, chest pain, palpitations.

Other: increased creatinine clearance, increased excretion of sodium and calcium, nasal congestion; possible false elevation of blood uric acid levels when measured by the Bittner method; slight increase in urinary 5-hydroxyindoleacetic acid, vanillylmandelic acid, and catecholamines.

Concomitant use of the drug at recommended doses with caffeine-containing products may enhance caffeine-related adverse effects such as dizziness, increased excitability, insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disturbances, and tachycardia.

Description of selected adverse reactions

Metabolic acidosis with high anion gap

Cases of metabolic acidosis with high anion gap due to pyroglutamic acidosis have been observed in patients with risk factors who were taking paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in such patients.

Shelf life. 4 years.

Storage conditions.

Store in a dry, protected from light and inaccessible to children place at a temperature not exceeding 25 °C.

Packaging.

No. 4 – 4 tablets per strip in a paper envelope;

No. 12 – 4 tablets per strip, 3 strips in a cardboard box;

No. 200 – 4 tablets per strip in a paper envelope, 50 envelopes in a cardboard box.

Dispensing category.

No. 4; No. 12 – without prescription, No. 200 – by prescription.

Manufacturer.

Nabros Pharma Pvt. Ltd.

Manufacturer's address and location of business activity.

Survey No. 110/A/2 Amrit Farm, Jaynupasraya, near Coca Cola factory, N.H. No. 8, Kajipura – 387411, Kheda, India.