Caffetin^® Cold (Tablets) Instructions for Use

Marketing Authorization Holder

Alkaloid AD Skopje (Republic of North Macedonia)

ATC Code

R01BA52 (Pseudoephedrine in combination with other drugs)

Dosage Form

Caffetin® Cold

Film-coated tablets: 10 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets blue in color, oblong, biconvex, with a score on one side.

Excipients: hypromellose (in the ascorbic acid granulate*), microcrystalline cellulose, pregelatinized starch, povidone K30, colloidal silicon dioxide, croscarmellose sodium, talc, magnesium stearate.

Coating composition Opadry white 85F18422 (partially hydrolyzed polyvinyl alcohol, macrogol 3550, titanium dioxide, talc), Opadry blue 85F20400 (partially hydrolyzed polyvinyl alcohol, macrogol 3550, titanium dioxide, talc, dye indigotine (E132)).

* Ascorbic acid is used in the form of a granulate: 1 g of granulate contains 950 mg of ascorbic acid (95%) and 50 mg of hypromellose (5%).

10 pcs. – blister packs (1) – cardboard packs.

Clinical-Pharmacological Group

Drug for symptomatic therapy of acute respiratory diseases

Pharmacotherapeutic Group

Remedy for the relief of acute respiratory disease and “common cold” symptoms (non-narcotic analgesic + sympathomimetic agent + opioid antitussive + vitamin)

Pharmacological Action

Paracetamol has analgesic and antipyretic effects. In the central nervous system, it blocks cyclooxygenase, acting on pain and thermoregulation centers. Unlike non-steroidal anti-inflammatory drugs, paracetamol has virtually no anti-inflammatory effect. It does not irritate the gastric and intestinal mucosa. It does not affect water-salt metabolism because it does not affect the synthesis of prostaglandins in peripheral tissues.

Pseudoephedrine promotes vasoconstriction of the nasal and pharyngeal mucosa, reduces swelling, which leads to a decrease in nasal secretion and relief of nasal breathing.

Dextromethorphan acts on the cough center and increases the cough threshold, leading to a reduction in dry cough associated with irritation of the nasopharyngeal mucosa in most “common cold” illnesses.

Ascorbic acid replenishes vitamin C deficiency during “common cold” illnesses.

Pharmacokinetics

The absorption of paracetamol occurs mainly in the small intestine, and the maximum plasma concentration is usually reached 0.5-1.5 hours after oral administration. The half-life of paracetamol from plasma is 1.5-2.5 hours. It is metabolized in the liver (90-95%): 80% undergoes conjugation reactions with glucuronic acid and sulfates to form inactive metabolites; 17% undergoes hydroxylation to form 8 active metabolites, which conjugate with glutathione to form inactive metabolites. With a deficiency of glutathione, these metabolites can block the enzyme systems of hepatocytes and cause their necrosis. The isoenzyme CYP2E1 is also involved in the metabolism of the drug, T_1/2 – 1-4 hours. It is excreted by the kidneys in the form of metabolites, mainly conjugates, with only 3% unchanged. In elderly patients, the clearance of the drug decreases and T_1/2 increases.

Pseudoephedrine is well absorbed after oral administration, with maximum plasma concentrations reached in 1.5-2 hours. The plasma half-life is approximately 5.5 hours. Pseudoephedrine is partially metabolized in the liver to form an active metabolite and is excreted in the urine.

Dextromethorphan is well absorbed after oral administration, and the maximum plasma concentration is usually reached 2 hours after dose administration. Dextromethorphan is metabolized in the liver and excreted in the urine unchanged and as metabolites.

Ascorbic acid is completely absorbed in the gastrointestinal tract and is well distributed in body tissues. Ascorbic acid is reversibly oxidized to dehydroascorbic acid and is partially metabolized to ascorbate-2-sulfate; it is excreted in the urine.

Indications

• Symptomatic treatment of the common cold and influenza (headache, muscle pain, sore throat, elevated body temperature, dry cough, runny nose, nasal and sinus congestion).

ICD codes

Dosage Regimen

The recommended dose of Caffetin^® Cold for adults and children over 12 years of age is one tablet 4 times a day. Two tablets can also be taken at once. The interval between doses should be at least 4 hours. The maximum single dose is 2 tablets, and the maximum daily dose is 2 tablets 4 times within 24 hours.

If fever persists for more than 3 days from the start of treatment, and cough for more than 5 days, a doctor should be consulted.

Adverse Reactions

From the digestive system nausea, dry mouth, rarely – epigastric pain; with long-term use in large doses – hepatotoxicity.

From the CNS drowsiness, irritability, agitation, rarely – dizziness.

Allergic reactions skin rash, skin itching, urticaria, angioedema.

From the cardiovascular system increased blood pressure, tachycardia.

From the hematopoietic system rarely – anemia, thrombocytopenia, agranulocytosis; with long-term use in large doses – hemolytic anemia, aplastic anemia, pancytopenia.

From the urinary system with long-term use in large doses – nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Contraindications

• Hypersensitivity to the drug or any of its components;
• Arterial hypertension, coronary artery disease, angina pectoris;
• Severe liver or kidney dysfunction, hepatitis;
• Concomitant use of MAO inhibitors (monoamine oxidase), antidepressants, antiparkinsonian drugs;
• Use of MAO inhibitors (monoamine oxidase) in the preceding two weeks before starting the drug;
• Congenital glucose-6-phosphate dehydrogenase deficiency;
• Children under 12 years of age;
• Pregnancy, lactation period.

With caution benign hyperbilirubinemia (including Gilbert’s syndrome), viral hepatitis, alcoholism, arrhythmias, prostatic hyperplasia with urinary retention, diabetes mellitus, hyperthyroidism, bronchial asthma, COPD (chronic obstructive pulmonary disease), debilitated and emaciated patients.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction.

Use in Renal Impairment

Contraindicated in severe kidney dysfunction.

Pediatric Use

Contraindicated in children under 12 years of age.

Special Precautions

During treatment, peripheral blood counts and liver functional state should be monitored.

During treatment, it is necessary to refrain from consuming ethanol (possible development of hepatotoxic effects) and caffeine, driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms. Pseudoephedrine – irritability, anxiety, tremor, convulsions, arrhythmias, arterial hypertension.

Paracetamol (especially in patients with impaired kidney and liver function) – pale skin, anorexia, nausea, vomiting, impaired liver function.

Dextromethorphan – nausea, vomiting, dizziness, drowsiness, visual disturbances, lethargy, impaired coordination of movement, difficulty breathing.

Treatment. Gastric lavage within the first 6 hours, followed by the administration of activated charcoal, symptomatic therapy, administration of SH-group donors and glutathione synthesis precursors – methionine 8-9 hours after overdose and acetylcysteine – after 12 hours.

Drug Interactions

Concomitant use of paracetamol in high doses enhances the effect of anticoagulant drugs.

Inducers of microsomal oxidation in the liver (phenytoin, ethanol, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants) and hepatotoxic drugs increase the production of hydroxylated active metabolites of paracetamol, which may lead to the development of severe intoxications even with a small dose.

Long-term use of barbiturates reduces the effectiveness of paracetamol.

Concomitant long-term administration of paracetamol in high doses and salicylates increases the risk of kidney and bladder cancer. Long-term combined use of paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of “analgesic” nephropathy and renal papillary necrosis, accelerating the onset of end-stage renal failure.

Diflunisal increases the plasma concentration of paracetamol by 50%, thereby increasing the risk of hepatotoxicity.

When pseudoephedrine is used concomitantly with other sympathomimetic drugs, an additive effect and development of toxic effects are possible; with monoamine oxidase inhibitors – the development of a hypertensive crisis is possible (the drug can be used no earlier than 2 weeks after discontinuation of monoamine oxidase inhibitors).

Propranolol may enhance the pressor effect of pseudoephedrine; pseudoephedrine may reduce the hypotensive effect of reserpine, methyldopa, mecamylamine, and Veratrum alkaloids.

Amiodarone, fluoxetine, quinidine, by inhibiting the cytochrome P450 system, may increase the concentration of dextromethorphan in the blood.

Storage Conditions

Store at a temperature not exceeding 25°C (77°F), in a place inaccessible to children.

Shelf Life

Shelf life – 2 years

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.