Duocold^® (Powder) Instructions for Use

Marketing Authorization Holder

Vertex, JSC (Russia)

ATC Code

N02BE51 (Paracetamol in combination with other drugs, excluding psycholeptics)

Dosage Forms

	Duocold®	Powder for preparation of oral solution with lemon flavor: sachet 5 g 3, 4, 6, 8, 9, 12, 15, 16 or 20 pcs.
		Set of powders for preparation of oral solution with cranberry flavor: sachet 5 g 3, 4, 6, 8, 9, 12, 15, 16 or 20 pcs.

Dosage Form, Packaging, and Composition

Powder for preparation of oral solution “Day” from light yellow to yellow in color, with a characteristic odor, with the presence of white crystals; inclusions of bright yellow color and lumps that easily crumble when pressed are allowed; prepared solution: clear or opalescent, light yellow in color, with a characteristic odor; the presence of undissolved yellow particles is allowed.

Excipients : mannitol, sodium citrate, Lemon flavor, citric acid monohydrate, aspartame, povidone K-30.

Powder for preparation of oral solution “Night” from light yellow to yellow in color, with a characteristic odor, with the presence of white crystals; inclusions of bright yellow color and lumps that easily crumble when pressed are allowed; prepared solution: clear or opalescent, light yellow in color, with a characteristic odor; the presence of undissolved yellow particles is allowed.

Excipients : mannitol, sodium citrate, Lemon flavor, citric acid monohydrate, aspartame, povidone K-30.

5 g – heat-sealed sachets (3) (in a set: 2 “Day” sachets and 1 “Night” sachet) – cardboard packs.
5 g – heat-sealed sachets (4) (in a set: 2 “Day” sachets and 2 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (4) (in a set: 3 “Day” sachets and 1 “Night” sachet) – cardboard packs.
5 g – heat-sealed sachets (6) (in a set: 3 “Day” sachets and 3 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (6) (in a set: 4 “Day” sachets and 2 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (8) (in a set: 4 “Day” sachets and 4 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (8) (in a set: 6 “Day” sachets and 2 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (9) (in a set: 6 “Day” sachets and 3 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (12) (in a set: 9 “Day” sachets and 3 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (15) (in a set: 10 “Day” sachets and 5 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (16) (in a set: 12 “Day” sachets and 4 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (20) (in a set: 10 “Day” sachets and 10 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (20) (in a set: 15 “Day” sachets and 5 “Night” sachets) – cardboard packs.

Powder for preparation of oral solution “Day” from light yellow to yellow in color, with a characteristic odor, with the presence of white crystals; inclusions of bright yellow color and lumps that easily crumble when pressed are allowed; prepared solution: clear or opalescent, light yellow in color, with a characteristic odor; the presence of undissolved yellow particles is allowed.

Excipients : mannitol, sodium citrate, Cranberry flavor, citric acid monohydrate, aspartame, povidone K-30.

Powder for preparation of oral solution “Night” from light yellow to yellow in color, with a characteristic odor, with the presence of white crystals; inclusions of bright yellow color and lumps that easily crumble when pressed are allowed; prepared solution: clear or opalescent, light yellow in color, with a characteristic odor; the presence of undissolved yellow particles is allowed.

Excipients : mannitol, sodium citrate, Cranberry flavor, citric acid monohydrate, aspartame, povidone K-30.

5 g – heat-sealed sachets (3) (in a set: 2 “Day” sachets and 1 “Night” sachet) – cardboard packs.
5 g – heat-sealed sachets (4) (in a set: 2 “Day” sachets and 2 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (4) (in a set: 3 “Day” sachets and 1 “Night” sachet) – cardboard packs.
5 g – heat-sealed sachets (6) (in a set: 3 “Day” sachets and 3 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (6) (in a set: 4 “Day” sachets and 2 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (8) (in a set: 4 “Day” sachets and 4 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (8) (in a set: 6 “Day” sachets and 2 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (9) (in a set: 6 “Day” sachets and 3 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (12) (in a set: 9 “Day” sachets and 3 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (15) (in a set: 10 “Day” sachets and 5 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (16) (in a set: 12 “Day” sachets and 4 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (20) (in a set: 10 “Day” sachets and 10 “Night” sachets) – cardboard packs.
5 g – heat-sealed sachets (20) (in a set: 15 “Day” sachets and 5 “Night” sachets) – cardboard packs.

Clinical-Pharmacological Group

Drug for symptomatic therapy of acute respiratory diseases

Pharmacotherapeutic Group

Acute respiratory diseases and “common cold” symptoms elimination agent (vitamin + calcium-phosphorus metabolism regulator + non-narcotic analgesic agent + angioprotector + alpha-adrenergic agonist + H1-histamine receptor blocker)

Pharmacological Action

A combined drug, the action of which is due to its constituent components, has antipyretic, anti-inflammatory, analgesic, antiallergic, angioprotective and vasoconstrictive effects. Eliminates cold symptoms. Constricts nasal vessels, eliminates swelling of the nasal mucosa.

Ascorbic acid (vitamin C) – replenishes the increased need for vitamin C in colds and influenza, especially in the initial stages of the disease. Increases the body’s resistance to infectious diseases, participates in the regulation of redox processes, promotes normal capillary permeability, blood clotting, tissue regeneration.

Calcium Gluconate – replenishes the deficiency of calcium ions necessary for the process of nerve impulse transmission, contraction of skeletal and smooth muscles, myocardial activity, bone tissue formation, blood clotting. Has an antiallergic effect, prevents the development of increased permeability and fragility of blood vessels that cause hemorrhagic processes in influenza and ARVI.

Paracetamol – a non-narcotic analgesic, blocks the structural enzyme COX-1 and the inducible enzyme COX-2 mainly in the central nervous system, affecting the centers of pain and thermoregulation. Has analgesic and antipyretic effects. Reduces headache and muscle pain, fever manifestations. Does not affect platelet function and hemostasis.

Rutoside – is an angioprotector. Reduces capillary permeability, swelling and inflammation, strengthens the vascular wall. Prevents the development of increased permeability and fragility of blood vessels that cause hemorrhagic processes. Rutoside participates in redox processes, has antioxidant properties, prevents oxidation and promotes the deposition of ascorbic acid in tissues.

Phenylephrine – a symptomatic agent, stimulates postsynaptic alpha₁-adrenergic receptors, has a moderate vasoconstrictive effect, reduces swelling and hyperemia of the nasal mucosa, restores free breathing, reduces pressure in the paranasal sinuses and middle ear.

Pheniramine – is an antiallergic agent – a blocker of histamine H₁-receptors. Reduces the feeling of nasal congestion, sneezing, lacrimation, itching and redness of the eyes. Has a moderate sedative effect.

Pharmacokinetics

Ascorbic acid: after oral administration, Ascorbic acid is completely absorbed from the gastrointestinal tract. It is widely distributed in body tissues. Time to reach C_max after oral administration is 4 hours. Binding to plasma proteins is 25%. The concentration of ascorbic acid in leukocytes and platelets is higher than in erythrocytes and plasma. Penetrates the placental barrier, excreted in breast milk. Metabolized mainly in the liver to dehydroascorbic acid and then to oxalic acid and ascorbate-2-sulfate. Excreted by the kidneys unchanged and in the form of metabolites.

Calcium Gluconate approximately 1/5-1/3 of the orally administered calcium gluconate is absorbed in the small intestine; this process depends on the presence of vitamin D, pH, dietary characteristics and the presence of factors capable of binding calcium ions. Absorption of calcium ions increases with its deficiency and when using a diet with a reduced content of calcium ions. About 20% is excreted by the kidneys, the rest (80%) – through the intestines.

Paracetamol after oral administration, Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. C_max in blood plasma is reached within 10-60 minutes after oral administration. Paracetamol is distributed in most body tissues, penetrates the placental barrier, and is detected in breast milk. In therapeutic concentrations, binding to plasma proteins is insignificant and increases with increasing concentration. Undergoes primary metabolism in the liver, excreted mainly by the kidneys in the form of glucuronide and sulfate conjugates. T_1/2 is 1-3 hours.

Rutoside when taken orally, 10-15% of the dose is absorbed, C_max in blood plasma is reached within 1-9 hours, T_1/2 is 10-25 hours; excreted mainly with bile.

Phenylephrine is absorbed from the gastrointestinal tract and undergoes primary metabolism in the intestine and liver. C_max in blood plasma is reached in the interval from 45 minutes to 2 hours. Excreted by the kidneys almost completely in the form of sulfate conjugates. T_1/2 is 2-3 hours.

Pheniramine after oral administration, C_max in blood plasma is reached within 1-2.5 hours. T_1/2 in the terminal phase is 16-19 hours. Excreted by the kidneys (70-83%) unchanged or as metabolites.

Indications

Symptomatic treatment of infectious and inflammatory diseases: ARVI, including influenza and the common cold, accompanied by fever, chills, headache, joint and muscle pain, runny nose, nasal congestion, sneezing, and sore throat and nasal sinuses.

ICD codes

Dosage Regimen

Use the Day and Night formulations according to the specific schedule provided in the packaging.

Dissolve the contents of one sachet completely in a glass of warm water immediately before use.

Administer the prepared solution orally.

For adults and children over 12 years of age, use one sachet of the Day formulation 2-3 times during the daytime.

Use one sachet of the Night formulation once in the evening.

Maintain an interval of at least 4 hours between doses.

Do not exceed the maximum daily dose of paracetamol, which is 3000 mg.

The total duration of treatment without medical consultation should not exceed 5 days as an analgesic and 3 days as an antipyretic.

For patients with impaired liver function or Gilbert’s syndrome, reduce the dose or increase the dosing interval.

In the presence of acute renal failure (creatinine clearance less than 10 ml/min), ensure an interval between doses of at least 8 hours.

Adverse Reactions

From the hematopoietic system very rarely – thrombocytopenia, agranulocytosis, leukopenia, pancytopenia.

From the immune system rarely – hypersensitivity reactions (rash, dyspnea, anaphylactic shock), angioedema; frequency unknown – anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Mental disorders rarely – increased excitability, sleep disturbance.

From the nervous system often – drowsiness; rarely – dizziness, headache.

From the organ of vision rarely – mydriasis, accommodation paresis, increased intraocular pressure.

From the cardiovascular system rarely – tachycardia, palpitations, increased blood pressure.

From the digestive system often – nausea, vomiting; rarely – dry oral mucosa, constipation, abdominal pain, diarrhea, increased activity of liver enzymes.

From the skin and subcutaneous tissues rarely – rash, itching, erythema, urticaria.

From the urinary system rarely – difficulty urinating.

General reactions rarely – malaise.

Contraindications

Hypersensitivity to paracetamol, rutoside, phenylephrine, pheniramine, ascorbic acid; simultaneous use of paracetamol-containing drugs; simultaneous use of tricyclic antidepressants, beta-blockers, other sympathomimetic drugs; simultaneous or within the preceding 2 weeks use of MAO inhibitors; severe cardiovascular diseases; arterial hypertension; closed-angle glaucoma; tendency to thrombosis; pheochromocytoma, hyperthyroidism; portal hypertension; alcoholism; diabetes mellitus; pregnancy, breastfeeding period; phenylketonuria; children under 12 years of age; hypercalcemia (calcium concentration should not exceed 12 mg%); severe hypercalciuria; nephrourolithiasis (calcium); simultaneous use of cardiac glycosides (risk of arrhythmias).

With caution

Severe atherosclerosis of the coronary arteries; cardiovascular diseases; acute hepatitis; hemolytic anemia; severe liver or kidney diseases; prostatic hyperplasia, difficulty urinating due to prostatic hypertrophy; blood diseases; glucose-6-phosphate dehydrogenase deficiency; congenital hyperbilirubinemia (Gilbert, Dubin-Johnson and Rotor syndromes); bronchial asthma; chronic malnutrition (deficiency of consumed calories) and dehydration; pyloroduodenal obstruction; stenosing gastric and/or duodenal ulcer; epilepsy; simultaneous use of drugs that can adversely affect the liver (barbiturates, phenytoin, phenobarbital, carbamazepine, rifampicin, isoniazid, zidovudine and other inducers of liver microsomal enzymes).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Patients with impaired liver function or Gilbert’s syndrome should reduce the dose or increase the interval between doses of the drug.

Use in Renal Impairment

In the presence of acute renal failure (creatinine clearance less than 10 ml/min), the interval between doses of the drug should be at least 8 hours.

Pediatric Use

Contraindication: children under 12 years of age.

Geriatric Use

The drug is approved for use in elderly patients.

Special Precautions

To avoid toxic liver damage, the use of this combination should not be combined with the consumption of alcoholic beverages.

Patients should consult a doctor if: they have bronchial asthma, emphysema or chronic bronchitis; symptoms do not go away within 5 days or are accompanied by severe fever lasting for 3 days, rash or persistent headache. These may be signs of more serious disorders.

The drug should not be taken simultaneously with other drugs containing Paracetamol.

Effect on ability to drive vehicles and mechanisms

This combination may cause drowsiness, therefore, during treatment, it is not recommended to drive a car and engage in other activities that require concentration and high speed of psychomotor reactions.

Drug Interactions

Ascorbic acid

With simultaneous use with barbiturates, primidone, tetracycline, the excretion of ascorbic acid in the urine increases.

With simultaneous use of oral contraceptives, the concentration of ascorbic acid in blood plasma decreases.

An increase in the concentration of ethinylestradiol in blood plasma is possible with its simultaneous use as part of oral contraceptives.

With simultaneous use with iron preparations, Ascorbic acid, due to its reducing properties, converts ferric iron to ferrous iron, which contributes to improved absorption.

Ascorbic acid in high doses can decrease urine pH, which, with simultaneous use, reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.

With simultaneous use, acetylsalicylic acid reduces the absorption of ascorbic acid by approximately one-third.

With simultaneous use with warfarin, a reduction in the effects of warfarin is possible.

Calcium Gluconate

With simultaneous oral use, Calcium Gluconate slows the absorption of tetracyclines, digoxin, and oral iron preparations (the interval between their administrations should be at least 2 hours).

With simultaneous use, under the influence of cholestyramine, the absorption of calcium from the gastrointestinal tract is reduced.

Calcium Gluconate with simultaneous use reduces the hypotensive effect of calcium channel blockers (intravenous administration of calcium gluconate before and after verapamil reduces its hypotensive action).

During treatment with cardiac glycosides, parenteral use of calcium gluconate is not recommended (increased cardiotoxic effect is possible).

With simultaneous use with quinidine, slowed intraventricular conduction and increased toxicity of quinidine are possible.

When combined with thiazide diuretics, Calcium Gluconate may enhance hypercalcemia, reduce the effect of calcitonin in hypercalcemia, and reduce the bioavailability of phenytoin.

Paracetamol

It enhances the effects of MAO inhibitors, sedatives, and ethanol.

The risk of the hepatotoxic action of paracetamol increases with the simultaneous use of barbiturates, phenytoin, phenobarbital, carbamazepine, rifampicin, isoniazid, zidovudine, and other inducers of hepatic microsomal enzymes.

The anticoagulant properties of warfarin and other coumarins may be enhanced against the background of long-term regular use of paracetamol, increasing the risk of bleeding. A single dose of paracetamol does not have this effect.

Metoclopramide increases the absorption rate of paracetamol and increases the plasma concentration of paracetamol to the maximum.

Similarly, domperidone may increase the absorption rate of paracetamol.

With the combined use of chloramphenicol and paracetamol, the T_1/2 of chloramphenicol may increase.
Paracetamol may reduce the bioavailability of lamotrigine with a possible reduction in its effect due to the induction of its hepatic metabolism.

The absorption of paracetamol may be reduced with simultaneous use with cholestyramine; however, this can be avoided if cholestyramine is taken one hour after paracetamol.

Regular use of paracetamol simultaneously with zidovudine may cause neutropenia and increase the risk of liver damage.

Probenecid affects the metabolism of paracetamol. In patients taking probenecid simultaneously, the dose of paracetamol should be reduced.

The hepatotoxicity of paracetamol may be enhanced by chronic or excessive alcohol consumption.

Paracetamol may affect the results of the uric acid test using the precipitating reagent phosphotungstate.

Rutoside

Ascorbic acid enhances the effects of rutoside.

Phenylephrine

Contraindicated for use in patients who are taking or have taken MAO inhibitors within the last 2 weeks.

MAO inhibitors, tricyclic antidepressants (e.g., amitriptyline), ergot alkaloids, and sympathomimetics enhance the pressor effect, and the latter also enhance the arrhythmogenicity of phenylephrine.

Phenylephrine may reduce the effectiveness of beta-blockers and other antihypertensive drugs (e.g., debrisoquine, guanethidine, reserpine, methyldopa). The risk of arterial hypertension increases.

Simultaneous use of phenylephrine with digoxin and other cardiac glycosides may increase the risk of arrhythmia or myocardial infarction. Thyroid hormones increase (mutually) the risk of coronary insufficiency (especially with coronary atherosclerosis).

Alpha-blockers (phentolamine), phenothiazines, furosemide, and other diuretics interfere with vasoconstriction.

Pheniramine

Enhancement of the influence of other substances on the CNS is possible (e.g., MAO inhibitors, tricyclic antidepressants, alcohol, antiparkinsonian drugs, barbiturates, tranquilizers, and narcotics).

Pheniramine may inhibit the action of anticoagulants.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.