Duocold set, lemon day 9 pcs./night 3 pcs.

Pharmacotherapeutic group

Acute respiratory infections and “colds” symptoms remedy (vitamin+calcium-phosphate metabolism regulator+non-narcotic analgesic+angioprotector+alpha-adrenomimetic+H1-histamine receptor blocker)

ATX code: N02BE51

Pharmacological properties

Pharmacodynamics

It is a combined preparation, the action of which is due to its constituent components, with antipyretic, anti-inflammatory, analgesic, anti-allergic, angioprotective and vasoconstrictor action. Eliminates symptoms of “colds”. Narrowes nasal vessels, eliminates nasal mucosal edema.

Ascorbic acid (vitamin C) – make up for the increased need for vitamin C in colds and flu, especially in the initial stages of the disease. It increases resistance to infectious diseases, participates in the regulation of redox processes, promotes normal capillary permeability, blood coagulation and tissue regeneration.

Calcium gluconate replenishes the lack of calcium ions required for the transmission of nerve impulses, the contraction of skeletal and smooth muscles, myocardial function, bone formation, blood clotting. It has anti-allergic effect, prevents the development of increased permeability and fragility of blood vessels that cause hemorrhagic processes in influenza and acute respiratory viral infections.

Paracetamol – non-narcotic analgesic, blocks structural enzyme cyclooxygenase-1 (COX-1) and inducible enzyme (COX-2) mainly in the central nervous system, affecting the centers of pain and thermoregulation. It has analgesic and antipyretic effects. It reduces headache, muscle pain and fever. It does not affect platelet function and hemostasis.

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

Phenylephrine is a symptomatic agent, stimulates postsynaptic alpha1-adrenoreceptors, has a moderate vasoconstrictor effect, reduces swelling and hyperemia of the nasal mucosa, restores free breathing, reduces pressure in the paranasal cavities and middle ear.

Pheniramine – is an anti-allergic agent – a blocker of H1-histamine receptors. It reduces nasal congestion, sneezing, lacrimation, itching and red eyes. It has a moderate sedative effect.

Pharmacokinetics

Ascorbic acid

Ascorbic acid.Absorption

Askorbic acid is completely absorbed from the gastrointestinal tract after ingestion.

Distribution

Widely distributed in body tissues. Time of reaching maximum plasma concentration (TSmax) after oral administration is 4 hours. Binding with blood plasma proteins is 25%. The concentration of ascorbic acid in leukocytes and platelets is higher than in erythrocytes and plasma. It penetrates through the placenta and enters the breast milk.

Metabolism and excretion

Metabolized mainly in the liver to deoxyascorbic acid and then to oxalic acid and ascorbate-2-sulfate. It is excreted by the kidneys unchanged and as metabolites.

Calcium gluconate

Approximately 1/5-1/3 of 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 that can bind calcium ions. Absorption of calcium ions increases with calcium deficiency and the use of a diet with reduced calcium ions. About 20% is excreted by the kidneys, the rest (80%) by the intestine.

Paracetamol

absorption

Paracetamol is quickly and almost completely absorbed from the gastrointestinal tract after oral administration. Maximum plasma concentrations are reached 10-60 minutes after oral administration.

Distribution

Paracetamol is distributed in most body tissues, penetrates the placenta and is present in breast milk. In therapeutic concentrations, the binding to plasma proteins is insignificant, increasing with increasing concentrations.

Metabolism

It is subjected to primary metabolism in liver, eliminated mainly by kidneys as glucuronide and sulfate compounds. Elimination half-life is 1-3 hours.

Rutozide

In oral administration 10-15% of the dose is absorbed, maximum plasma concentration is reached after 1-9 hours, half-life is 10-25 hours; excreted mainly with bile.

Phenylephrine

absorption and metabolism

It is absorbed from the gastrointestinal tract and undergoes primary metabolism in the intestine and liver. Maximum plasma concentrations are reached between 45 minutes and 2 hours.

Elimation

Extracted almost completely by the kidneys as sulfate compounds. The elimination half-life is 2-3 hours.

Pheniramine

Distribution

After oral administration the maximum plasma concentration is reached after 1-2.5 hours. The elimination half-life in the final phase is 16-19 hours.

Elimation

Extracted by the kidneys (70-83%) as unchanged substance or metabolites.

Indications

Symptomatic treatment of infectious and inflammatory diseases: ARI (acute respiratory viral infection), including influenza and “colds” accompanied by high body temperature, chills, headache, pain in the joints and muscles, runny nose, stuffy nose, sneezing and pain in the throat and sinuses.

Active ingredient

Ascorbic acid, Calcium gluconate, Paracetamol, Rutozide, Phenylephrine

Composition

Powder for the preparation of a solution for oral administration “Day”: One bag of “Day” contains:

acting substances: paracetamol – 325 mg, ascorbic acid – 200 mg, calcium gluconate monohydrate – 200 mg, rutoside – 20 mg, phenylephrine hydrochloride – 10 mg; excipients: mannitol, sodium citrate, Lemon or Cranberry flavoring, citric acid monohydrate, aspartame, povidone K-30.

Powder for preparation of oral solution “Night”: One bag of “Night” contains:

acting ingredients: paracetamol – 500 mg, ascorbic acid – 200 mg, calcium gluconate monohydrate – 200 mg, rutoside – 20 mg, pheniramine maleate – 20 mg, phenylephrine hydrochloride – 10 mg;

complementary substances: mannitol, sodium citrate, Lemon or Cranberry flavoring, citric acid monohydrate, aspartame, povidone K-30.

How to take, the dosage

Internal. Dissolve the contents of the sachet in one cup (200 ml) of hot, but not boiling, water. Use immediately after dissolving. Stir the solution before drinking.

Adults and children over 12 years take 1 sachet “Day” every 4-6 hours during the day, but no more than 3 times a day, and 1 sachet “Night” in the evening before going to bed (no more than 1 time a day) for no more than 3 days. If there is no relief of symptoms within 3 days after starting the drug, you should see a doctor.

Patients with hepatic impairment

Patients with impaired liver function or Gilbert syndrome need to reduce the dose or increase the interval between doses of the drug.

Patients with renal impairment

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

Elderly patients

Dose adjustment is not necessary in elderly patients.

Interaction

Influence of ascorbic acid

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

Concomitant use of oral contraceptives decreases the concentration of ascorbic acid in plasma.

Possible increase in plasma concentrations of ethinylestradiol when used concomitantly with oral contraceptives.

In concomitant use with iron preparations, ascorbic acid, due to its reducing properties, converts trivalent to divalent iron, which helps to improve its absorption.

Ascorbic acid in high doses may decrease urinary pH, which with concomitant use reduces the tubular reabsorption of amphetamine and tricyclic antidepressants.

Concomitant use of acetylsalicylic acid reduces absorption of ascorbic acid by about a third.

Concomitant use with warfarin may reduce the effects of warfarin.

Influence of calcium gluconate

In concomitant use calcium gluconate slows absorption of tetracyclines, digoxin, oral iron drugs (interval between their doses should be at least 2 hours).

In concomitant use with colestyramine the absorption of calcium from the gastrointestinal tract is decreased.

Calcium gluconate during concomitant use decreases hypotensive effect of calcium channel blockers (IV administration of calcium gluconate before and after verapamil decreases its hypotensive effect).

Parenteral administration of calcium gluconate is not recommended during treatment with cardiac glycosides (potentiation of cardiotoxic effect is possible). Concomitant use with quinidine may slow intraventricular conduction and increase quinidine toxicity.

In combination with thiazide diuretics calcium gluconate may increase hypercalcemia, decrease of calcitonin effect in hypercalcemia, decrease phenytoin bioavailability.

Influence of paracetamol

Accelerates the effects of MAO inhibitors, sedatives, ethanol.

The risk of hepatotoxic effects of paracetamol increases with concomitant administration of barbiturates, phenytoin, phenobarbital, carbamazepine, rifampicin, isoniazid, zidovudine and other inducers of microsomal liver enzymes.

The anticoagulant properties of warfarin and other coumarins may be enhanced with long-term regular use of paracetamol, increasing the risk of bleeding. Single administration of paracetamol has no such effect. Metoclopramide increases the absorption rate of paracetamol and increases the plasma concentration of paracetamol to a maximum. Similarly, domperidone may increase the absorption rate of paracetamol.

When chloramphenicol and paracetamol are used together the elimination half-life of chloramphenicol may be increased.

Paracetamol may decrease the bioavailability of lamotrigine with possible reduction of its action due to induction of its hepatic metabolism. Absorption of paracetamol may be reduced when concomitantly taken with colestyramine, but this can be avoided if colestyramine is taken one hour later than paracetamol.

The regular use of paracetamol concomitantly with zidovudine may cause neutropenia and increase the risk of liver damage. Probenecid affects the metabolism of paracetamol. In patients taking probenecid concomitantly, the dose of paracetamol should be reduced.

The hepatotoxicity of paracetamol may be increased with chronic or excessive alcohol consumption. Paracetamol may affect the results of a uric acid test using a precipitating reagent phosphovolframate.

Influence of rutoside

Ascorbic acid enhances the effects of rutoside.

Effects of phenylephrine

The drug is contraindicated in patients who are taking or have taken MAOI inhibitors within the last two weeks. MAOI inhibitors, tricyclic antidepressants (e.g., amitriptyline), ergot alkaloids, and sympathomimetics increase the pressor effect, and the latter and arrhythmogenicity of phenylephrine.

Phenylephrine may decrease the effectiveness of beta-adrenal blockers and other hypotensive drugs (e.g., debrisochine, guanethidine, reserpine, methyldopa). There is an increased risk of arterial hypertension.

The concomitant use of phenylephrine with digoxin and other cardiac glycosides may increase the risk of arrhythmia or myocardial infarction.

The thyroid hormones increase (reciprocally) the risk of coronary artery disease (especially in coronary atherosclerosis).

Alpha-adrenoblockers (phentolamine), phenothiazines, furosemide and other diuretics prevent vasoconstriction.

Influence of pheniramine

The effects of other substances on the central nervous system (e.g., MAO inhibitors, tricyclic antidepressants, alcohol, antiparkinsonian drugs, barbiturates, tranquilizers and narcotic drugs) may be enhanced. Pheniramine may inhibit the effect of anticoagulants.

Special Instructions

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

Patients should consult a physician if:

• have bronchial asthma, emphysema, or chronic bronchitis;
• symptoms do not resolve 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 contains 200 mg of sodium citrate per bag. This should be taken into consideration by patients on a sodium diet.

The product should not be used from damaged sachets.

The drug should not be taken at the same time as other drugs containing paracetamol.

Influence on the ability to drive vehicles, machinery

Pheniramine contained in the contents of the bag “Night” may cause drowsiness, so during treatment it is not recommended to drive and engage in other activities requiring concentration and high speed of psychomotor reactions.

Synopsis

Powder from light yellow to yellow in color with a characteristic odor with the presence of white crystals. There may be bright yellow flecks and lumps, easily crumbling on pressure.

The appearance of the drug solution. Transparent or opalescent solution of light yellow color with characteristic odor. Yellow undissolved particles are possible.

Contraindications

• high sensitivity to paracetamol, rutozide, phenylephrine, pheniramine, ascorbic acid and other constituents of the drug;
• concurrent use of paracetamol-containing drugs;
• administration of tricyclic antidepressants, beta-adrenal blockers and other sympathomimetic drugs.concomitant use of tricyclic antidepressants, beta-adrenoblockers, other sympathomimetic drugs;
• concomitant use of tricyclic antidepressants, beta-adrenoblockers, other sympathomimetic drugssimultaneous or within the previous 2 weeks taking monoamine oxidase (MAO) inhibitors;
• severe cardiovascular disease;
• arterial hypertension;
• closed angle glaucoma;
• tendency to thrombosis;
• pheochromocytoma, hyperthyroidism;
• portal hypertension;
• alcoholism;
• sugar diabetes;
• pregnancy, period of breastfeeding;
• phenylketonuria;
• children under 12 years of age;
• hypercalcemia (calcium concentration should not exceed 12 mg %);
• Severe hypercalciuria;
• nephrourolithiasis (calcium);
• current use of cardiac glycosides (risk of arrhythmias).

Cautions

• expressed coronary artery atherosclerosis;
• cardiovascular disease;
• acute hepatitis;
• hemolytic anemia;
• hepatitissevere liver or kidney disease;
• prostate hyperplasia, difficulty urinating due to prostate hypertrophy;
• blood disorders;
• deficiency of glucose-6-phosphate dehydrogenase;
• congenital hyperbilirubinemia (Gilbert, Dubin-Johnson, and Rotor syndromes);
• bronchial asthma;
• Chronic malnutrition (caloric deficiency) and dehydration;
• pyloroduodenal obstruction;
• stenotic gastric and/or duodenal ulcer;
• Epilepsy;
• current use of drugs that can adversely affect the liver (barbiturates, phenytoin, phenobarbital, carbamazepine, rifampicin, isoniazid, zidovudine and other inducers of microsomal liver enzymes).

.

Side effects

The incidence of side effects is mostly dose-dependent. Classification of the frequency of side effects (WHO):
very common ≥1/10;
common ≥1/100 to < 1/10; infrequent ≥1/1000 to < 1/100; rare ≥1/10000 to < 1/1000;
very rare < 1/10000, including individual reports;
frequency is unknown – the incidence cannot be determined from available data.

The drug is usually well tolerated in therapeutic doses, but the following side effects may occur.

Blood and lymphatic system disorders: very rarely – thrombocytopenia, agranulocytosis, leukopenia, pancytopenia.

Intune system disorders: rare – hypersensitivity reactions (rash, dyspnea, anaphylactic shock), angioedema;
incidence unknown – anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Mental disorders: rare – increased excitability, sleep disturbance (when taking the contents of the sachets “Day”).

Nervous system disorders: often – drowsiness (when taking the contents of sachets “Night”), rarely – dizziness, headache.

Visual organ disorders: rare – mydriasis, accommodation paresis, increased intraocular pressure.

Cardiac disorders: rare – tachycardia, palpitations.

Vascular disorders: rarely – increase in blood pressure.

Gastrointestinal disorders: frequently – nausea, vomiting; rarely – dry mucous membrane of the mouth, constipation, abdominal pain, diarrhea.

Liver and biliary tract disorders: rare – increase of liver enzymes activity.

Skin and subcutaneous tissue disorders: rare – rash, itching, erythema, urticaria.

River and urinary tract disorders: rarely – difficulty in urination.

General disorders and reactions at the site of administration: rarely – malaise.

If any of the side effects listed in the instructions worsen, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

The most dangerous symptoms of drug overdose can be caused by paracetamol.

Paracetamol

Symptoms (occur after a single dose of 7.5-10 g of paracetamol): In severe cases of overdose, paracetamol has hepatotoxic effects, including can cause liver necrosis. Also overdose can cause nephropathy with irreversible liver failure.

The severity of overdose depends on the dose, so patients should be warned against taking paracetamol-containing drugs at the same time. The risk of poisoning is especially high in elderly patients, children, patients with liver disease, in cases of chronic alcoholism, in patients with chronic malnutrition (caloric deficit) and in patients taking microsomal oxidation inducers in the liver.

Paracetamol overdose can lead to liver failure, encephalopathy, coma, and death.

The symptoms of paracetamol overdose in the first 24 hours are pale skin, nausea, vomiting, anorexia, seizures. Abdominal pain may be the first sign of liver damage and is usually not manifested during the first 24-48 hours and may sometimes appear later, 4-6 days later, on average 72-96 hours after taking the drug. Impaired glucose metabolism and metabolic acidosis may also occur. Even in the absence of liver damage, acute renal failure and acute tubular necrosis may develop. Cases of cardiac arrhythmias and development of pancreatitis have been reported in paracetamol overdose.

Treatment: administration of acetylcysteine intravenously or orally as an antidote, gastric lavage, and oral methionine administration may have a positive effect for at least the first 48 hours after overdose.

The administration of activated charcoal, respiratory and circulatory monitoring is recommended. Diazepam may be administered if seizures develop.

Ascorbic acid

Symptoms: If more than 1 g per day is taken, heartburn, diarrhea, difficulty urinating or staining urine red, hemolysis (in patients with glucose-6-phosphate dehydrogenase deficiency) may occur.

Calcium gluconate

Symptoms: The development of hypercalcemia: nausea, vomiting, severe weakness, thirst, drowsiness, disorientation, confusion, renal failure. Maximum daily dose for adults and children over 12 years old is 9 g.

Treatment: Calcitonin intravenous drip 5-10 IU/kg per day (the drug is diluted in 500 ml of isotonic sodium chloride solution, administered for 6 hours).

Pheniramine and phenylephrine (overdose symptoms are combined because of the risk of mutual potentiation of the parasympatholytic effect of pheniramine and the sympathomimetic effect of phenylephrine in case of drug overdose).

Symptoms: somnolence which is later joined by anxiety (especially in children), visual disturbances, rash, nausea, vomiting, headache, increased excitability, dizziness, insomnia, circulatory disorders, coma, seizures, behavior changes, high or low blood pressure, bradycardia. Cases of atropine-like “psychosis” have been reported in cases of pheniramine overdose.

Treatment. There is no specific antidote. Routine measures of care are necessary, including administration of activated charcoal, saline laxatives, and measures to support cardiac and respiratory function. Psychostimulants (methylphenidate) should not be administered because of the risk of seizures. Vasopressor drugs may be used in case of hypotension.

In case of high blood pressure, intravenous administration of alpha-adrenoblockers is possible, because phenylephrine is a selective agonist of alpha1-adrenoreceptors, therefore, the hypertensive effect in case of phenylephrine overdose should be treated by blocking the alpha-adrenoreceptors. Diazepam should be used if seizures develop.

Pregnancy use

The drug is not recommended for use during pregnancy and breastfeeding, due to the lack of data on the safe use of the drug in these persons.