Ascorbic acid, Paracetamol, Chlorpheniramine

Pharmacological properties

acetaminophen (paracetamol) has an analgesic, antipyretic and mild anti-inflammatory effect. the mechanism of its action is to inhibit the synthesis of prostaglandins and affect the center of thermoregulation in the hypothalamus.

Ascorbic acid (vitamin C) as a key component of the antioxidant and immune defense system increases the adaptive capacity of the body, increases its resistance to infections. Actively involved in the regulation of redox processes, in the metabolism of carbohydrates, the synthesis of steroid hormones, catecholamines and blood coagulation. Enhances collagen synthesis, stimulates regeneration processes, normalizes capillary permeability.

Chlorpheniramine maleate is an antihistamine in the class of alkyl amines, blocker H₁histamine receptors. It has an anti-allergic effect, eliminates rhinorrhea, lacrimation and itching in the eyes and nose. The therapeutic effect develops within 1 hour after oral administration and lasts for 24 hours.

The components of the drug are metabolized independently of each other.

Pharmacokinetics After oral administration, acetaminophen is rapidly absorbed, mainly in the upper digestive tract. It is rapidly distributed in tissues. Binding to blood proteins is 10%. Acetaminophen is metabolized in the liver: most of it binds to glucuronic acid, the smaller to sulfuric acid. The half-life of acetaminophen is 2–2.5 hours. It increases in individuals with liver disease.

Paracetamol is excreted in urine (85% of a single dose of paracetamol is excreted within 24 hours). Excretion is significantly impaired with impaired renal excretory function, which can lead to the accumulation of acetaminophen and its metabolic products in the body. Ascorbic acid is actively absorbed in the small intestine. After oral administration C_max in blood plasma is reached after 4 hours. From the blood plasma it easily penetrates into white blood cells, platelets and almost all tissues. It undergoes biotransformation in the liver, excreted in the urine partially in unchanged form, partially in the form of metabolites.

Chlorpheniramine maleate is metabolized in the liver. T_½ is 8 hours. Chlorpheniramine maleate and its metabolites are excreted in the urine.

Indications

Assign to children aged 2 to 12 years with influenza, acute respiratory viral infections and colds to reduce body temperature, eliminate headaches, pain in muscles and joints, rhinorrhea, sneezing, lacrimation and other symptoms of inflammation of the mucous membrane of the upper respiratory tract and sinuses.

Application

Inside, regardless of the meal, after dissolving the contents of the package in a glass of hot (not boiling water) water. the recommended amount of water to dissolve the powder is usually the amount that the child drinks at one time (100-200 ml). a single dose for children aged 2–5 years is the contents of 1 packet, for children 6–12 years - 2 packets. if necessary, repeat the reception every 4-6 hours, but not more than 4 packets per day. the maximum period of use without consulting a doctor is 3 days. further use is possible only under the supervision of a doctor.

Children. Do not use in children under 2 years of age. It is necessary to consult a doctor before using the drug in children aged 2-5 years.

The maximum dose for children is up to 100 mg / kg / day, or 4000 mg / day.

Contraindications

Hypersensitivity to the components of the drug or other antihistamines; severe liver dysfunction (9 points on the Child-I drink scale) and / or kidney, alcoholism, congenital deficiency of glucose-6-phosphate dehydrogenase; congenital hyperbilirubinemia (including gilbert syndrome); hematopoietic disorders, blood diseases, severe leukopenia, anemia, tendency to thrombosis; severe cardiac conduction disorders, decompensated heart failure, bladder neck obstruction, pyloroduodenal obstruction; thrombosis, thrombophlebitis; severe forms of diabetes, angle-closure glaucoma; an ulcer of the stomach and duodenum in the acute stage; children under 2 years old.

Do not use simultaneously with MAO inhibitors and within 2 weeks after discontinuation of MAO inhibitors.

MAO inhibitors should not be used with antihistamines because of the possibility of additive CNS depression. They can lengthen and enhance the anticholinergic effect of antihistamines.

Side effects

In most cases, the drug is well tolerated.

The following side effects may occur:

• on the part of the blood system: anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, shortness of breath, heart pain), hemolytic anemia (in the case of a patient having a deficiency of glucose-6-phosphate dehydrogenase), thrombocytopenia, thrombocytosis, hyperprothrombinemia, erythrombocytocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrombocytosis, erythrocytocytopenia purpura, leukopenia, bruising or bleeding;
• from the respiratory system: bronchospasm in patients sensitive to acetylsalicylic acid or other NSAIDs;
• from the digestive tract: heartburn, nausea, vomiting, dry mouth, discomfort and pain in the epigastric region, hypersalivation, decreased appetite, constipation, diarrhea, flatulence;
• from the endocrine system: hypoglycemia up to hypoglycemic coma, damage to the insular apparatus of the pancreas (hyperglycemia, glucosuria) and impaired glycogen synthesis until diabetes mellitus;
• from the hepatobiliary system: impaired liver function, increased activity of liver enzymes, usually without the development of jaundice, hepatonecrosis (dose-dependent effect);
• from the immune system: hypersensitivity reactions (including allergic reactions), anaphylactic reactions and anaphylactic shock;
• from the nervous system: headache, dizziness, psychomotor agitation and disorientation, anxiety, fear, sleep disturbances, drowsiness, insomnia, confusion, coma, cramps, dyskinesia, behavior changes;
• from the cardiovascular system: tachycardia, reflex bradycardia, shortness of breath, heart pain, increased blood pressure, arrhythmia, myocardial dystrophy (dose-dependent effect with prolonged use);
• from the urinary system: renal colic and interstitial nephritis, urinary retention and difficulty urinating, aseptic pyuria, with prolonged use in high doses - damage to the glomerular apparatus of the kidneys, crystalluria, the formation of urate, cystine and / or oxalate calculi in the kidneys and urinary tract;
• on the part of the organ of vision: impaired accommodation, dry eyes, mydriasis, visual impairment, increased intraocular pressure;
• on the part of the metabolism: metabolic imbalance of zinc, copper, hypokalemia;
• on the part of the skin and subcutaneous tissues: itching, rash on the skin and mucous membranes (usually a generalized rash, erythema, urticaria), allergic and angioedema, acute generalized exanthematous pustulosis, local drug-induced dermatitis, erythema multiforme (including Stevens syndrome - toxic epidermal necrolysis (Lyells syndrome), including death.

special instructions

The simultaneous use of other drugs intended for the symptomatic treatment of colds and flu, medicines containing paracetamol should be avoided. do not exceed the specified dose and duration of treatment. simultaneous use with other drugs containing paracetamol can lead to an overdose. an overdose of paracetamol can cause liver failure, which can lead to the need for liver transplantation or death.

In patients with reduced glutathione levels, such as severe infections such as sepsis, paracetamol increases the risk of metabolic acidosis.Symptoms of metabolic acidosis are deep, rapid or difficult breathing, nausea, vomiting, loss of appetite. Seek medical attention immediately if these symptoms occur.

If symptoms persist, consult a doctor.

Long-term use of high doses can lead to damage to the liver and kidneys; a large number of drugs used simultaneously, alcoholism, alcoholic liver damage, sepsis or diabetes can increase the risk of hepatotoxicity of paracetamol (acetaminophen) in therapeutic doses.

It should be borne in mind that in patients with liver diseases, the risk of hepatotoxic effects of paracetamol is increased. It is necessary to consult a doctor regarding the possibility of using the drug in patients with impaired renal and hepatic function of mild to moderate severity.

This drug is not recommended for use simultaneously with sedatives or hypnotics.

Before using the drug, you should consult your doctor if the patient uses warfarin or similar drugs that have an anticoagulant effect.

Paracetamol may affect laboratory blood glucose and uric acid levels.

The drug should be prescribed by a doctor only after assessing the risk / benefit ratio in the following cases: severe hypertension, epilepsy, glaucoma, oxalaturia, impaired urination, urinary retention, enlarged prostate gland, asthma, bronchitis, thyrotoxicosis, glutathione deficiency.

The recommended dose and duration of treatment should not be exceeded. 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 picture of peripheral blood.

Cases of severe skin reactions have been reported very rarely. If skin redness, rashes, blisters, or peeling occur, discontinue use of paracetamol and seek medical attention immediately.

1 packet (1 dose) contains 11.6 g of sugar, which should be considered for patients with diabetes mellitus and patients on a diet with a low sugar content. Use with caution in patients with diabetes. The simultaneous administration of the drug with alkaline drink reduces the absorption of ascorbic acid, so you should not drink the powder with alkaline mineral water. Also, the absorption of ascorbic acid may be impaired with intestinal dyskinesia, enteritis and achilia.

This drug should not be used for fructose intolerance, glucose-galactose malabsorption syndrome or sucrose-isomaltase deficiency due to sucrose content. If you are intolerant of certain sugars, consult your doctor before taking this medication.

In case of high body temperature or prolonged fever that persists for 3 days against the background of the use of the drug, or if signs of superinfection appear, consult a doctor.

Ascorbic acid can change the results of laboratory tests (glucose, blood bilirubin, transaminase activity).

Do not take the drug with other remedies for the symptomatic treatment of colds and flu containing paracetamol or antihistamines. If symptoms persist, consult a doctor. If the headache becomes constant, you should also consult a doctor.

Chlorpheniramine can mask the symptoms of hypersensitivity reactions and affect the results of skin tests. Therefore, the use of the drug should be discontinued a few days before these manipulations.

Use during pregnancy and lactation. Do not use.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms.Due to the likelihood of drowsiness after the use of chlorpheniramine maleate, children should be restrained from activities requiring an increased concentration of attention for 4 hours after taking the drug.

Interactions

With simultaneous use with acetaminophen, the following types of interactions are possible:

• slowing the removal of antibiotics from the body;
• anticonvulsants (including phenytoin, barbiturates, carbamazepine), rifampicin and alcohol increase the hepato- and nephrotoxicity of acetaminophen;
• barbiturates reduce the antipyretic effect of acetaminophen;
• tetracycline increases the risk of developing anemia and methemoglobinemia caused by acetaminophen;
• with the simultaneous use of paracetamol with hepatotoxic drugs, the toxic effect of drugs on the liver increases; do not use simultaneously with alcohol;
• acetaminophen reduces the effectiveness of diuretics;
• the simultaneous use of high doses of acetaminophen with isoniazid or rifampicin increases the risk of hepatotoxic syndrome;
• increased effect of indirect anticoagulants with an increased risk of bleeding;
• the absorption rate of acetaminophen increases with the use of metoclopramide and domperidone and decreases with the use of cholestyramine;
• with simultaneous prolonged use with coumarin derivatives (eg warfarin) may enhance their effect with an increased risk of bleeding; patients using oral anticoagulants should consult a doctor, blood coagulation parameters should be monitored;
• taking paracetamol (acetaminophen) can affect blood glucose results by glucose oxidase peroxidase with abnormally high concentrations;
• taking paracetamol can affect the results of determining the level of urea in the blood by the phosphoric tungsten acid method;
• tropisetron and granisetron, type 5 hydroxytryptamine antagonists of the 3rd type can completely block the analgesic effect of paracetamol due to pharmacodynamic interaction;
• the simultaneous use of paracetamol and zidovudine tends to decrease the number of leukocytes (neutropenia), therefore, these drugs should not be used simultaneously, unless otherwise recommended by a doctor;
• the absorption of ascorbic acid is reduced with the simultaneous use of oral contraceptives, the use of fruit or vegetable juices, alkaline drinking;
• ascorbic acid when administered orally increases the absorption of penicillin, tetracycline, iron, increases the level of ethinyl estradiol, reduces the effectiveness of heparin and indirect anticoagulants, increases the risk of crystalluria in treatment with salicylates;
• the simultaneous intake of vitamin C and deferoxamine increases tissue toxicity of iron, especially in the heart muscle, which can lead to decompensation of the circulatory system; vitamin C can be taken only 2 hours after injection of deferoxamine;
• high doses of the drug reduce the effectiveness of tricyclic antidepressants, antipsychotics - phenothiazine derivatives, tubular reabsorption of amphetamine, disrupt kidney excretion of mexiletine;
• ascorbic acid increases the overall clearance of ethyl alcohol;
• quinoline drugs, calcium chloride, salicylates, corticosteroids with prolonged use reduce the reserves of ascorbic acid in the body.

Simultaneous use of Antiflu^® Kids with the following drugs - sleeping pills, sedatives, antipsychotics, tranquilizers - can significantly increase the inhibitory effect of chlorpheniramine maleate.

Chlorpheniramine enhances the anticholinergic effect of atropine, antispasmodics, tricyclic antidepressants, antiparkinsonian drugs.

MAO inhibitors should not be used with antihistamines because of the possibility of additive CNS depression. They can lengthen and enhance the anticholinergic effect of antihistamines.

Overdose

No overdose of antiflu® kids has been reported. symptoms of drug overdose consist of manifestations of intoxication of individual active substances.

In patients with risk factors, therapeutic doses of paracetamol can cause overdose symptoms while using certain drugs (see INTERACTIONS), for diseases that increase oxidative stress and deplete glutathione in the liver (prolonged fasting, sepsis, diabetes mellitus).

The most important effects of acute intoxication are hepatotoxicity - hepatocellular damage, which is due to the binding of active metabolites of paracetamol to hepatocyte proteins. In therapeutic doses, these metabolites bind to glutathione and form non-toxic conjugates. In the case of a significant overdose, the stocks of SH-group donors (contributing to the formation of glutathione) in the liver are depleted. This leads to the accumulation of toxic metabolites and necrosis of hepatocytes, followed by impaired liver function, which progresses up to the hepatic coma.

Overdose symptoms due to acetaminophen in the first 24 hours are pallor, nausea, vomiting, anorexia, general weakness, and abdominal pain (abdominal pain). The patients condition can improve within 24–48 hours, although symptoms may persist. When taken in high doses, psychomotor agitation or depression of the central nervous system, increased sweating, dizziness, and sleep disturbance may also occur.

Sometimes the urinary system showed nephrotoxicity, including renal colic, interstitial nephritis and acute renal failure with acute tubular necrosis, which can manifest severe pain in the lower back, hematuria, proteinuria and develop even in the absence of severe liver damage. In severe cases, liver damage (hepatocellular necrosis) and impairment of its function, which can progress to hepatic encephalopathy, hepatic coma, cerebral edema, and death, can be noted. Clinical signs of liver damage may not occur within 12–48 hours after an overdose. Liver size can increase rapidly. Impaired glucose metabolism, hypokalemia and metabolic acidosis (including lactic acidosis), increased activity of hepatic transaminases, increased levels of bilirubin and an increase in prothrombin index, hemorrhage may occur. The amount of urine decreases. Mild azotemia may be observed. In a child, liver damage can develop after applying 150 mg / kg of body weight. Frequent clinical manifestations that occur after 3-5 days include jaundice, fever, hemorrhagic diathesis, hypoglycemia, hepatic breath, liver failure.

The use of 5 g or more of paracetamol can lead to liver damage in patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. Johns wort or other drugs that induce liver enzymes, regular intake of excess ethanol; glutathione cachexia (digestive disorders) , cystic fibrosis, HIV infection, starvation, cachexia)).

Arrhythmia (cardiac arrhythmias) and pancreatitis were also noted. When taken in high doses from the central nervous system - disorientation.

With prolonged use in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia are possible.

Chronic intoxication includes various liver lesions.Data on chronic toxicity and especially nephrotoxicity of paracetamol are contradictory. With prolonged use, attention should be paid to the analysis of peripheral blood.

In case of an overdose of chlorpheniramine maleate, atropine-like symptoms can occur: mydriasis, photophobia, dry skin and mucous membranes, fever, tachycardia, intestinal atony, and redness of the face. Usually, symptoms of central nervous system excitement are noted first (psychomotor agitation, psychosis, hallucinations, tremors, impaired motor coordination, hyperreflexia, convulsions), and then depression, drowsiness, impaired consciousness, accompanied by impaired breathing and cardiovascular function (cardiac arrhythmias, extrasystole , decrease in heart rate, decrease in blood pressure before vascular failure and death). Emergency care for poisoning with antihistamines consists of symptomatic and supportive treatment, including mechanical ventilation.

Urgent care. The patient should be taken to the hospital immediately, even if there are no early symptoms of an overdose. Continuous monitoring of vital functions, laboratory data and the state of the cardiovascular system should be ensured. Symptoms may be limited by nausea and vomiting, or may not reflect the severity of an overdose or the risk of organ damage. Treatment with activated charcoal should be considered if an excessive dose of paracetamol was taken within 1 hour. The concentration of paracetamol in blood plasma should be measured 4 hours or later after administration (earlier concentrations are unreliable). Gastric lavage must be performed within 6 hours after a suspected overdose of acetaminophen. Hemodialysis and hemoperfusion contribute to the excretion of the substance. Cytotoxic effects can be reduced by administering SH-group donors (oral methionine or cysteamine or iv N-acetylcysteine) within 10 hours after an overdose, as they bind to active metabolites and promote detoxification. N-acetylcysteine ​​may be effective up to 48 hours after poisoning. The effectiveness of the antidote decreases sharply after this period.

Symptoms of an overdose of ascorbic acid. There is no evidence that this drug can be overdosed when taken in accordance with the recommendations. With a single use of excessive doses of the drug, nausea, vomiting, bloating and abdominal pain, itching, skin rash, increased irritability are possible. With prolonged use in high doses, inhibition of the insular apparatus of the pancreas is possible (it is necessary to control its function), the development of cystitis, the acceleration of the formation of calculi (urates, oxalates). The effects of an overdose of ascorbic acid can be attributed to severe hepatotoxicity due to an overdose of paracetamol.

High doses of ascorbic acid (3000 mg) can cause temporary osmotic diarrhea and gastrointestinal upsets.

Treatment: rinse the stomach, give the patient an alkaline drink, activated charcoal or other absorbents.

Storage conditions

In the original packaging at a temperature not exceeding 25 ° c.