AnviMax, cranberry 10 pcs.

Pharmacotherapeutic group: Acute respiratory infections and “colds” symptoms remedy.

The ATX code: R05X

Pharmacological properties

Pharmacodynamics

Combination drug, has antiviral, interferonogenic, antipyretic, analgesic, antihistamine and angioprotective action. Paracetamol has analgesic and antipyretic effects.

Ascorbic acid is involved in the regulation of redox processes, contributes to normal capillary permeability, blood coagulation, tissue regeneration, plays a positive role in the development of immune reactions.

Calcium gluconate as a source of calcium ions prevents development of increased permeability and fragility of blood vessels and causes hemorrhagic processes during influenza and acute respiratory viral infection (ARI).

Rimantadine has antiviral activity against influenza A virus. By blocking the M₂ channels of influenza A virus, it disrupts its ability to enter cells and release ribonucleoprotein, thereby inhibiting a crucial stage of viral replication. It induces production of interferon alpha and gamma. In influenza caused by B virus rimantadine has antitoxic effect.

Rutoside is an angioprotector. It reduces capillary permeability, swelling and inflammation, strengthens the vascular wall. Inhibits aggregation and increases the degree of deformation of red blood cells.

Loratadine is a blocker of H1-histamine receptors, prevents the development of tissue edema associated with the release of histamine.

Pharmacokinetics

Paracetamol. Absorption is high. Binding with plasma proteins is 15%. It penetrates through the blood-brain barrier. It is metabolized in the liver in three main ways: conjugation with glucuronides, conjugation with sulfates, oxidation by liver microsomal enzymes. In the latter case toxic intermediate metabolites are formed, which subsequently conjugate with glutathione and then with cysteine and mercapturic acid. The main cytochrome P450 isoenzymes for this metabolic pathway are CYP2E1 (predominantly), CYP1A2 and CYP3A4 (secondary role). In glutathione deficiency, these metabolites can cause damage and necrosis of hepatocytes. Additional metabolic pathways are hydroxylation to 3-hydroxyparacetamol and methoxylation to 3-methoxy-paracetamol, which are subsequently conjugated to glucuronides or sulfates. In adults, glucuronidation predominates. Conjugated metabolites of paracetamol (glucuronides, sulfates and conjugates with glutathione) have low pharmacological (including toxic) activity. Excreted by the kidneys as metabolites, mainly conjugates, only 3% unchanged. In elderly patients the drug clearance is decreased and the elimination half-life is increased.

Ascorbic acid is absorbed in the gastrointestinal tract (mainly in the jejunum). Binding with plasma proteins is 25%. Diseases of the gastrointestinal tract (gastric and duodenal ulcers, constipation or diarrhea, worm infestation, giardiasis), consumption of fresh fruit and vegetable juices, alkaline drinking reduce absorption of ascorbic acid in the intestine. Normal plasma concentration of ascorbic acid is approximately 10-20 µg/ml. Time of maximum plasma concentration after oral administration is 4 hours. It penetrates easily into leukocytes, platelets and then into all tissues; the highest concentration is reached in glandular organs, leukocytes, liver and eye lens; penetrates through placenta.

The concentration of ascorbic acid in leukocytes and platelets is higher than in erythrocytes and plasma. In deficiency states, the concentration in leukocytes decreases later and more slowly and is considered a better criterion for assessing deficiency than the concentration in plasma. It is metabolized mainly in the liver to deoxyascorbic acid and then to oxalic acetic acid and ascorbate-2-sulfate. It is excreted by the kidneys, through the intestines, with sweat unchanged and as metabolites. Smoking and use of ethanol accelerate the breakdown of ascorbic acid (conversion to inactive metabolites), dramatically reducing the body’s reserves. It is excreted by hemodialysis.

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 ergocalciferol, pH, dietary characteristics, and the presence of factors that can bind calcium ions. Absorption of calcium ions increases with calcium deficiency and with a diet low in calcium ions. About 20% is excreted by the kidneys, the rest (80%) by the intestine.

Rimantadine. After oral administration it is almost completely absorbed in the intestine. Absorption is slow. Binding to plasma proteins is about 40%. Distribution volume is 17-25 l/kg. Concentration in nasal secretion is 50% higher than in plasma. Metabolized in the liver. More than 90% is excreted by the kidneys within 72 hours, mainly as metabolites, 15% – unchanged. In chronic renal insufficiency half-life is 2 times longer. In patients with renal insufficiency and in the elderly the drug may accumulate in toxic concentrations if the dose is not adjusted in proportion to the decrease in creatinine clearance. Hemodialysis has little effect on rimantadine clearance.

Rutozide. Time of maximum concentration in blood plasma after oral administration is 1-9 hours. It is eliminated mainly in the bile and to a lesser extent by the kidneys. Half-life period is 10-25 hours.

Loratadine. Rapidly and completely absorbed in the gastrointestinal tract. The maximum concentration in the elderly increases by 50%. Binding with plasma proteins is 97%. It is metabolized in the liver with the formation of the active metabolite descarboethoxyloratadine with the participation of CYP3A4 cytochrome isoenzymes and to a lesser extent CYP2D6. It does not penetrate the blood-brain barrier. It is excreted by the kidneys and in bile. Pharmacokinetics is practically unchanged in patients with chronic renal insufficiency and in hemodialysis.

Indications

Composition

Active ingredients:

paracetamol – 360 mg,

ascorbic acid – 300 mg,

calcium gluconate monohydrate – 100 mg,

rimantadine hydrochloride – 50 mg,

rutoside trihydrate (in terms of rutoside) – 20 mg,

loratadine – 3 mg;

excipients: citric acid – 716 mg, sodium hydrocarbonate – 584 mg, sorbitol – 97.85 mg, macrogol (polyethylene glycol 6000) – 75 mg, isoleucine – 75 mg, Cranberry flavoring (Cranberry 924 food powder flavoring) – 75 mg, acesulfame potassium – 20 mg, aspartame – 20 mg, povidone (povidone K-30) – 3.75 mg, beet red dye (E 162) – 0.4 mg.

How to take, the dosage

Ingestion.

Dissolve the tablet in half a cup of boiled warm water. Use as soon as it dissolves. Stir the solution before drinking.

Adults: take 1 tablet 2-3 times a day after meals for 3-5 days (not more than 5 days) until the symptoms disappear.

If there is no improvement in the state of health, the drug should be stopped and a doctor should be consulted.

Interaction

Paracetamol reduces the effectiveness of uricosuric drugs. Concomitant use of paracetamol in high doses increases the effect of anticoagulant drugs. Inducers of microsomal oxidation in the liver (phenytoin, barbiturates, rifampicin, phenylbutazone, tricyclic antidepressants), ethanol and hepatotoxic drugs increase production of hydroxylated active metabolites, which causes the possibility of severe intoxication even with a small overdose. Simultaneous use with metoclopramide may increase the rate of absorption of paracetamol. Prolonged use of barbiturates reduces the effectiveness of paracetamol. Microsomal oxidation inhibitors reduce the risk of hepatotoxic effects.

Rimantadine increases the excitatory effect of caffeine. Cimetidine reduces the clearance of rimantadine by 18%.

Ascorbic acid increases the blood concentration of benzylpenicillin. Improves intestinal absorption of iron preparations (converts trivalent iron to divalent iron); may increase iron excretion when used concomitantly with deferoxamine. Increases the risk of crystalluria when treated with salicylates and short-acting sulfonamides, slows renal excretion of acids, increases excretion of drugs with an alkaline reaction (including alkaloids). Reduces the blood concentration of oral contraceptives. Increases the total clearance of ethanol, which in turn reduces the concentration of ascorbic acid in the body. When used concomitantly, reduces the chronotropic effect of isoprenaline. Barbiturates and primidone increase excretion of ascorbic acid with urine. Reduces the therapeutic effect of antipsychotic drugs (neuroleptics) – phenothiazine derivatives, tubal reabsorption of amphetamine and tricyclic antidepressants.

Loratadine. CYP3A4 and CYP2D6 inhibitors increase the blood concentration of loratadine.

Special Instructions

Duration of use – no more than 5 days.

Do not use if you have metastatic tumors.

Persons who are inclined to drink ethanol should consult a physician before starting treatment with the drug, because paracetamol may have a damaging effect on the liver.

Impact on ability to drive vehicles and other mechanisms requiring increased concentration

When taking this medicine, caution should be exercised when driving vehicles and engaging in other potentially dangerous activities requiring increased concentration and quick psychomotor reactions.

Synopsis

Circular flat-cylindrical tablets with rough surface of light pink to dark pink color with lighter and darker spots, beveled, with a characteristic odor. Allowed specks of greenish-yellow. Hydroscopic.

Contraindications

Hypersensitivity to one or more components included in the drug; gastrointestinal tract erosive ulcers in the acute phase; gastrointestinal bleeding; hemophilia; hemorrhagic diathesis; hypoprothrombinemia; portal hypertension; avitaminosis K; renal failure; pregnancy, breast-feeding period; Thyroid disease, acute kidney disease, liver disease (acute glomerulonephritis, acute pyelonephritis, acute hepatitis, or exacerbation of chronic diseases of these organs); chronic alcoholism; hypercalcemia, severe hypercalciuria, nephrourolithiasis, sarcoidosis, simultaneous use of cardiac glycosides (risk of arrhythmias); fructose intolerance; phenylketonuria.

Children under 18 years of age.

With caution

. Limitation of use in epilepsy, cerebral atherosclerosis, diabetes, glucose-6-phosphate dehydrogenase deficiency, hemochromatosis, sideroblastic anemia, thalassemia, hyperoxaluria, renal stone disease, dehydration, electrolyte disorders (risk of hypercalcemia), diarrhea, malabsorption syndrome, calcium nephrourolithiasis (history), hypercalciuria; concomitant or during the previous 2 weeks taking monoamine oxidase inhibitors, tricyclic antidepressants; concomitant use of drugs that may adversely affect the liver (e.g., inducers of microsomal liver enzymes). Caution should be exercised when treating patients with recurrent formation of urate kidney stones; advanced malignant diseases; bronchial asthma.

Elderly patients with arterial hypertension (increased risk of hemorrhagic stroke due to rimantadine in the drug).

Side effects

According to the components included.

Central nervous system disorders: increased excitability, drowsiness, tremor, hyperkinesia, dizziness, headache, “rushes” of blood to the face.

Digestive system disorders: lesion of the mucous membrane of the stomach and duodenum, dyspepsia, dry mucous membrane in the mouth, lack of appetite, bloating (flatulence), diarrhea (diarrhea).

Urinary system disorders: moderate pollakiuria.

Hematopoietic disorders: changes in blood counts. The control is necessary.

Allergic reactions: angioedema, anaphylactic shock, skin rash, itching, urticaria.

Skin disorders: Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome) and acute generalized exanthematous pustulosis.

Others: inhibition of pancreatic insular apparatus function (hyperglycemia, glucosuria).

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 immediately.

Overdose

Symptoms: during the first 24 hours after ingestion – pale skin, nausea, diarrhea, vomiting, pain in the epigastric region; impaired glucose metabolism, metabolic acidosis (including lactoacidosis), hypokalemia, tachycardia, arrhythmia, headache, exacerbation of associated chronic diseases. Symptoms of liver dysfunction may appear 12-48 hours after overdose. In severe overdose – hepatic failure with progressive encephalopathy, coma; acute renal failure with tubular necrosis (including in the absence of severe liver damage).

The threshold for overdose may be lowered in elderly patients, in patients taking certain drugs (e.g., inducers of microsomal liver enzymes), alcohol, or those suffering from exhaustion.

Treatment: administration of SH-group donators and precursors of glutathione synthesis – methionine within 8-9 hours after overdose and acetylcysteine – within 8 hours. Gastric lavage, symptomatic therapy. The need for additional therapeutic measures (further administration of methionine, acetylcysteine) is determined depending on the concentration of paracetamol in the blood, as well as on the time elapsed after its administration.

Pregnancy use