AnviMax, 20 pcs.

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

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 – 15%. It penetrates through the blood-brain barrier. 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-methoxyparacetamol, 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 decreases and the elimination half-life increases.

The maximum concentration (C_max) of paracetamol in plasma is reached after 1.20±0.72 hours when using capsules and is 5.01±1.70 µg/ml; half-life (T_1/2) is 3.04±1.01 hours.

Ascorbic acid is absorbed in the gastrointestinal tract (mainly in the jejunum). The binding to plasma proteins is 25%. Diseases of the gastrointestinal tract (gastric and 12 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. The plasma concentration of ascorbic acid in normal blood is approximately 10-20 µg/ml. Time of maximum concentration in blood plasma after oral intake 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; it penetrates through the 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 further to oxalic acetic acid and ascorbate-2-sulfate. It is excreted by kidneys, intestines and sweat glands 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 failure T_1/2 is increased by 2 times. In persons with renal insufficiency and in the elderly it 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.

The C_max of rimantadine in plasma is reached when capsules are used after 4.53±2.52 hours and is 68.2±26.6 ng/mL, T_1/2 is 30.51±9.83 hours.

Rutoside. Time of maximum concentration in blood plasma after oral administration – 1-9 hours. It is excreted mainly with the bile and to a lesser extent by the kidneys. T_1/2 is 10-25 h.

Loratadine. Rapidly and completely absorbed in the gastrointestinal tract. The maximum concentration in the elderly is increased 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 cytochrome isoenzymes CYP3A4 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.

The C_max of loratadine in plasma is reached after 2.92±1.31 hours and is 2.36±1.53 ng/mL, T_1/2 is 12.36±6.84 hours.

Indications

Active ingredient

Composition

Capsule P.

Active ingredient: paracetamol – 360 mg;

Excipients: pregelatinized starch – 9 mg, colloidal silica – 3 mg, lactose monohydrate – 1.2 mg, magnesium stearate – 3.8 mg, polysorbate 80 – 3 mg.

The contents of hard gelatin capsule: gelatin – 94.795 mg, proprietary blue dye (E 131) or brilliant blue dye (E 133) – 0.265 mg, titanium dioxide (E 171) – 1.94 mg.

Capsule P.

Active ingredients: 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: potato starch – 2.2 mg, magnesium stearate – 4.8 mg.

Solid gelatin capsule ingredients: gelatin – 94.064 mg, iron oxide yellow dye (E 172) – 0.97 mg, iron oxide red dye (E 172) – 0.485 mg, crimson dye [Ponceau 4R] (E 124) – 0.511 mg, titanium dioxide (E 171) – 0.97 mg.

How to take, the dosage

Ingestion.

Adults: 1 capsule P in blue and 1 capsule P in red (single dose) 2-3 times a day after meals with water. The interval between doses of the drug is 4-6 hours. The course of therapy until the disappearance of symptoms. Anvimax® should not be taken more than 5 days. If there is no relief of symptoms within 3 days after the start of the drug, it is necessary to consult a doctor.

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.

Laboratory monitoring of blood parameters should be performed.

Do not use if you have metastatic tumors.

Persons who are prone to drink ethanol should talk to their doctor before starting treatment with the drug, because paracetamol may have a damaging effect on the liver.

Impact on ability to drive and operate vehicles and other activities requiring increased concentration

With regard to the possible development of side effects (dizziness, somnolence), during the treatment period it is not recommended to drive vehicles and perform other activities requiring increased concentration and high speed of psychomotor reactions.

Synopsis

P hard gelatin capsules #0 of blue color. The contents of capsules – a mixture of powder and granules of white or white with a creamy or pinkish hue, some lumps are possible.

P hard gelatin capsules #0 of red color. The contents of the capsules – a mixture of powder and granules from yellow to yellow with a greenish tinge and white, some lumps are possible.

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, marked hypercalciuria, nephrourolithiasis, sarcoidosis, concomitant use of cardiac glycosides (risk of arrhythmias); lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Children under 18 years of age.

With caution

. Limitation of use in epilepsy, cerebral atherosclerosis, diabetes mellitus, glucose-6-phosphate dehydrogenase deficiency, hemochromatosis, sideroblastic anemia, thalassemia, hyperoxaluria, renal stone disease, dehydration, electrolyte disorders (risk of hypercalcemia), diarrhea, malabsorption syndrome, calcium nephrourolithiasis (in anamnesis), hypercalciuria.

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

Side effects

Possible unwanted adverse reactions are listed according to the constituent components.

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: moderate pollakiuria.

Hematopoietic organs: changes in blood counts.

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).

Post-registration experience

In the course of using AnviMax® have been described in cases of angioedema, preconsciousness, fever, decreased blood pressure, urticaria, pruritus, erythema, hearing loss, and sore throat.

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, 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).

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

Similarities