ANDIPAL AVEXIMA TAB. No. 10

Side effects

The frequency of these side effects is indicated in accordance with the WHO classification: very often - more than 10%;
often – more than 1% and less than 10%; infrequently – more than 0.1% and less than 1%; rarely - more than 0.01% and less than 0.1%; very rarely - less than 0.01%, including isolated cases;

frequency unknown – based on the available data, it was not possible to establish the frequency of occurrence.

For Andipal: To date, no side effects have been reported with this combination. The incidence of the following possible side effects is unknown.

From the central nervous system: drowsiness, decreased speed of psychomotor reactions. From the digestive system: nausea, constipation.

From the cardiovascular system: arterial hypotension. Allergic reactions. With long-term use: leukopenia, agranulocytosis, impaired liver and kidney function.

For Metamizole sodium: On the skin: uncommon - persistent drug rash; rarely - rash (for example, maculopapular); very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the urinary system: very rarely - acute renal dysfunction, which in very rare cases can lead to proteinuria, oligo- or anuria and acute renal failure, acute interstitial nephritis.

From the hematopoietic organs: rarely – leukopenia; very rarely - agranulocytosis, including fatal cases, thrombocytopenia;

frequency unknown - aplastic anemia, pancytopenia, including fatal cases.

These reactions can occur even if metamizole sodium has not previously caused complications. There are a number of signs of an increased risk of agranulocytosis if metamizole sodium is used for more than one week. This reaction is dose-independent and can occur at any time during treatment.

It is manifested by high fever, chills, sore throat, pain when swallowing, inflammation of the mucous membranes of the mouth, nose, throat, genital and anal area. However, when antibiotics are used, these phenomena may be mild.

There is a slight enlargement of the lymph nodes and spleen or no enlargement at all. The erythrocyte sedimentation rate increases significantly, the content of granulocytes is sharply reduced or they are not detected. As a rule, but not always, normal levels of hemoglobin, red blood cells and platelets are maintained.

Treatment tactics involve immediate discontinuation of the drug, i.e. the drug should be discontinued immediately, without waiting for laboratory results, if there is an unexpected deterioration in general condition, the fever does not subside, or new or painful ulcerations appear on the mucous membranes, especially in the mouth, nose or throat.

If pancytopenia occurs, the drug should be discontinued immediately and a complete blood count should be monitored until its values return to normal.

From the cardiovascular system: infrequently - an isolated decrease in blood pressure (possibly pharmacologically caused and not accompanied by other manifestations of anaphylactic/anaphylactoid reactions). The decrease in blood pressure can be pronounced.

During fever, a dose-dependent sharp decrease in blood pressure without other signs of a hypersensitivity reaction is also possible.

Allergic reactions: rarely - anaphylactoid or anaphylactic reactions; very rarely - analgesic bronchial asthma. In patients with analgesic bronchial asthma, intolerance usually manifests itself as attacks of bronchial asthma; frequency unknown: anaphylactic shock.

These reactions are especially typical with parenteral administration of metamizole sodium and can be severe and life-threatening, in some cases leading to death.

These reactions can occur even if metamizole sodium has not previously caused complications. These reactions may occur during administration or immediately after ingestion, or develop several hours later.

However, they predominantly occur within the first hour after application. In milder cases, they manifest as rashes on the skin and mucous membranes (eg, itching, burning, redness, blistering and swelling), shortness of breath and, less commonly, gastrointestinal disorders.

In severe cases, these mild reactions can develop into generalized urticaria, severe angioedema (including of the larynx), severe bronchospasm, cardiac arrhythmias, arterial hypotension (in some cases preceded by increased blood pressure, shock.

In this regard, at the first signs of skin reactions, the drug should be discontinued.

Other: frequency unknown: red coloration of urine has been reported, which may be due to the presence of low concentrations of rubazonic acid (a metabolite of metamizole sodium).

For Phenobarbital:

From the central nervous system: frequency unknown - asthenia, dizziness, general weakness, ataxia, nystagmus, paradoxical reaction (especially in elderly and weakened patients - agitation), hallucinations, depression, nightmares, syncope.

From the digestive system: frequency unknown - vomiting, with prolonged use, liver dysfunction.

From the hematopoietic organs: frequency unknown - agranulocytosis, megaloblastic anemia, thrombocytopenia.

Allergic reactions: frequency unknown - skin rash, urticaria, swelling of the eyelids, face and lips, difficulty breathing, rarely - exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome).

Other: frequency unknown - with long-term use, drug dependence.

INSTRUCTIONS for the use of the medicinal product for medical use ANDIPAL AVEXIMA

For Bendazole:

The listed effects appear when used in large doses. When the dose is reduced or the drug is discontinued, these side effects quickly disappear.

From the central nervous system: frequency unknown – dizziness, headache.

From the skin: frequency unknown - increased sweating.

From the digestive system: frequency unknown - nausea.

For Papaverine hydrochloride:

From the central nervous system: often – drowsiness.

From the skin: often - skin rash (usually erythematous, urticaria), infrequently - itching, rarely - increased sweating.

From the digestive system: often – nausea, constipation, infrequently – increased activity of “liver” transaminases.

From the cardiovascular system: often - decreased blood pressure, infrequently - ventricular extrasystole.

From the hematopoietic organs: very rarely - eosinophilia.

Andipal Avexima tablets No. 10

Compound

Active ingredients: metamizole sodium (analgin) – 250 mg, phenobarbital – 20 mg, bendazole (dibazole) – 20 mg, papaverine hydrochloride – 20 mg.
Excipients: potato starch – 46 mg, talc – 7 mg, stearic acid – 3 mg, calcium stearate – 4 mg.

Pharmacokinetics

Metamizole sodium: well and quickly absorbed from the gastrointestinal tract. It is hydrolyzed in the intestinal wall to form an active metabolite; unchanged metamizole sodium is absent in the blood (only after intravenous administration its insignificant concentration is detected in the plasma). The connection of the active metabolite with proteins is 50-60%. Metabolized in the liver, excreted by the kidneys. In therapeutic doses it penetrates into mother's milk.

Phenobarbital: when taken orally, phenobarbital is completely, but relatively slowly absorbed. The maximum concentration in the blood is observed 1-2 hours after administration. About 50% binds to plasma proteins. The drug is evenly distributed in different organs and tissues; lower concentrations are found in brain tissue. The half-life in adults is 2-4 days. It is released from the body slowly, which creates the preconditions for cumulation. Metabolized by microsomal liver enzymes. It is excreted by the kidneys in the form of inactive metabolites, 25-50% unchanged.

Bendazole: bioavailability is about 80%; the products of bendazole biotransformation in the blood are two conjugates formed due to methylation and carboethoxylation of the imino group of the imidazole ring of bendazole: 1-methyl-2-benzylbenzimidazole and 1-carboethoxy-2-benzylbenzimidazole. Bendazole metabolites are excreted in the urine.

Papaverine hydrochloride: bioavailability on average - 54%. Communication with plasma proteins – 90%. It is well distributed and penetrates histohematic barriers. Metabolized in the liver. The half-life is 0.5-2 hours (can be extended to 24 hours). Excreted by the kidneys in the form of metabolites. It is completely removed from the blood during hemodialysis.

Indications for use

Pain syndrome (mild or moderate) associated with spasm of peripheral arteries, smooth muscles of the gastrointestinal tract and genitourinary system, cerebral vessels, with increased blood pressure.

Contraindications

Hypersensitivity (including to pyrazolone derivatives); inhibition of bone marrow hematopoiesis; severe liver and/or kidney failure;
deficiency of glucose-6-phosphate dehydrogenase; children under 8 years of age, pregnancy, lactation, tachyarrhythmias, stable angina III-IV
functional class, unstable angina, spontaneous angina, collapse, decompensated chronic heart failure;
angle-closure glaucoma; prostatic hyperplasia; intestinal obstruction, megacolon, respiratory diseases,
accompanied by obstructive syndrome; bronchial asthma provoked by taking acetylsalicylic acid,
salicylates and other non-steroidal anti-inflammatory drugs; disturbance of atrioventricular conduction;
coma; respiratory depression;
elderly age; diseases accompanied by increased muscle tone, convulsive syndrome, porphyria (including a history),
myasthenia gravis, alcohol or drug addiction.

With caution: Arterial hypotension, peripheral blood diseases, liver failure.

Directions for use and doses

Orally, adults and children over 8 years old, 1 tablet 2-3 times a day, no more than 5 days. Do not use without consulting a doctor for more than 3 days.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Best before date

2 years 6 months. The drug should not be used after the expiration date.

special instructions

Do not use without consulting a doctor for more than 3 days.

If there is no effect within 3 days, you should stop taking the drug and consult a doctor. Children and adolescents under 18 years of age should use the drug only as prescribed by a doctor.

Elderly and debilitated patients: Elderly patients need to reduce the dose as they may have reduced excretion of metamizole sodium metabolites.

Chronic kidney disease (CKD) and impaired creatinine clearance (CC): Patients with CKD and impaired creatinine clearance should have their dose reduced as they may have reduced excretion of metamizole sodium metabolites.

Hepatic impairment: Because the rate of elimination of the drug is reduced in patients with impaired liver function, repeated use of high doses should be avoided. For short-term use, no dose reduction is required. There is no experience of long-term use.

Anaphylactic/anaphylactoid reactions: an increased risk of developing hypersensitivity reactions to metamizole sodium is caused by the following conditions - analgesic bronchial asthma or intolerance to analgesics (urticaria-angioedema type); bronchial asthma, especially accompanied by rhinosinusitis and nasal polyposis; chronic urticaria; intolerance to dyes (for example, tartrazine) or preservatives (for example, benzoates); alcohol intolerance, against the background of which, even when taking a small amount of alcoholic beverages, patients experience sneezing, lacrimation and severe redness of the face. Alcohol intolerance may indicate previously unidentified analgesic bronchial asthma. Anaphylactic shock may occur in susceptible patients, so special caution should be exercised in patients with asthma or atopy.

Severe skin reactions: Life-threatening skin reactions, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been described with the use of metamizole sodium. If signs of SJS or TEN appear (such as a progressive skin rash, often accompanied by blistering or ulceration of the mucous membrane), treatment should be stopped immediately and never restarted.

Isolated hypotensive reactions:

Metamizole sodium may cause hypotensive reactions (see section "Side effects"). These reactions may be dose-dependent. They are more typical for parenteral rather than oral administration. The risk of such reactions is also increased in: pre-existing hypotension, decreased circulating blood volume or dehydration, unstable hemodynamics or acute circulatory disorders (for example, in patients with myocardial infarction or trauma), in patients with high fever. In this regard, such patients should undergo detailed diagnostics and be closely monitored. Preventive measures (eg, cardiovascular resuscitation) may be necessary to reduce the risk of hypotensive reactions. In patients in whom lowering blood pressure should be avoided at all costs (for example, with severe ischemic heart disease or significant cerebral artery stenosis), metamizole sodium should only be used with careful monitoring of hemodynamic parameters.

Abdominal pain: it is unacceptable to use the drug to relieve acute abdominal pain (until their cause is identified).

Description

Analgesic (non-narcotic analgesic + antispasmodic + barbiturate).

Pharmacodynamics

Combined drug. The combination of the components of the drug leads to a mutual enhancement of their pharmacological action.

Pharmacodynamics

Metamizole sodium is a pyrazolone derivative that has analgesic, antipyretic and antispasmodic effects. According to research results, metamizole and its active metabolite (4N-methylaminoantipyrine) have a central and peripheral mechanism of action. Non-selectively inhibits cyclooxygenase and reduces the formation of prostaglandins from arachidonic acid.

Phenobarbital belongs to the group of barbiturates. The benzodiazepine-γ-aminobutyric acid (GABA) receptor complex interacts with the barbiturate site, thereby increasing the sensitivity of GABA receptors to GABA, leading to the opening of chloride channels, which increases their entry into the cell and leads to hyperpolarization. Suppresses the sensory zones of the cerebral cortex, reduces motor activity, and inhibits cerebral functions, including the respiratory center. Reduces the tone of the smooth muscles of the gastrointestinal tract. In small doses it has a sedative effect and enhances the effect of other components.

Bendazole (dibazole): vasodilator; has a vasodilating effect, stimulates the function of the spinal cord. It has a direct antispasmodic effect on the smooth muscles of blood vessels and internal organs. Facilitates synaptic transmission in the spinal cord.

Papaverine hydrochloride is an antispasmodic, has a hypotensive effect, reduces tone and relaxes the smooth muscles of internal organs and blood vessels.

Side effects

The frequency of these side effects is indicated in accordance with the WHO classification: very often - more than 10%; often – more than 1% and less than 10%;

infrequently – more than 0.1% and less than 1%; rarely - more than 0.01% and less than 0.1%; very rarely - less than 0.01%, including isolated cases;

frequency unknown – based on the available data, it was not possible to establish the frequency of occurrence.

For Andipal: To date, no side effects have been reported with this combination. The incidence of the following possible side effects is unknown.

From the central nervous system: drowsiness, decreased speed of psychomotor reactions. From the digestive system: nausea, constipation.

From the cardiovascular system: arterial hypotension. Allergic reactions. With long-term use: leukopenia, agranulocytosis, impaired liver and kidney function.

For Metamizole sodium: on the skin: infrequently - persistent drug rash; rarely - rash (for example, maculopapular); very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis.