Belalgin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BELLALGIN (BELLALGIN)

Composition:

Active substances: 1 tablet contains metamizole sodium, calculated as anhydrous substance – 250 mg, benzocaine – 250 mg, sodium bicarbonate – 100 mg, dry extract of belladonna ((4.8–5.2):1) (Belladonnae extractum spissum) (extraction solvent: 20% (v/v) ethanol) – 15 mg;

Excipients: microcrystalline cellulose, mannitol (E421), sodium croscarmellose, magnesium stearate, colloidal anhydrous silicon dioxide.

Pharmaceutical form. Tablets.

Main physicochemical properties: round-shaped tablets with a flat surface, light brown to brownish-yellow in color with specks, beveled edges (chamfered) and a score line.

Pharmacotherapeutic group. Drugs used in functional gastrointestinal disorders. Spasmolytics in combination with analgesics. Alkaloids of belladonna in combination with analgesics. ATC Code A03DB.

Pharmacological properties.

Due to the M-cholinolytic effect of belladonna extract, the drug reduces the tone and motor activity of smooth muscles of the gastrointestinal tract and other organs, and decreases secretion of exocrine glands. The analgesic effect of the drug is due to the actions of sodium metamizole and the local anesthetic benzocaine. Sodium bicarbonate neutralizes free hydrochloric acid in the stomach.

Clinical characteristics.

Indications.

• Functional disorders of the gastrointestinal tract (abdominal pain of functional origin).
• Cholelithiasis.

Contraindications.

• Hypersensitivity to belladonna, benzocaine, other amide-type anesthetics, sodium metamizole, and other pyrazolone derivatives, or to any component of the drug.
• Cardiovascular diseases in which an increase in heart rate may be undesirable: atrial fibrillation, tachycardia, chronic heart failure, ischemic heart disease, mitral stenosis, severe arterial hypertension.
• Glaucoma.
• Urinary retention or predisposition to it, including prostatic adenoma with impaired urine flow.
• Myasthenia gravis.
• Gastrointestinal disorders associated with obstruction.
• Hyperthermic syndrome.
• Thyrotoxicosis.
• Acute bleeding.
• Changes in peripheral blood composition: agranulocytosis caused by metamizole, other pyrazolones, or pyrazolidines in history, leukopenia.
• Blood disorders: anemia of any etiology, cytostatic or infectious neutropenia.
• Severe impairment of liver and/or kidney function (porphyrin metabolism).
• Congenital glucose-6-phosphate dehydrogenase deficiency.
• Bronchial asthma.
• Suspicion of acute surgical pathology.
• Bone marrow dysfunction or hematopoietic system disorders.

Interaction with other medicinal products and other types of interactions.

If the patient is taking any other medicinal products, it is essential to inform the physician.

Interactions possibly caused by sodium metamizole

• X-ray contrast agents, colloidal plasma substitutes, penicillin – should not be used during treatment with sodium metamizole.
• Chlorpromazine or other phenothiazine derivatives – may cause pronounced hypothermia.
• Oral hypoglycemic agents (including sulfonylurea derivatives), indirect anticoagulants, glucocorticosteroids, indomethacin – sodium metamizole increases the activity of these drugs by displacing them from protein binding.
• Phenylbutazone, glutethimide, barbiturates, and other inducers of hepatic microsomal enzymes – reduce the efficacy of sodium metamizole.
• Non-narcotic analgesics, tricyclic antidepressants, hormonal contraceptives, and allopurinol – may enhance the toxicity of sodium metamizole.
• Non-steroidal anti-inflammatory drugs (NSAIDs) – their analgesic and antipyretic effects are potentiated, and the risk of additive adverse effects increases.
• Sedatives and tranquilizers (diazepam, trioxazine, valocordin), codeine, anaprilin, H2-histamine receptor blockers, propranolol – enhance the analgesic effect of sodium metamizole.
• Sarcolysin (chlormethine), mercaptopurine (mercazole), thiimazole, drugs suppressing bone marrow activity, including gold compounds – increased risk of hematotoxicity, including development of leukopenia.
• Cyclosporine – decreased plasma concentration of cyclosporine.
• Diuretics (furosemide) – possible reduction of diuretic effect.
• Methotrexate – high doses of metamizole may lead to increased methotrexate plasma concentration and enhanced toxic effects (on the gastrointestinal tract and hematopoietic system).
• Sodium metamizole enhances the sedative effect of ethanol.
• Metamizole may induce metabolic enzymes, including CYP2B6 and CYP3A4.
• Concurrent use of metamizole with bupropion, efavirenz, methadone, valproate, cyclosporine, tacrolimus, and sertraline may reduce plasma concentrations of these drugs, potentially decreasing their clinical efficacy. Therefore, caution is recommended when using metamizole concomitantly; monitoring of clinical response and/or drug levels may be necessary.

Interactions possibly caused by belladonna extract and benzocaine

The effect of the drug may be enhanced when used concurrently with other agents having antimuscarinic effects.

• Antiparkinsonian agents (amantadine), M-cholinoblockers, antiarrhythmic anticholinergic drugs (including quinidine, disopyramide), spasmolytics, tricyclic antidepressants, glutethimide – anticholinergic effects of Bellalgin are enhanced.
• Opioid analgesics and drugs that suppress the central nervous system (including phenothiazines) – dangerous CNS depression may occur; duration and depth of action of narcotics may be reduced, and analgesic effect of opioids may be diminished.
• Butyrophenones (haloperidol), organic nitrates – intraocular pressure may increase.
• Systemic corticosteroids – reduced corticosteroid effect and possible increase in intraocular pressure.
• Pilocarpine – its effect in glaucoma treatment is reduced.
• Furosemide – orthostatic hypotension may occur.
• Reserpine, guanethidine, antacids, ascorbic acid, attapulgite – reduced effect of Bellalgin.
• Levodopa – systemic levodopa concentrations are reduced; therefore, dosage adjustment may be required.
• Certain antihistamines (including meclizine) – antihistaminic effect is enhanced.
• Beta-adrenergic blockers – their effect is reduced.
• Hormonal contraceptives – contraceptive effect is reduced.
• Monoamine oxidase inhibitors (MAOIs), including non-selective inhibitors of neuronal reuptake of monoamines – sedative effect is enhanced; cardiac arrhythmias may occur.
• Non-steroidal anti-inflammatory drugs, griseofulvin, digoxin, doxycycline, metoclopramide, metronidazole – reduced efficacy of these drugs.
• Ketoconazole – increased gastric pH due to Bellalgin reduces ketoconazole absorption; therefore, Bellalgin should be taken no earlier than 2 hours after ketoconazole.
• Sulfonamides – antibacterial activity is reduced.
• Indapamide, nizatidine – their effect is enhanced.
• Potassium chloride – possible damage to gastrointestinal mucosa.
• Inhibition of peristalsis by the drug may alter the absorption of other medicinal products.
• Dimenhydrinate, diprazine – Bellalgin's effect is enhanced.
• Spironolactone, minoxidil – their effect is reduced.
• Penicillins – effect of both drugs is enhanced.

Special precautions for use.

Before starting treatment with Belalgin, consult a physician.

Agranulocytosis

Treatment with metamizole may cause agranulocytosis, sometimes with fatal outcome (see section "Adverse reactions"). This condition may occur even if previous use of metamizole did not lead to complications.

Agranulocytosis caused by metamizole is an idiosyncratic adverse reaction. This reaction may occur independently of the drug dose and at any time during treatment, as well as shortly after its discontinuation.

Patients should be advised to discontinue metamizole and seek immediate medical attention if any symptoms suggestive of agranulocytosis occur (e.g., fever, chills, sore throat, and painful mucosal lesions, particularly in the mouth, nose, and throat, as well as in the genital or anal areas).

If metamizole is used for fever, some symptoms of developing agranulocytosis may remain unnoticed. Similarly, these symptoms may be overlooked in patients receiving antibiotic therapy.

In the event of signs and symptoms suggestive of agranulocytosis, a complete blood count (particularly differential leukocyte count) should be performed immediately, and treatment should be discontinued pending test results. If agranulocytosis is confirmed, treatment should not be resumed (see section "Contraindications").

Drug-induced liver injury

Cases of acute hepatitis, predominantly hepatocellular in nature, have been reported in patients receiving metamizole, occurring from several days to several months after initiation of treatment. Symptoms included elevated serum liver enzymes with or without jaundice, often in combination with other hypersensitivity reactions (e.g., skin rash, blood disorders, fever, eosinophilia) or signs of autoimmune hepatitis. Most patients recovered after discontinuation of metamizole; however, in isolated cases, progression to acute liver failure requiring liver transplantation has been reported. The mechanism of metamizole-induced liver injury is not fully understood, but data suggest an immune-allergic mechanism. Patients should be informed of the need to seek medical advice if symptoms indicating liver injury occur. In such cases, metamizole should be discontinued and liver function assessed. Metamizole should not be re-administered to patients who have experienced liver injury during previous treatment with metamizole, unless other causes of liver injury have been ruled out.

If persistent or worsening abdominal pain of unknown origin occurs, accompanied by symptoms such as fever, nausea, vomiting, changes in intestinal peristalsis, decreased blood pressure, loss of consciousness, or blood in the stool, medical consultation is required.

The recommended doses of the drug should not be exceeded. The lowest effective dose should be used.

The drug should not be used to relieve acute abdominal pain (before the cause is established).

Alcohol consumption should be avoided during use of the drug.

Use with caution in patients:

• with marked arterial hypotension or cardiovascular insufficiency;
• with existing allergic conditions (including pollinosis) or a history thereof due to increased risk of hypersensitivity reactions;
• with prostatic hyperplasia without urinary tract obstruction;
• with Down's syndrome, cerebral palsy, or brain injury;
• with a history of kidney disease (pyelonephritis, glomerulonephritis), or with hepatic or renal insufficiency;
• with reflux esophagitis, hiatal hernia associated with reflux esophagitis;
• with inflammatory bowel diseases, including ulcerative colitis and Crohn's disease;
• with megacolon;
• with xerostomia (dry mouth);
• in elderly patients – may lead to increased frequency of adverse reactions, particularly gastrointestinal;
• with chronic lung diseases associated with low production of difficult-to-expectorate sputum, especially in debilitated patients;
• with chronic lung diseases without reversible obstruction;
• with autonomic (vegetative) neuropathy;
• during cytostatic therapy;
• with chronic alcoholism;
• with hyperthermia, especially in elderly or debilitated patients – hyperthermia may be exacerbated;
• in high ambient temperature (risk of heat stroke due to suppression of sweat gland activity).

In patients with undiagnosed and therefore untreated angle-closure glaucoma, use of anticholinergic agents such as belladonna alkaloids may lead to increased intraocular pressure. Therefore, if eye pain, redness of the eyes, accompanied by worsening or loss of vision occurs, the patient should consult an ophthalmologist.

There is a risk of methemoglobinemia with drugs containing benzocaine, primarily in patients with congenital defects such as glucose-6-phosphate dehydrogenase deficiency, NADH-methemoglobin reductase deficiency, pyruvate kinase deficiency, or hemoglobin M. Symptoms such as cyanosis of the skin, lips, and nail beds, headache, dizziness, dyspnea, weakness, and tachycardia may indicate potentially life-threatening methemoglobinemia requiring immediate medical intervention.

Belladonna alkaloids may affect the results of the following laboratory tests:

• gastric acidity test (may antagonize the activity of pentagastrin and histamine; drug intake should be discontinued 24 hours before the test);
• radionuclide gastric emptying study (may delay gastric emptying);
• phenolsulfonphthalein urinary secretion test (may delay excretion of phenolsulfonphthalein in urine).

The drug contains benzocaine, which may cause a positive doping test result in athletes.

Regular long-term use of the drug is not recommended due to the myelotoxicity of metamizole; with prolonged use (more than 7 days), qualitative and quantitative composition of peripheral blood, especially the leukocyte formula, should be monitored.

Agranulocytosis may develop during treatment; therefore, if unexplained fever, chills, sore throat, dysphagia, stomatitis, gingival bleeding, pallor of the skin, asthenia, or inflammation of external genital organs and anus occur, the drug should be discontinued immediately.

The drug should be discontinued if skin or mucous membrane rashes appear. In such cases, immediate medical consultation is required.

Red discoloration of urine may occur during drug intake due to excretion of a metabolite of sodium metamizole; this is not clinically significant.

The drug should not be used beyond the recommended duration without consulting a physician.

If symptoms of illness do not begin to subside, or if the patient's condition worsens, or if adverse effects occur, drug intake should be discontinued and medical advice sought regarding further use.

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy.

If use of the drug is necessary, breastfeeding should be discontinued.

Effect on ability to drive vehicles or operate machinery.

The drug is not recommended for patients whose activities require high attention concentration and rapid psychomotor reactions.

Dosage and Administration.

Belalgin is intended for symptomatic short-term use; therefore, the dose and duration of treatment should be individually selected.

For oral administration in adults: 1 tablet as needed for pain. Maximum daily dose – 10 tablets.

Children.

There are no clinical data on the efficacy and safety of use in children; therefore, the drug should not be administered to patients under 18 years of age.

Overdose.

Belladonna extract.

Symptoms: intensification of adverse reactions, nausea, vomiting, tachycardia, decreased blood pressure, accommodation disturbances, psychomotor agitation, irritability, tremor, seizures, insomnia, drowsiness, hallucinations, delirium, hyperthermia, central nervous system depression, respiratory and vasomotor center depression, urinary retention.

Sodium metamizole.

Symptoms: hypothermia, pronounced decrease in blood pressure, palpitations, dyspnea, dysphagia, tinnitus, nausea, vomiting, epigastric pain, oliguria, anuria, tachycardia, weakness, drowsiness, delirium, impaired consciousness, convulsive syndrome; acute agranulocytosis, hemorrhagic syndrome, acute renal and hepatic failure, respiratory muscle paralysis may develop.

Benzocaine.

Symptoms: drowsiness, restlessness, excitation, and in severe cases – seizures due to systemic absorption. There have been reports that administration of benzocaine-containing products may cause methemoglobinemia. Symptoms such as cyanosis of the skin, lips, and nail beds, headache, dizziness, dyspnea, weakness, and tachycardia may indicate potentially life-threatening methemoglobinemia requiring immediate medical intervention.

Treatment: gastric lavage, administration of saline laxatives, activated charcoal. Forced diuresis, hemodialysis, blood alkalinization, and symptomatic therapy aimed at supporting vital functions should be performed. In case of convulsive syndrome, intravenous administration of diazepam and fast-acting barbiturates is indicated; parenteral administration of cholinomimetics and anticholinesterase agents. For hyperthermia, wet sponging and antipyretic agents are recommended; for agitation – intravenous thiopental sodium or sodium oxybate; for mydriasis – topical application as eye drops of phosphacol, physostigmine, or pilocarpine. In case of glaucoma attack, immediately start instilling 2 drops of 1% pilocarpine solution into the conjunctival sac every hour and administer subcutaneously 1 mL of 0.05% proserine solution 3–4 times daily. Phenothiazines should not be used. In case of methemoglobinemia – intravenous administration of methylene blue. Treatment is symptomatic.

In case of first signs of overdose, seek immediate medical help.

Adverse Reactions

Belladonna extract.

Nervous system: headache, dizziness.

Urinary system: difficulty in urination, urinary retention.

Gastrointestinal system: dryness in the mouth, sensation of thirst, taste disturbances, dysphagia, decreased intestinal motility up to atony, reduced tone of bile ducts and gallbladder.

Eyes: mydriasis, photophobia, accommodation paralysis, blurred vision, increased intraocular pressure, transient visual disturbances.

Cardiovascular system: facial flushing, hot flushes, palpitations, arrhythmias (including extrasystoles), myocardial ischemia.

Respiratory system and mediastinal organs: decreased secretory activity and bronchial tone, leading to formation of viscous sputum difficult to expectorate.

Immune system: possible manifestations of hypersensitivity reactions, including anaphylactic reactions, anaphylactic shock.

Skin and subcutaneous tissue: skin rashes, pruritus, urticaria, exfoliative dermatitis, hyperemia.

Other: decreased sweating, dryness of the skin and mucous membranes, dysarthria.

Sodium metamizole.

Blood and lymphatic system: with prolonged use, agranulocytosis, leukopenia, thrombocytopenia, anemia, granulocytopenia may occur.

Urinary system: transient oliguria, anuria, proteinuria, and toxic nephropathy in various forms, including interstitial nephritis, usually occur in patients with impaired renal function and/or after administration of excessive doses. Red discoloration of urine may occur.

Immune system: possible manifestations of hypersensitivity reactions, including skin and mucous membrane rashes, conjunctivitis, pruritus, urticaria, angioneurotic edema (including Quincke's edema), bronchospastic syndrome, anaphylactic shock, Stevens-Johnson syndrome, Lyell's syndrome.

Nervous system: nervousness, insomnia, psychomotor agitation, seizures.

Cardiovascular system: tachycardia, decreased blood pressure.

Gastrointestinal tract: constipation, diarrhea.

Hepatobiliary system: drug-induced liver injury, including acute hepatitis, jaundice, elevated levels of liver enzymes (see section "Special instructions").

Methemoglobinemia may occur during use of the drug (skin, lips, and nail beds cyanosis, headache, dizziness, dyspnea, weakness, tachycardia) (the drug contains benzocaine).

If any adverse reactions occur, discontinue use of the drug and consult a physician immediately.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aіsf.dec.gov.ua.

Shelf life. 3 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 10 tablets in a blister, 1 blister per carton.

Dispensing category. Over-the-counter.

Manufacturer.

Public Joint-Stock Company "Scientific and Production Center "Borshchagovskiy Chemical and Pharmaceutical Plant".

Limited Liability Company "Agrofarm".

Manufacturer's name and address of place of business.

Ukraine, 03134, Kyiv, Miru St., 17.

Ukraine, 08200, Kyiv region, Irpin, Tsentralna St., 113-A.