Spazmolix

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

Composition:

Active substances: sodium metamizole (analgin), pitofenone hydrochloride, fenpiverinium bromide;

One tablet contains: sodium metamizole (analgin) - 500 mg, pitofenone hydrochloride - 5.0 mg, fenpiverinium bromide - 0.1 mg;

Excipients: potato starch, calcium stearate.

Pharmaceutical form. Tablets.

Main physico-chemical properties: tablets of white or white with a yellowish tint, with a flat surface, a score line and bevelled edges.

Pharmacotherapeutic group. Spasmolytics in combination with analgesics. Synthetic anticholinergics in combination with analgesics. Pitofenone and analgesics.

ATC code A03DA02.

Pharmacological properties.

Pharmacodynamics.

Spazmolix combines analgesic, spasmolytic (papaverine-like), cholinolytic (atropine-like), and some anti-inflammatory activities.

Metamizole exerts a pronounced analgesic and antipyretic effect in combination with less pronounced anti-inflammatory and spasmolytic activities. Its effects result from inhibition of prostaglandin and endogenous algogen synthesis, elevation of excitation threshold in the thalamus, and modulation of pain-related exteroceptive and interoceptive impulse transmission in the central nervous system (CNS). It also affects the hypothalamus and the formation of endogenous pyrogens.

Phenpyrronium exerts moderate ganglion-blocking and parasympatholytic effects, reducing the tone and motility of the smooth musculature of the stomach, intestines, biliary and urinary tracts.

Pitofenone exerts a papaverine-like effect on vascular and non-vascular smooth muscle, with a pronounced spasmolytic character.

Pharmacokinetics.

Metamizole is rapidly and completely absorbed. Within 30 minutes after oral administration, serum levels reach 5% of the maximum serum concentration. It is partially bound to plasma proteins. The drug undergoes extensive biotransformation in the body, with its main metabolites being pharmacologically active. It is eliminated in urine in the form of metabolites. Only 3% of the excreted amount is unchanged metamizole. The extent of biotransformation is also influenced by the genetically determined acetylation type. Some components are excreted in breast milk.

Clinical characteristics.

Indications.

Symptomatic treatment of mild to moderate pain syndrome associated with spasms of smooth muscles of internal organs:

• renal colic and inflammatory diseases of the urinary tract occurring with pain and dysuric disorders;
• spasms of the stomach and intestines, hepatic colic, biliary tract dyskinesia;
• spasmodic dysmenorrhea.

Contraindications.

Hypersensitivity to metamizole, pyrazolone derivatives, other nonsteroidal anti-inflammatory drugs (NSAIDs), or any component of the medicinal product. Gastrointestinal obstruction and megacolon; bladder or gallbladder atony; severe impairment of kidney or liver function; changes in peripheral blood composition (agranulocytosis, leukopenia, aplastic anemia); blood disorders (anemia of any etiology, cytostatic or infectious neutropenia); history of agranulocytosis caused by metamizole, other pyrazolones or pyrazolidines; bone marrow dysfunction or hematopoietic system disorders; glucose-6-phosphate dehydrogenase deficiency; hepatic porphyria; closed-angle glaucoma; suspected acute surgical pathology; bronchial asthma; hypotensive conditions (including collapse-like states) and hemodynamic instability; tachyarrhythmia; prostatic hyperplasia with tendency to urinary retention.

Interaction with other medicinal products and other forms of interaction.

Metamizole increases plasma concentrations of chloroquine, reduces plasma concentrations and effects of coumarin anticoagulants and cyclosporine.

Enhances hematotoxic effects of myelotoxic drugs and chloramphenicol.

Risk of hypersensitivity reactions and adverse effects increases when used concomitantly with NSAIDs.

Metamizole enhances the sedative effect of ethanol; simultaneous use with chlorpromazine or other phenothiazine derivatives may lead to pronounced hypothermia. Should not be used with radiographic contrast agents, colloidal plasma substitutes, or penicillin. Metamizole increases the activity of oral hypoglycemic agents, sulfonamide drugs, indirect anticoagulants, glucocorticosteroids, phenytoin, ibuprofen, and indomethacin by displacing them from protein binding sites. Sarcolysin, mercazole (thiamazole), and drugs that suppress bone marrow activity, including gold compounds, increase the likelihood of hematotoxicity, including development of leukopenia.

Neuroleptics, sedatives, and tranquilizers enhance the analgesic effect of metamizole.

Temperidone and tricyclic antidepressants, oral contraceptives, and allopurinol impair metamizole metabolism and increase its toxicity.

Barbiturates, phenylbutazone, glutethimide, and other hepatic microsomal enzyme inducers may reduce the effect of metamizole.

Concomitant use of Spazmolix with other analgesics and nonsteroidal anti-inflammatory drugs increases the risk of developing toxic effects.

Metamizole reduces plasma concentrations of cyclosporine A, and its concomitant use may be risky in cases of existing tissue transplantation.

Combination of Spazmolix with other medicinal products requires special caution due to the presence of metamizole, which is an enzyme inducer.

Spazmolix can be combined with M-cholinolytics, quinidine, and codeine, as it exhibits synergy with these agents.

It is known that pyrazolone derivatives may interact with captopril, lithium, methotrexate, and triamterene, as well as alter the effectiveness of antihypertensive agents and diuretics. The extent to which these properties are expressed in metamizole is unknown.

H2-receptor antagonists of histamine and caffeine enhance the effect of sodium metamizole when used concomitantly.

Special precautions.

Before starting treatment with the drug, consult a physician. Do not use the medicinal product for longer than the recommended duration without consulting a physician.

Do not exceed the recommended doses of the drug.

Do not use the drug to relieve acute abdominal pain (before determining the cause).

The drug should be used with caution in the following cases:

• in renal and/or hepatic impairment;
• in gastric disorders (achalasia, gastroesophageal reflux, pyloric stenosis);
• in inflammatory bowel diseases (including ulcerative colitis and Crohn's disease);
• in predisposition to arterial hypotension and orthostatic reactions;
• in chronic bronchitis and bronchospasm (Spazmolix increases the viscosity of bronchial secretions);
• in hyperthyroidism;
• in cardiac rhythm disorders, ischemic heart disease (especially acute myocardial infarction), chronic congestive heart failure;
• in patients with a history of hypersensitivity to nonsteroidal anti-inflammatory drugs, non-narcotic analgesics, or other allergic manifestations (allergic rhinitis);
• when used concomitantly with cytostatic drugs (only under medical supervision), and in elderly patients (which may lead to an increased frequency of adverse reactions, particularly gastrointestinal).

Severe skin reactions

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced eosinophilia with systemic symptoms (DRESS syndrome), which may be life-threatening or fatal, have been reported during treatment with metamizole.

Patients should be informed about the signs and symptoms of skin reactions and closely monitored.

If signs or symptoms suggestive of these reactions occur, treatment with metamizole should be discontinued and must never be restarted (see section "Contraindications").

Risk of drug-induced liver injury

Cases of acute hepatitis, predominantly hepatocellular in nature, have been observed in patients treated with sodium metamizole. Symptoms appeared from several days to several months after initiation of treatment. Manifestations included elevated serum liver enzymes, with or without jaundice, often in the context of hypersensitivity reactions to other drugs (e.g., skin rash, blood dyscrasias, fever, and eosinophilia) or features of autoimmune hepatitis. Most patients recovered after discontinuation of sodium metamizole; however, in isolated cases, progression to liver failure requiring liver transplantation has been reported.

The mechanism of sodium metamizole-induced liver injury is not fully understood, but available data suggest an immune-allergic mechanism.

Patients should be instructed to promptly inform their physician if symptoms suggestive of liver injury occur. In suspected cases of liver injury, patients should discontinue sodium metamizole, and liver function tests should be performed.

Cases of liver injury during treatment with sodium metamizole are very rare, but the exact frequency of this adverse reaction cannot be determined. Hepatic injury has recurred in some patients upon re-exposure to sodium metamizole. Therefore, if a patient previously experienced liver injury during treatment with sodium metamizole and no other cause of liver injury has been identified, drugs containing sodium metamizole should not be used again.

If symptoms of impaired liver function occur, including gastrointestinal disturbances, jaundice, or elevated liver enzymes, the drug must be discontinued.

When Spazmolix is used beyond the recommended 3-day period, peripheral blood status (leukocyte formula) and liver function should be monitored.

Headache may appear or existing headache may worsen after prolonged analgesic treatment (> 3 months) with daily or more frequent use of analgesics.

Analgesic-overuse headache should not be treated by increasing the analgesic dose. In such cases, analgesic treatment should be discontinued after consultation with a physician.

Spazmolix contains the active substance metamizole. Metamizole may cause agranulocytosis and thrombocytopenia. The development of agranulocytosis is not dose-dependent and cannot be predicted; it may occur after the first dose or after repeated administration. Typical symptoms of agranulocytosis include fever, sore throat, painful swallowing, and inflammation of the mucous membranes of the mouth, nose, pharynx, anorectal, and genital areas. If a sudden deterioration in general condition occurs with signs of agranulocytosis, treatment with metamizole should be stopped immediately and a complete blood count should be performed.

Because metamizole has anti-inflammatory and analgesic properties, it may mask signs of infection, symptoms of non-infectious diseases, and complications associated with pain, which may complicate their diagnosis.

The drug may affect the psychophysical state of patients when used concomitantly with alcohol and CNS depressants.

It is not recommended to use other medicinal products containing metamizole simultaneously with Spazmolix.

Metabolites of sodium metamizole may change the color of urine to red, which has no clinical significance.

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

Use during pregnancy or breastfeeding

Do not use during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery

Use with caution in drivers and individuals operating complex machinery. With prolonged use of the drug, its cholinolytic effect may lead to dizziness or accommodation disorders.

Method of Administration and Dosage

Spazmolix tablets are taken orally after meals with water. The recommended daily dose for adults and children aged 15 years and older is 1–2 tablets per day; the maximum daily dose is 2 tablets.

The duration of treatment with Spazmolix should not exceed 3 days.

Patients aged 65 years and older

Dosage adjustment is generally not required. However, for patients with age-related impairment of liver or kidney function, dosage reduction may be necessary due to a possible prolonged elimination half-life of metamizole metabolites.

Patients with impaired renal function

Metamizole is excreted in urine as metabolites. For patients with mild or moderate renal impairment, it is recommended to use ½ of the adult dose.

Patients with impaired hepatic function

In such patients, the elimination half-life of active metabolites of metamizole may be prolonged. High doses should be avoided in patients with impaired liver function. Dose reduction is not usually necessary for short-term use. There is insufficient experience regarding prolonged use in patients with impaired renal or hepatic function.

Children.

Spazmolix is not prescribed for children under 15 years of age.

Overdose.

Symptoms of overdose may include nausea, vomiting, decreased arterial pressure, confusion, impaired liver and kidney function, toxic-allergic syndrome, seizures, hypothermia with bulbar paresis, respiratory disturbances, paralysis of the respiratory tract, collapse, or coma. Rarely, agranulocytosis, aplastic and hemorrhagic anemias, and hemorrhagic diathesis may occur.

Treatment: In case of suspected overdose, the drug should be discontinued immediately, and measures should be taken to rapidly eliminate it from the body: gastric lavage, administration of activated charcoal, forced diuresis, artificial ventilation of the lungs, anti-shock and symptomatic therapy. There is no specific antidote.

Side effects.

The side effects listed below are mainly caused by metamizole, which is a component of the medicinal product.

Immune system disorders: fixed drug eruption, maculopapular rash, anaphylactic or anaphylactoid reactions, asthma attack (in patients with analgesic-induced asthma), Stevens-Johnson syndrome or Lyell's syndrome, circulatory shock.

Milder reactions manifest as typical skin and mucous membrane reactions (e.g., itching, burning, erythema, urticaria, swelling), dyspnea; gastrointestinal reactions may rarely occur. Such milder reactions may progress into more severe forms with generalized urticaria, severe angioneurotic edema (including laryngeal edema), severe bronchospasm, cardiac arrhythmia, decreased blood pressure (sometimes preceded by increased blood pressure).

Severe skin reactions have been reported with metamizole use, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug-induced eosinophilia with systemic symptoms (DRESS syndrome) (see section "Special precautions").

Skin and subcutaneous tissue disorders: drug-induced eosinophilia with systemic symptoms (DRESS syndrome) (frequency unknown).

Gastrointestinal disorders: dry mouth, nausea, vomiting, abdominal pain and discomfort, constipation, exacerbation of gastritis and peptic ulcer disease; in rare cases, ulceration and gastrointestinal bleeding, hepatitis.

Hepatobiliary disorders: increased liver transaminase activity, impaired liver function, hepatitis, jaundice, drug-induced liver injury, including acute hepatitis (see section "Special precautions").

Cardiac disorders: palpitations, tachycardia, cyanosis.

Vascular disorders: arterial hypotension, cardiac arrhythmia.

Blood and lymphatic system disorders: leukopenia, agranulocytosis, thrombocytopenia, anemia including hemolytic and aplastic anemia, granulocytopenia.

The risk of developing agranulocytosis cannot be predicted. Agranulocytosis may occur even in patients who previously used metamizole without experiencing adverse reactions.

Nervous system disorders: dizziness.

Eye disorders: visual disturbances, accommodation disorders.

Renal and urinary disorders: proteinuria, oliguria, anuria, polyuria, interstitial nephritis, red discoloration of urine, urinary retention, acute renal failure.

Other: decreased sweating.

If any adverse reactions occur, the use of the medicinal product should be discontinued immediately and medical advice should be sought.

Shelf life.

2 years.

Do not use 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 and sight of children.

Packaging.

10 tablets in blisters.

10 tablets per blister; 1 or 2 blisters per cardboard pack.

Supply category.

Over-the-counter.

Manufacturer.

PJSC "CHEMICAL PHARMACEUTICAL PLANT "CHERVONA ZIRKA".

Manufacturer's address and place of business.

1, Gordiyenkivska Street, Kharkiv, Kharkiv Oblast, 61010, Ukraine.