Spazmil

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

Composition:

Active substances: metamizole sodium monohydrate, pitofenone hydrochloride, fenpiverinium bromide.

One tablet contains: metamizole sodium monohydrate 500 mg, pitofenone hydrochloride 5.25 mg, fenpiverinium bromide 0.1 mg;

Excipients: microcrystalline cellulose, wheat starch, lactose monohydrate, povidone K-25, talc, magnesium stearate, sodium hydrocarbonate, colloidal anhydrous silicon dioxide.

Pharmaceutical form. Tablets.

Main physicochemical properties: round, flat tablets with bevel and score line, 13 mm in diameter, white to almost white in color, odorless.

Pharmacotherapeutic group.

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

ATC code A03DA02.

Pharmacological properties.

Pharmacodynamics.

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

Metamizole exerts pronounced analgesic and antipyretic effects, along with less pronounced anti-inflammatory and spasmolytic activity. 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. Metamizole also affects the hypothalamus and the formation of endogenous pyrogens.

Fenpiverinium exerts moderate ganglion-blocking and anticholinergic effects, reducing tone and motility of smooth musculature of the stomach, intestine, biliary, and urinary tracts.

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

Pharmacokinetics.

Metamizole is characterized by rapid and complete absorption. Within 30 minutes after oral administration, serum levels reach 5% of the maximum serum concentration. It is partially bound to plasma proteins. In the body, it undergoes extensive biotransformation, with its main metabolites being pharmacologically active. Elimination occurs via urine in the form of metabolites. Only 3% of the excreted amount is unchanged metamizole. The extent of biotransformation is also influenced by genetically determined acetylation type. Some components pass into breast milk.

Clinical characteristics.

Indications.

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

• Renal colic and inflammatory diseases of the urinary tract occurring with pain and dysuric disorders;
• Gastric and intestinal spasms, biliary colic, biliary tract dyskinesia;
• Primary and secondary dysmenorrhea.

Contraindications.

• Hypersensitivity to metamizole, pyrazolone derivatives, or other nonsteroidal anti-inflammatory drugs (NSAIDs), or to any component of the drug;
• History of agranulocytosis induced by metamizole, other pyrazolones, or pyrazolidines;
• Bone marrow dysfunction (e.g., following cytostatic therapy) or hematopoietic system disorders (leukopenia, aplastic anemia);
• Blood disorders (anemia of various etiologies, cytostatic or infectious neutropenia);
• Severe impairment of liver function;
• Severe impairment of kidney function;
• Atony of the gallbladder or urinary bladder;
• Glucose-6-phosphate dehydrogenase deficiency;
• Tachyarrhythmias;
• Acute hepatic porphyria;
• Closed-angle glaucoma;
• Benign prostatic hyperplasia with tendency to urinary retention;
• Gastrointestinal obstruction and megacolon;
• Hypotensive states (including collapse-like conditions) and hemodynamic instability;
• Suspected acute surgical pathology;
• Bronchial asthma.

Interaction with other medicinal products and other forms of interactions.

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

Concomitant use with other pyrazolone analgesics is not recommended. Combined use with chloramphenicol, cytostatics, and other myelotoxic agents enhances myelotoxic effects. Metamizole increases plasma concentrations of chloroquine, reduces plasma concentrations and effects of coumarin anticoagulants and cyclosporine. The risk of hypersensitivity reactions and adverse effects is increased when used concomitantly with NSAIDs.

Metamizole enhances the sedative effect of ethanol. Concurrent use with chlorpromazine or other phenothiazine derivatives may lead to the development of pronounced hypothermia. It is not recommended to use with radiopaque substances, colloidal plasma substitutes, or penicillin. Metamizole increases the activity of oral hypoglycemic agents, sulfonamides, indirect anticoagulants, glucocorticoids, phenytoin, ibuprofen, and indomethacin by displacing them from protein binding sites. Sarcollisin, mercaptopurine (thiamazole), agents that suppress bone marrow activity, including gold compounds, increase the likelihood of hematotoxicity, including development of leukopenia.

Allopurinol, tranquilizers, tempidone, tricyclic antidepressants, neuroleptics, and oral contraceptives increase the toxicity of Spazmal due to impaired hepatic metabolism. Neuroleptics, sedatives, and tranquilizers enhance the analgesic effect of metamizole. Barbiturates, phenylbutazone, glutethimide, and other inducers of hepatic microsomal enzymes may reduce the effect of metamizole. Metamizole reduces plasma concentrations of cyclosporine A, and its concomitant use may be risky in tissue transplantation. Spazmal can be combined with M-cholinolytics, quinidine, and codeine, as it exhibits synergism with these agents.

For the class of pyrazolone derivatives, it is known that they 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.

Since metamizole may reduce the effect of certain drugs, Spazmal should be used with caution in combination with the following medicinal products:

• Bupropion – used for treatment of depression or as an aid to smoking cessation;
• Efavirenz – used for treatment of HIV/AIDS;
• Methadone – used for treatment of addiction to illicit substances (so-called opioids);
• Valproate – used for treatment of epilepsy or bipolar disorder;
• Tacrolimus – used to prevent organ rejection in transplant patients;
• Sertraline – used for treatment of depression.

Special precautions for use.

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

Do not exceed the recommended doses of the medicinal product.

Do not use the medicinal product to relieve acute abdominal pain (until the cause is determined).

The medicinal product should be used with caution in patients with moderate renal and/or hepatic impairment, gastric disorders (achalasia, gastroesophageal reflux, pyloric stenosis), inflammatory bowel diseases (including ulcerative colitis and Crohn's disease), predisposition to arterial hypotension and orthostatic reactions, chronic bronchitis and bronchospasm, hyperthyroidism, cardiac rhythm disorders (in tachyarrhythmia – see section "Contraindications"), ischemic heart disease (especially during acute myocardial infarction), chronic congestive heart failure, hypersensitivity to non-narcotic analgesics or other manifestations of allergy (allergic rhinitis), concomitant use of cytostatic drugs (only under physician supervision), and in elderly patients (may lead to increased frequency of adverse reactions, especially those affecting the gastrointestinal tract).

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 indicating these reactions occur, treatment with metamizole should be discontinued and must never be restarted (see section "Contraindications").

When using Spazmил for longer than the recommended 3-day period, it is necessary to check and monitor peripheral blood status (leukocyte formula) and liver function.

Spazmil contains the active substance metamizole. Metamizole may cause thrombocytopenia.

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

Concomitant use of Spazmil with other medicinal products containing sodium metamizole is not recommended.

Hepatitis has been observed in patients who have used metamizole, with symptoms developing from several days to several months after initiation of treatment.

If a patient develops symptoms that may indicate liver injury, such as nausea or vomiting, elevated body temperature, fatigue, loss of appetite, dark urine, pale stools, jaundice of the skin or sclera, pruritus, rash, or upper abdominal pain, they must discontinue use of the medicinal product Spazmil and consult a physician. The physician should assess the patient's liver function.

Spazmil should not be used if the patient has previously experienced liver injury during treatment with metamizole.

The medicinal product may affect the psychophysical state of patients when used concomitantly with alcohol and central nervous system depressants.

Wheat starch contained in the tablet may contain only trace amounts of gluten and is considered safe for individuals with celiac disease (gluten-sensitive enteropathy). Patients with wheat allergy (not celiac disease) should not take this medicinal product.

The medicinal product contains lactose. This medicinal product must not be used by patients with rare hereditary forms of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

This medicinal product contains 34 mg of sodium per dose. This should be taken into account if the patient is on a sodium-controlled diet.

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

If disease symptoms do not begin to subside, or if the patient's condition worsens, or if adverse effects occur, treatment with the medicinal product should be discontinued and a physician should be consulted regarding further management.

Use during pregnancy or breastfeeding.

Use during pregnancy or breastfeeding is contraindicated.

Ability to affect reaction speed when driving or operating machinery.

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

Method of Administration and Dosage

The drug should be taken orally, swallowed with a small amount of liquid after meals.

Adults and children aged 15 years and older

For adults and children aged 15 years and older – 1–2 tablets per day. Maximum daily dose – 2 tablets.

Patients aged 65 years and older

Dose adjustment is usually not required. However, dosage reduction is necessary for patients with age-related impaired liver or kidney function, as this may lead to prolonged elimination half-life of metamizole metabolites.

Patients with impaired kidney function

Metamizole is excreted in urine in the form of metabolites. For patients with mild or moderate kidney dysfunction, it is recommended to use ½ of the adult dose.

Patients with impaired liver 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 required for short-term use. There is insufficient experience regarding prolonged use in patients with impaired kidney or liver function.

Duration of Spazmil use – no more than 3 days.

Children

The use of the drug is contraindicated in children under 15 years of age.

Overdose

In case of accidental ingestion of a large number of tablets, symptoms may include nausea, vomiting, decreased arterial pressure, confusion, impaired liver and kidney function, toxic-allergic syndrome, seizures, hypothermia with bulbar paresis, respiratory disturbances, airway paralysis, collapse, or coma. Rarely, agranulocytosis, aplastic and hemorrhagic anemias, and hemorrhagic diathesis may occur.

Treatment: gastric lavage, activated charcoal administration, 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), Lyell's syndrome (toxic epidermal necrolysis), circulatory shock.

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

Skin and subcutaneous tissue disorders: severe skin reactions have been reported, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and (with unknown frequency) drug-induced eosinophilia with systemic symptoms (DRESS) associated with metamizole use (see section "Special precautions for use").

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

Hepatobiliary disorders: drug-induced liver injury, including acute hepatitis, jaundice, elevated liver enzymes.

Cardiac disorders: palpitations, tachycardia, cyanosis.

Vascular disorders: arterial hypotension.

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

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: 3 years.

Storage conditions:

Store out of reach of children. Store in the original packaging (in a dry, light-protected place) at a temperature not exceeding 25 °C.

Packaging:

10 tablets in a blister pack made of PVC film/aluminum foil. 2 blisters in a cardboard box.

Supply category: Over-the-counter (without prescription).

Manufacturer:

Sofarma AD

Manufacturer's address and location of business activity:

16 Iliensko Shose Street, Sofia, 1220, Bulgaria.