Spazmalgon duo

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Spazmalgon DUO (SpasmalgonDUO)

Composition:

Active substances: metamizole sodium, pitoheptone hydrochloride, phenpiverine bromide;

1 tablet contains 500 mg of sodium metamizole, 5 mg of pitoheptone hydrochloride, 0.1 mg of phenpiverine bromide;

Excipients: lactose monohydrate, wheat starch, talc, magnesium stearate, gelatin, sodium bicarbonate.

Pharmaceutical form. Tablets.

Main physicochemical properties: round, flat tablets with bevelled edges, with a dividing line on one side, diameter 13 mm; color white or almost white.

Pharmacotherapeutic group.

Spasmolytics in combination with analgesics. Synthetic anticholinergics in combination with analgesics. Pitoheptone and analgesics. ATC code A03DA02.

Pharmacological properties.

Pharmacodynamics.

Spazmalgon DUO exhibits analgesic, spasmolytic (papaverine-like), anticholinergic (atropine-like), and some anti-inflammatory activity.

Metamizole exerts pronounced analgesic and antipyretic effects in combination 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 transmission of pain-related exteroceptive and interoceptive impulses in the CNS. It also affects the hypothalamus and the formation of endogenous pyrogens.

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

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

Pharmacokinetics.

Metamizole is rapidly and completely absorbed. Within 30 minutes after oral administration, serum levels reach 50% of the maximum plasma 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 genetically determined acetylation type. Data on absorption and distribution processes of pitofenone and fenpiverinium in available medical literature are very limited. It is known that absorption occurs in the upper gastrointestinal tract and is incomplete. These chemical compounds undergo significant ionization and have low lipophilicity, resulting in poor penetration through the blood-brain barrier. Their plasma concentration profile shows a biphasic pattern.

Pitofenone and fenpiverinium are metabolized in the liver, primarily via oxidation. Approximately 90% of the substance is excreted in urine as metabolites and about 10% in feces as unchanged compound. Available data indicate that their elimination half-life from blood plasma is approximately 10 hours. Some components are excreted in 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 accompanied by pain and dysuric disorders;
• Spasms of the stomach and intestines, biliary colic, biliary tract dyskinesia;
• Spastic dysmenorrhea.

Contraindications.

Hypersensitivity to metamizole, to pyrazolone or pyrazolidine derivatives, or to any other component of the medicinal product.

Gastrointestinal obstruction and megacolon.

Atony of the gallbladder or urinary bladder.

Severe impairment of kidney or liver function.

Blood disorders (agranulocytosis, leukopenia, anemia of any etiology, cytostatic or infectious neutropenia).

Glucose-6-phosphate dehydrogenase deficiency.

Porphyria.

Closed-angle glaucoma.

Suspicion of acute surgical pathology.

Bronchial asthma.

Collapse-like conditions.

Tachyarrhythmia.

Prostatic hyperplasia with tendency to urinary retention.

Pregnancy and breastfeeding.

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 the hematotoxic effect of myelotoxic medicinal products and chloramphenicol.

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

Temazepam and tricyclic antidepressants, oral contraceptives, allopurinol slow down the metabolism of metamizole and increase its toxicity.

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

Concomitant use of Spazmalgon DUO with other analgesics and nonsteroidal anti-inflammatory drugs increases the risk of developing allergic reactions.

Combining Spazmalgon DUO with other medicinal products requires special caution due to the presence of metamizole, which is an enzyme inducer. Metamizole can induce enzymes metabolizing medicinal products, including CYP2B6 and CYP3A4. Concomitant use of metamizole with bupropion, efavirenz, methadone, valproate, cyclosporine, tacrolimus, or sertraline may lead to decreased plasma concentrations of these drugs, potentially reducing their clinical efficacy. Therefore, caution is recommended when using metamizole concomitantly, and clinical response and/or drug levels should be monitored if necessary.

Special precautions for use.

The drug should be used with caution:

• in case of impaired kidney and/or liver function;
• in gastrointestinal disorders (achalasia, gastroesophageal reflux, pyloric stenosis);
• in patients predisposed to arterial hypotension and orthostatic reactions;
• in chronic bronchitis and bronchospasm (Spazmalgon DUO increases the viscosity of bronchial secretions);
• in the presence of hyperthyroidism or benign prostatic hyperplasia;
• in severe cardiac arrhythmias, ischemic heart disease (especially during acute myocardial infarction), chronic congestive heart failure;
• in patients with a history of hypersensitivity to nonsteroidal anti-inflammatory drugs and/or non-narcotic analgesics, or other allergic manifestations (e.g., allergic rhinitis).

During prolonged treatment with Spazmalgon DUO, peripheral blood status and liver function should be monitored regularly.

Headache may occur or worsen after prolonged analgesic therapy (>3 months) when analgesics are used daily or more frequently.

Headache caused by excessive analgesic use should not be treated by increasing the dose of the analgesic. In such cases, analgesic treatment should be discontinued after consultation with a physician.

The drug may affect the psychophysical state of patients when used concomitantly with alcohol or other central nervous system (CNS) depressants.

Concomitant use of other medicinal products containing metamizole is not recommended with Spazmalgon DUO.

Drug-induced liver injury. Cases of acute hepatitis, predominantly of hepatocellular type, have been reported in patients receiving metamizole, occurring from several days to several months after initiation of treatment. Signs and symptoms included elevated serum liver enzymes, with or without jaundice, often in the context of other drug hypersensitivity reactions (e.g., skin rash, blood dyscrasias, fever, and eosinophilia) or features 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 liver injury by metamizole is not fully understood, but available data suggest an immune-allergic nature. Patients should be advised to consult their physician if symptoms of liver injury occur. In such cases, metamizole should be discontinued and liver function should be evaluated. Re-administration of the drug is contraindicated in patients with a history of liver injury during previous treatment with metamizole when no other causes of liver injury have been identified.

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

Patients should be informed about the signs and symptoms of these reactions and monitored closely. If signs or symptoms suggestive of such reactions occur, metamizole should be discontinued immediately, and the drug must not be re-administered thereafter.

Wheat starch, gluten. This medicinal product contains a very small amount of gluten (considered gluten-free) and is unlikely to cause problems in patients with celiac disease. One tablet contains no more than 8.59 μg of gluten. This medicinal product should not be used in patients with wheat allergy (other than celiac disease).

Lactose. This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.

Metabolites of sodium metamizole may turn urine red, which is not of clinical significance.

Use during pregnancy or breastfeeding.

Spazmalgon DUO is contraindicated during pregnancy and breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

Caution is advised when driving or operating machinery during treatment with Spazmalgon DUO, as the cholinolytic effect of prolonged use may cause dizziness and accommodation disturbances.

Method of Administration and Dosage

Spazmalgon DUO 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 Spazmalgon DUO use should not exceed 3 days.

For elderly patients, debilitated patients, and patients with reduced creatinine clearance, the dose should be reduced, as elimination of metamizole metabolites may be prolonged.

Hepatic and renal impairment. Since the elimination rate of metamizole in patients with hepatic or renal impairment is reduced, repeated high doses of metamizole should be avoided. Dose reduction is not required for short-term use. Currently, there is insufficient experience regarding long-term use of metamizole in patients with severe hepatic and renal impairment.

Children

Spazmalgon DUO is not indicated for children under 15 years of age.

Overdose

Symptoms. In case of overdose, symptoms of metamizole intoxication in combination with anticholinergic effects predominate; liver and kidney dysfunction, respiratory paralysis. Toxic-allergic syndrome is most commonly observed, along with symptoms of hematopoietic system disorders, gastrointestinal disturbances, and, in severe cases, symptoms of brain involvement.

Treatment. In case of suspected overdose, the drug must be discontinued immediately, and measures should be taken for its rapid elimination from the body (induce vomiting, perform gastric lavage, increase urine output). Symptomatic treatment is administered. There is no specific antidote.

Adverse reactions.

Adverse reactions during the use of Spazmalgon DUO are usually temporary and disappear after discontinuation of treatment.

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

Immune system: urticaria, skin rashes, itching, conjunctivitis; rarely – bronchospasm, angioneurotic edema, anaphylactic shock, toxic epidermal necrolysis and Stevens-Johnson syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS).

Gastrointestinal tract: discomfort, dry mouth, intestinal obstruction, exacerbation of gastritis and peptic ulcer of the stomach and duodenum.

Hepatobiliary system: drug-induced liver injury, including acute hepatitis, jaundice, and increased serum liver enzymes (see section "Special precautions").

Cardiovascular system: palpitations, decreased blood pressure, tachycardia, cardiac arrhythmia.

Nervous system: dizziness, visual disturbances.

Blood and lymphatic system: granulocytopenia, anemia, agranulocytosis, thrombocytopenia, leukopenia.

Urinary system: oliguria, anuria, urinary retention, proteinuria, red discoloration of urine, development of acute renal failure and interstitial nephritis. With prolonged use of high doses, decreased kidney function is possible (especially in patients with a history of kidney disease); in some cases – papillary necrosis.

Other: reduced sweating.

Shelf life. 2 years.

Storage conditions.

Store in a dry, protected from light place, at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

Tablets № 10×1, № 10×2, № 10×5, № 20×1 in blisters, in a pack.

Availability. Over-the-counter.

Manufacturer.

Balkanpharma-Dupnitsa AD.

Manufacturer's address and place of business.

3 Samokovsko Shose Str., Dupnitsa, 2600, Bulgaria.