Analgin
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT A N A L G I N (ANALGIN)
Composition:
Active substance: metamizole sodium;
1 ml of solution contains 500 mg of sodium metamizole;
Excipients: anhydrous sodium sulfite (E 221), sodium formaldehyde sulfoxylate dihydrate, diluted hydrochloric acid, water for injections.
Pharmaceutical form. Solution for injection.
Main physicochemical properties: clear, colorless or slightly yellowish liquid.
Pharmacotherapeutic group. Analgesics and antipyretics. Sodium metamizole.
ATC code N02B B02.
Pharmacological properties.
Pharmacodynamics.
An analgesic, antipyretic, and spasmolytic agent (acts on the smooth musculature of the urinary and biliary tracts) belonging to the pyrazolone derivatives group. Its anti-inflammatory effect is weak.
The mechanism of action is due to cyclooxygenase inhibition, resulting in reduced synthesis of prostaglandins, which mediate pain, temperature elevation, and increased tissue permeability at the site of inflammation. The drug also impairs transmission of nociceptive and proprioceptive impulses and increases the excitation threshold of thalamic pain sensitivity centers, enhancing heat dissipation.
Pharmacokinetics.
After administration, metamizole is hydrolyzed to its active metabolite (following intravenous administration, unchanged metamizole is detected in plasma only in negligible amounts). Plasma protein binding of the active metabolite is 50–60%. Metabolized in the liver and excreted by the kidneys. It crosses the placental barrier and is excreted into breast milk.
Clinical characteristics.
Indications.
Mild to moderate pain of various origins and localizations (headache, toothache, burns, postoperative pain, dysmenorrhea, arthralgia, neuralgia, radiculitis, myositis); hyperthermic syndrome and febrile conditions (influenza, acute respiratory and other infections); renal and hepatic colic (in combination with spasmolytic agents).
Contraindications.
Hypersensitivity to metamizole sodium, other pyrazolone derivatives, or any component of the drug.
History of metamizole-induced agranulocytosis or agranulocytosis caused by other pyrazolones or pyrazolidines.
Bronchial asthma attacks induced by acetylsalicylic acid.
Bone marrow dysfunction or hematopoietic system disorders. Blood dyscrasias (agranulocytosis, cytostatic or infectious neutropenia). Hepatic and/or renal insufficiency.
Hereditary hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency.
Abdominal pain of unknown origin.
Anemia, leukopenia.
Kidney diseases: pyelonephritis, glomerulonephritis, including in medical history.
Intravenous administration is contraindicated in patients with systolic arterial pressure below 100 mm Hg.
Polytrauma.
Shock.
Porphyria.
Third trimester of pregnancy.
Interaction with other medicinal products and other types of interactions.
Due to a high risk of pharmaceutical incompatibility, the drug must not be mixed with other medicinal products in the same syringe.
Ethanol – enhances the effect of ethanol.
Chlorpromazine or other phenothiazine derivatives – concomitant use may lead to pronounced hypothermia.
X-ray contrast agents, colloidal plasma substitutes, and penicillin should not be used during treatment with analgin.
Oral hypoglycemic agents, indirect anticoagulants, glucocorticosteroids, phenytoin, ibuprofen, and indometacin – metamizole sodium increases the activity of these drugs by displacing them from protein binding.
Phenylbutazone, barbiturates, and other hepatic enzyme inducers reduce the efficacy of metamizole sodium when used concomitantly.
Non-opioid analgesics, tricyclic antidepressants, hormonal contraceptives, and allopurinol – concomitant use with metamizole sodium may increase its toxicity.
Other nonsteroidal anti-inflammatory drugs (NSAIDs) – enhance their analgesic and antipyretic effects, but also increase the risk of additive adverse effects.
Sedatives and tranquilizers (diazepam, trioxazine, valocordin) enhance the analgesic effect of metamizole sodium.
Sarcolysin, mercazole (thiamazole), and drugs that suppress bone marrow activity, including gold compounds – increase the risk of hematotoxicity, including leukopenia.
Codeine, histamine H2-blockers, and propranolol enhance the effect of metamizole sodium.
Caution is required when using the drug concomitantly with sulfonylurea hypoglycemic agents (enhanced hypoglycemic effect) and diuretics (furosemide).
Myelotoxic medicinal products lead to increased hematotoxicity.
Metotrexate – high doses of metamizole may increase metotrexate plasma concentration and enhance its toxic effects (on the gastrointestinal tract and hematopoietic system).
Pharmacokinetic induction of metabolizing enzymes – metamizole may induce metabolic enzymes, including CYP2B6 and CYP3A4.
Concomitant use of metamizole with bupropion, efavirenz, methadone, valproate, cyclosporine, tacrolimus, or sertraline may reduce plasma concentrations of these drugs, potentially decreasing their clinical efficacy. Therefore, concomitant use of metamizole is recommended with caution; clinical response and/or drug levels should be monitored if co-administration is necessary.
Special precautions for use.
| Agranulocytosis Treatment with metamizole may cause agranulocytosis, including fatal cases (see section "Side Effects"). This condition may occur even if previous use of metamizole was without adverse consequences. Metamizole-induced agranulocytosis is an idiosyncratic adverse reaction unrelated to dose and may occur at any time during treatment, as well as shortly after its discontinuation. Patients should be informed of the necessity to discontinue treatment and immediately seek medical assistance if any symptoms indicating 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 area). If metamizole is used during fever, some symptoms of developing agranulocytosis may remain unnoticed. Similarly, these symptoms may go undetected in patients receiving antibiotic therapy. In the event of signs and symptoms suggestive of agranulocytosis, treatment should be immediately discontinued and a complete blood count should be performed. If the diagnosis is confirmed, treatment must not be resumed (see section "Contraindications"). |
When administered parenterally, medical supervision is required (due to a high frequency of allergic reactions, including those with fatal outcomes), as well as availability of conditions for emergency anti-shock therapy.
Patients with atopic bronchial asthma and pollinosis have an increased risk of developing hypersensitivity reactions.
The drug must not be used to relieve acute abdominal pain of unknown origin (until the cause is established).
The medicinal product should be used with caution in the following patients:
- Elderly patients – may lead to an increased incidence of adverse reactions, particularly those affecting the gastrointestinal system;
- Patients with inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease.
Careful monitoring of hemodynamics is required when prescribing to patients with acute cardiovascular disorders. Use with caution in patients with blood pressure below 100 mm Hg, myocardial infarction, history of liver or kidney diseases (pyelonephritis, glomerulonephritis), during treatment with cytostatics, chronic alcoholism, a history of allergic disorders, or blood disorders.
Regular long-term use of the medicinal product is not recommended due to the myelotoxic potential of metamizole sodium; peripheral blood picture (leukocyte formula) should be monitored.
Serious skin adverse reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported with metamizole use, which may be life-threatening or fatal. Patients should be informed about the signs and symptoms and closely monitored for skin reactions.
If a patient develops signs or symptoms suggestive of such reactions, metamizole should be discontinued immediately and reinitiation of treatment is contraindicated.
Subcutaneous administration of the drug is not recommended due to the possibility of tissue irritation.
During treatment, red discoloration of urine may occur (due to excretion of a metabolite), which has no clinical significance.
Special patient groups
Elderly, debilitated patients, and patients with reduced creatinine clearance
The dose of the drug should be reduced in these patient groups, as elimination of metamizole metabolites may be prolonged.
Patients with hepatic or renal impairment
Since the rate of elimination of the drug is reduced in patients with impaired renal or hepatic function, repeated high doses should be avoided. Dose reduction is not necessary for short-term use. Currently, there is no experience with long-term use of metamizole in patients with severe hepatic or renal impairment.
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 include elevated serum liver enzymes, with or without jaundice, often accompanied by 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 metamizole-induced liver injury is not fully understood, but evidence suggests an immune-allergic mechanism.
Patients should be advised to consult their physician if symptoms suggestive of liver injury occur. In such patients, metamizole should be discontinued and liver function should be evaluated.
Metamizole should not be re-prescribed to patients with a history of liver injury during previous metamizole treatment, unless no other cause of liver injury has been identified.
This medicinal product contains 1.469 mmol (or 33.77 mg)/dose (1 mL) of sodium. Caution is advised when administering to patients on a sodium-controlled diet.
Use during pregnancy or breastfeeding
Pregnancy
Data on the use of metamizole in pregnant women are limited. According to published data, no evidence of teratogenic or embryotoxic effects was observed in pregnant women who received metamizole during the first trimester (n=568). Single doses of metamizole during the first and second trimesters may be acceptable in individual cases if no alternative treatment options are available. However, overall, the use of metamizole during the first and second trimesters of pregnancy is not recommended. Use of metamizole during the third trimester is associated with fetotoxic effects (impaired renal function and constriction of the arterial duct); therefore, the use of the drug is contraindicated during the third trimester of pregnancy (see section "Contraindications"). In case of inadvertent use of metamizole during the third trimester, amniotic fluid volume and the arterial duct should be monitored by ultrasound and echocardiography.
Metamizole crosses the placental barrier.
In animal studies, metamizole caused reproductive toxicity but did not show teratogenic effects.
Breastfeeding
Metabolites of metamizole are excreted in breast milk in significant amounts, and the risk of effects on the breastfed infant cannot be excluded. Therefore, the use of metamizole, especially repeated administration, should be avoided during breastfeeding. After a single dose of metamizole, breastfeeding should be discontinued for 48 hours following administration.
Ability to affect the speed of reactions when driving or operating machinery
During treatment, patients should not drive or engage in other potentially hazardous activities requiring high concentration and rapid psychomotor responses.
Method of Administration and Dosage
Administer intramuscularly or intravenously as a slow bolus injection. The route of administration and dosage depend on the severity of the disease and should be determined individually, taking into account sensitivity to the drug. It is important to use the lowest effective dose.
The solution to be administered should be at body temperature. To prevent a sudden drop in arterial blood pressure, intravenous injection must be performed very slowly. The patient should be in a supine position, and monitoring of arterial pressure, heart rate, and respiration is required. The procedure requires availability of conditions for shock therapy if needed. A long needle must be used for intravenous administration.
For children and adolescents up to 14 years of age, a single dose of 8–16 mg of metamizole per kilogram of body weight may be used. In cases of fever, a dose of 10 mg of metamizole per kilogram of body weight is generally sufficient for children. For adults and adolescents aged 15 years and older (> 53 kg), a single dose of up to 1000 mg may be administered.
The daily dose may be divided into 4 doses, administered at 6–8 hour intervals.
The effect of the drug is expected within 30 minutes after parenteral administration.
The table below provides recommended single doses and maximum daily doses based on body weight or age:
| Body weight |
Single dose |
Maximum daily dose |
|||
| kg |
Age |
ml |
mg |
ml |
mg |
| 5–8 |
3–11 months |
0.1–0.2 |
50–100 |
0.4–0.8 |
200–400 |
| 9–15 |
1–3 years |
0.2–0.5 |
100–250 |
0.8–2.0 |
400–1000 |
| 16–23 |
4–6 years |
0.3–0.8 |
150–400 |
1.2–3.2 |
600–1600 |
| 24–30 |
7–9 years |
0.4–1.0 |
200–500 |
1.6–4.0 |
800–2000 |
| 31–45 |
10–12 years |
0.5–1.4 |
250–700 |
2.0–5.6 |
1000–2800 |
| 46–53 |
13–14 years |
0.8–1.8 |
400–900 |
3.2–7.2 |
1600–3600 |
| > 53 |
≥ 15 years |
1.0–2.0* |
500–1000* |
4.0–8.0* |
2000–4000* |
* If necessary, the single dose can be increased to 5 mL (corresponding to 2500 mg of metamizole), and the daily dose – to 10 mL (corresponding to 5000 mg of metamizole).
Children.
Children should be administered the drug under medical supervision and only for serious or life-threatening conditions.
Overdose.
Symptoms: hypothermia, pronounced decrease in arterial blood pressure, palpitations, dyspnea, tinnitus, nausea, vomiting, gastralgia, weakness, oliguria, anuria, drowsiness, delirium, impaired consciousness, tachycardia, convulsive syndrome; acute agranulocytosis, hemorrhagic syndrome, acute renal and hepatic failure, and respiratory muscle paralysis may develop.
Treatment: induction of vomiting, gastric lavage via tube, 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.
Adverse reactions.
Hepatobiliary system disorders: hepatitis; drug-induced liver injury, including acute hepatitis, jaundice, increased liver enzyme levels (see section "Special precautions for use") – frequency unknown.
Urinary system disorders: oliguria, anuria, proteinuria, interstitial nephritis, red discoloration of urine.
Cardiovascular system disorders: hypotension, tachycardia.
Blood and lymphatic system disorders: agranulocytosis, leukopenia, thrombocytopenia, anemia, granulocytopenia.
Immune system disorders: hypersensitivity reactions, including skin and mucous membrane rashes, skin hyperemia, pruritus, urticaria, conjunctivitis, Quincke's edema; rarely – Stevens-Johnson syndrome, Lyell's syndrome, bronchospastic syndrome, anaphylactoid reactions, anaphylactic shock.
Skin and subcutaneous tissue disorders: drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) – frequency unknown.
General disorders and administration site conditions: infiltration at injection site (with intramuscular administration), hyperemia, swelling, local skin rashes and pruritus at injection site.
Shelf life. 2 years.
Storage conditions.
Store at a temperature not exceeding 25 °C in the original packaging. Do not freeze. Keep out of reach of children.
Incompatibility.
Due to a high probability of pharmaceutical incompatibility, the drug must not be mixed with other medicinal products in the same syringe.
Packaging.
2 ml in a vial; 5 vials in a blister pack; 2 blister packs in a carton.
Prescription status.
Prescription only.
Manufacturer.
LLC "Yuria-Pharm".
Manufacturer's address and location of business activity.
108, Kobzarska St., Cherkasy, 18030, Cherkasy region, Ukraine. Tel.: (044) 281-01-01.