Trinalgine (Solution) Instructions for Use

Marketing Authorization Holder

Biosintez, PJSC (Russia)

ATC Code

N02BB52 (Metamizole sodium in combination with other drugs, excluding psycholeptics)

Active Substances

Metamizole sodium (Rec.INN registered by WHO)

Pitofenone (Rec.INN registered by WHO)

Fenpiverinium bromide (Rec.INN registered by WHO)

Dosage Form

Trinalgine

Solution for intravenous and intramuscular administration 500 mg+2 mg+0.02 mg: 2 ml or 5 ml amp. 5 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration white in color, round, flat, with beveled edges and a dividing groove.

Excipients: sodium disulfite – 1 mg, 2M sodium hydroxide solution – sufficient quantity to adjust pH to 6.0-7.5, water for injection – up to 1 ml.

2 ml – ampoules of light-protective glass (10) – cardboard boxes.
2 ml – ampoules of light-protective glass (5) – contour cell packs made of polyvinyl chloride film (1) – cardboard packs.
2 ml – ampoules of light-protective glass (5) – contour cell packs made of polyvinyl chloride film (2) – cardboard packs.
5 ml – ampoules of light-protective glass (5) – contour cell packs made of polyvinyl chloride film (1) – cardboard packs.
5 ml – ampoules of light-protective glass (5) – contour cell packs made of polyvinyl chloride film (2) – cardboard packs.

Clinical-Pharmacological Group

Spasm analgesic

Pharmacotherapeutic Group

Non-narcotic analgesic agent (non-narcotic analgesic + spasmolytic)

Pharmacological Action

Combined analgesic and spasmolytic agent. The combination of the components of the agent leads to mutual enhancement of their pharmacological action.

Metamizole sodium – a pyrazolone derivative, has analgesic, antipyretic and weak anti-inflammatory action, the mechanism of which is associated with inhibition of prostaglandin synthesis.

Pitofenone hydrochloride has a direct myotropic effect on the smooth muscles of internal organs and causes its relaxation (papaverine-like action).

Fenpiverinium bromide has an m-cholinolytic action and exerts an additional myotropic effect on smooth muscles.

Pharmacokinetics

Metamizole sodium

After parenteral administration, unchanged Metamizole sodium is not detected in the blood (only after intravenous administration it is detected in blood plasma in a low concentration and quickly becomes undetectable). After intramuscular administration, the active substances of the agent are rapidly and substantially absorbed from the injection site.

Plasma protein binding is 50-60%. When used in therapeutic doses, it is excreted in breast milk.

Metamizole sodium undergoes intensive biotransformation in the liver. The main metabolites are 4-methylaminoantipyrine, 4-formylaminoantipyrine, 4-aminoantipyrine and 4-acetylaminoantipyrine. About 20 additional metabolites have been identified, including glucuronic acid derivatives. The main four metabolites are found in the cerebrospinal fluid. It is excreted mainly by the kidneys.

Pitofenone

It is rapidly distributed in organs and tissues, does not penetrate the blood-brain barrier.

It is metabolized in the liver by oxidative reactions. It is excreted in the urine. T_1/2 is 1.8 h.

Fenpiverinium bromide

It does not penetrate the blood-brain barrier. It is excreted unchanged in the urine 32.4-40.4%, in the bile – 2.3-5.3%.

Indications

Pain syndrome (mild or moderate) in spasms of smooth muscles of internal organs: renal colic, spasm of the ureter and bladder; biliary colic; biliary dyskinesia; postcholecystectomy syndrome; intestinal colic; chronic colitis; algodysmenorrhea; diseases of the pelvic organs.

For short-term treatment of arthralgia; myalgia; neuralgia, sciatica.

As an auxiliary medicinal agent for pain syndrome after surgical interventions and diagnostic procedures.

ICD codes

Dosage Regimen

It is administered intramuscularly and intravenously. For adults and adolescents over 15 years of age with acute severe colic, administer 2 ml intravenously slowly (1 ml per 1 min); if necessary, repeat after 6-8 hours. Intramuscularly – 2-5 ml of solution 2-3 times/day. The maximum daily dose should not exceed 10 ml (which corresponds to 5 g of sodium metamizole).

The duration of the treatment course is determined depending on the clinical symptoms and etiopathogenesis of the disease, but should not exceed 5 days.

Dosage calculation for children for intravenous and intramuscular administration: 3-11 months (5-8 kg) – intramuscularly only – 0.1-0.2 ml; 1-2 years (9-15 kg) – intravenous – 0.1-0.2 ml, intramuscular – 0.2-0.3 ml; 3-4 years (16-23 kg) – intravenous – 0.2-0.3, intramuscular – 0.3-0.4 ml; 5-7 years (24-30 kg) – intravenous – 0.3-0.4 ml, intramuscular – 0.4-0.5 ml; 8-12 years (31-45 kg) – intravenous – 0.5-0.6 ml, intramuscular – 0.6-0.7 ml; 12-15 years – intravenous and intramuscular – 0.8-1 ml.

Before administration, the injection solution should be warmed in the hand.

Adverse Reactions

Allergic reactions urticaria (including on the conjunctiva and mucous membranes of the nasopharynx), angioedema, rarely – malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), bronchospasm, anaphylactic shock.

From the hematopoietic system thrombocytopenia, leukopenia, agranulocytosis (may manifest with the following symptoms: unmotivated fever, chills, sore throat, difficulty swallowing, stomatitis, as well as the development of vaginitis or proctitis).

From the cardiovascular system decrease in blood pressure.

From the urinary system impaired renal function, oliguria, anuria, proteinuria, interstitial nephritis, red coloration of urine.

Anticholinergic effects dry mouth, decreased sweating, accommodation paresis, tachycardia, difficult urination.

Local reactions with intramuscular administration, infiltrates at the injection site are possible.

Contraindications

Hypersensitivity (including to pyrazolone derivatives); severe hepatic and/or renal impairment; bone marrow depression; glucose-6-phosphate dehydrogenase deficiency; tachyarrhythmia; severe angina pectoris; decompensated chronic heart failure; collapse; angle-closure glaucoma; prostatic hyperplasia (with clinical manifestations); intestinal obstruction; megacolon; pregnancy (especially the first trimester and the last 6 weeks); lactation period (breastfeeding); children under 3 months of age or body weight less than 5 kg (for intravenous administration).

With caution renal/hepatic impairment; bronchial asthma; tendency to arterial hypotension; hypersensitivity to NSAIDs; urticaria or acute rhinitis provoked by acetylsalicylic acid or other NSAIDs.

Use in Pregnancy and Lactation

The use of the agent is contraindicated during pregnancy (especially in the first trimester and the last 6 weeks).

If it is necessary to use the agent during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

The use of the agent is contraindicated in severe hepatic impairment.

The agent should be prescribed with caution in hepatic impairment.

Use in Renal Impairment

The use of the agent is contraindicated in severe renal impairment.

The agent should be prescribed with caution in renal impairment.

Pediatric Use

Intravenous administration of the agent is contraindicated in children under 3 months of age or with body weight less than 5 kg. The agent should be used for the treatment of children under 5 years of age only under medical supervision.

Special Precautions

With long-term (more than a week) treatment, monitoring of the peripheral blood picture and functional state of the liver is necessary.

If agranulocytosis is suspected or if thrombocytopenia is present, the use of the agent should be discontinued.

The use of the agent to relieve acute abdominal pain is unacceptable until the cause of the disease is clarified.

Intolerance is very rare, however, the threat of anaphylactic shock after intravenous administration of the agent is relatively higher than after oral administration.

Patients with atopic bronchial asthma and hay fever have an increased risk of developing allergic reactions.

Parenteral administration of the agent should be used only in cases where oral administration is impossible or absorption from the gastrointestinal tract is impaired.

Intravenous injection should be performed slowly, with the patient in a lying position and under the control of blood pressure, heart rate and respiratory rate.

Special care must be taken when administering more than 2 ml of solution (there is a risk of a sharp decrease in blood pressure).

For intramuscular administration, a long needle must be used.

When treating children under 5 years of age and patients receiving cytostatics, the use of sodium metamizole should be carried out only under medical supervision.

Red coloration of urine is possible due to the excretion of a metabolite (of no clinical significance).

During treatment with the agent, it is not recommended to take ethanol.

Effect on the ability to drive vehicles and machinery

During the use of the agent, patients should exercise caution when driving vehicles and machinery, as well as when engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Histamine H₁-receptor blockers, butyrophenones, phenothiazines, tricyclic antidepressants, amantadine and quinidine – possible enhancement of m-cholinolytic action.

Chlorpromazine or other phenothiazine derivatives – possible development of severe hyperthermia.

Non-narcotic analgesics, tricyclic antidepressants, oral hormonal contraceptives and allopurinol – increase the toxicity of the agent.

Phenylbutazone, barbiturates and other inducers of microsomal enzymes – reduction of the effectiveness of sodium metamizole.

Sedatives and anxiolytics (tranquilizers) – enhancement of the analgesic effect of sodium metamizole.

Radiocontrast agents, colloidal blood substitutes and penicillin – combinations with drugs containing Metamizole sodium should not be used.

Cyclosporine – possible decrease in the concentration of cyclosporine in the blood.

Oral hypoglycemic agents, indirect anticoagulants, corticosteroids and indomethacin – Metamizole sodium displaces these agents from protein binding, which may lead to an increase in the severity of their action.

Thiamazole and cytostatics – increased risk of leukopenia.

Medicinal products with myelotoxic action enhancement of the hematotoxic effect of the agent.

Codeine, histamine H₂-receptor blockers, propranolol – enhancement of the action of the agent due to slowing down the inactivation of sodium metamizole.

Ethanol – enhancement of the effects of ethanol.

The injection solution is pharmaceutically incompatible with other medicinal products.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.