Active substance: Metamizole sodium monohydrate 2500 mg, Pitofenone hydrochloride 10 mg, Fenpiverimium bromide 0.1 mg in 5 ml. 

For a full list of excipients, see section 6.1.

Solution for injection 

Clear, colorless to slightly yellowish solution

It is indicated for the treatment of colicky pain in biliary and urinary tract, bladder tenesmus, painful spasms in the stomach and intestines, spastic dysmenorrhea, and control of spastic pain during and after instrumental examination. 

4.2 Posology and method of administration 

a) Dosage for children: 

Infants under 4 months – Analgin should not be administered. 

From 4-12 months are given a single dose of 0.2 to 0.3 ml. 

Young children (1-6 years) are administered 0.3 to 0.5 ml. 

School age children (7-12 years) are administerd 0.6 - 1 ml. 

b) Dosage for adults: 

Adults are given a single dose of up to 5 ml. 

Injection shall be warmed up to body temperature before application. Intravenous solution must be administered very slowly (1-1.5 ml per minute)in lying patient. Rapid intravenous administration causes a sharp drop in pressure and shock. The initial dose should not be higher than 2 ml solution for injection. If necessary, the dose could be increased progressively up to 5 ml. During application the blood pressure, pulse and respiratory rate must be monitored. The dose may be repeated after 6-8 hours. The daily dose should not exceed 10 ml. 

Hypersensitivity to any of the ingredients, especially to the pyrazolon derivatives, leukopenia, pregnancy and lactation, children under the age of 4 months, acute intermittent porphyria, prostatic hypertrophy, glaucoma, severe cardiac insufficiency, recent myocardial infarction, tachycardia, mechanical stenosis of the gastrointestinal tract, megacolon. 

Owing to the content of pyrazolon, especially after repeated, prolonged administration, hematopoietic disorders may appear. Their emergence may predispose patients with primary hematopoietic disorders and treated with chemotherapy.The production of leukocytes and platelets is mainly affected. Therefore during the treatment with the preparation is necessary to monitor clinically and to examine laboratory the possibility of such adverse reaction. 

Particular attention should be paid to patients with low blood pressure, circulatory instability and failing circulation in myocardial infarction, in polytrauma and in developing shock. Development of asthma attacks or anaphylactic shock are risk for patients with a history of asthma provoced by NSAIDs, chronic urticaria, or rhinitis. Listed adverse reactions can be prevented thorough drug history. 

The preparation may adversely affect attention, physical coordination and responsible decisions when driving or operating machinery and working at heights etc.

Metamizol when administered with cyclosporine can reduce its plasma level. It is inappropriate co-administer anticoagulants, oral antidiabetic agents, sulfonamides, and substances that cause blood dyscrasias. During the treatment with ANALGIN it is not recommended to consume alcoholic beverages, because alcohol effect is potentiated. 

4.6 Pregnancy and lactation 

Administration of ANALGIN in the first trimester of pregnancy is not recommended (potential teratogenicity). In the last trimester may cause premature closure of the ductus arteriosus Bottali. Metamizol crosses the placenta. 

Its metabolites are excreted in breast milk. Therefore during the first 48 hours after administration of metamizol the mother should not breastfeed. 

Analgin has minor or moderate influence on the ability to drive or operate machinery. 

  

4.8 Undesirable effects 

The serious adverse reactions after administration might include a shock. Signs of the starting shock are cold sweat, dizziness, nausea, skin discoloration, shallow breathing. It is accompanied by precordial tightness, rapid pulse, cold extremities and a sharp drop in blood pressure. Immediately after the onset of first symptoms the administration should be discontinued and the intense shock therapy must be applied. 

Another serious side effect is blood dyscrasias (agranulocytosis, leukopenia, thrombocytopenia). 

Agranulocytosis is associated with fever, painful lesions of mucous membranes of the mouth, throat, nose, but also in the area of rectum and genitals. The number of granulocytes is significantly reduced or completely absent. Erythrocytes and hemoglobin are not changed. Thrombocytopenia after metamizol causes increased bleeding. There is a threat to those with pre-existing disorders of hematopoiesis. The reaction has the character of antigen-antibody immune response, where the drug enters the interaction with white blood target cells.

During the fast application especially in patients with high fever it might cause a sharp drop in blood pressure. The risk is higher in hypotonic patients and people with unstable circulation. Metamizol allergy may be manifested by skin or mucosal eruptions. Metamizol in sensitive patients may provoke an asthma attack. 

Anticholinergic ingredient - fenpiverinium can cause dry mouth, accommodation disorders, constipation, difficulty urinating, faster pulse rate. 

4.9. Overdose 

Symptoms: In the experimental conditions are manifested by acute tachypnoea, sedation and analgesia. In animals affected by the lethal dose convulsions appear before death. Parenteral administration of the lethal dose induces death of animals within 1 hour after application. Oral administration leads to death of animals within one day. 

According to therapeutic breadth the overdose is rare. Acute poisoning by metamizole has a milder course than by other pyrazolones. The literature presents acute poisoning with suicidal attempt with 49 g metamizole, the patient has survived. 

When poisoning occurs, dizziness, feelings of gloom, epileptiform conditions, paralysis, respiratory and circulatory collapse, blurred consciousness, somnolence and coma appear. In mild cases from face redness, dryness of mucous membranes, tachycardia, mydriasis, urinary retention, motoric restlessness, increase in body temperature, to the state of exhaustion and sleepiness occur. Poisoning is accompanied by disturbances of cardiac rhythm and contractility. 

Treatment: Treatment of overdose is symptomatic procedure used to preserve the vital functions. It is necessary to ensure adequate ventilation. Theophylline products and analeptics are contraindicated. During the circulatory collapse it is necessary to supplement the blood volume and cardiac function can be supported by infusion of dopamine. Seizures are treated by intravenously administered diazepam. Metamizole is eliminated by hemodialysis and by hemoperfusion. 

Pharmacotherapeutic group 

Analgesic with spasmolytic component. 

ATC code: A03DA02 

Mechanism of action 

The exact mechanism and location of action of metamizol are not explained in detail. It is assumed that it operates in a combined central and peripheral effects. The central action is explained by inhibition of prostaglandin synthesis, secretion of histamine and serotonin from mast cells of thalamus. Peripheral effect is explained by the inhibition of prostaglandin synthesis which sensitize nociceptors to the effect of algogen mediators. In addition, metamizol has a direct blocking effect on the inflammatory hyperalgesia. Pitofenon hydrochloride is a substance similar to papaverine, acting as a spasmolytic, directly on smooth muscle cells. Fenpiverinium bromide is parasympatholytic, which relaxes smooth muscle spasms due to anticholinergic effect on the parasympathetic endings and weak ganglioplegic effect on nerve impulses in the synapses of the vegetative nervous system. 

The product combines the analgesic effects of metamizol and spazmolytic effects of pitofenon and fenpiverine. The result is spasmoanalgesic effect. 

5.2 Pharmacokinetic properties 

After intravenous administration unchanged metamizol in the plasma can be proved only for a short time, because it is quickly hydrolysed to 4-methylaminoantipyrine (4-MAA). After oral administration the bioavailability is 85%, after rectal administration is 54%. The peak concentration in plasma reaches in 1.2 - 2 hours. Plasma protein binds approximately 60% of metamizol and its metabolites. Distribution volume is about 1,15 l / kg. After a slow intravenous administration the effect starts after 8 minutes, sometimes during the time when injection is administered. The effect usually takes longer than 5 hours. 

4-MAA is metabolised in the liver to 4-formylaminoantipyrine and to 4-aminoantipyrine (4-AA), which is further metabolized to 4-acetylaminoantipyrine. 4-MAA and 4-AA is the effective analgesic. Elimination half-life of 4-AA is in extensive metabolisers 3.8 hours and 5.5 hours in slow metabolisers. Maximum amount of metamizol is excreted in urine in the first 24 hours. Within 7 days after i.v. application 96% of administered dose is eliminated. Plasma protein binds about 58% of the main metabolite 4-MAA. 

Studies in children from 1 to 11 years, where metamizole was used for therapeutic reasons showed faster elimination in comparison with adults, which is explained by accelerated biotransformation.In geriatric healthy volunteers (73-90 year old) was significantly prolonged half-life and reduced total clearance of 4-MAA. 

In the third trimester of pregnancy the excretion of metamizole is reduced and the half-life is prolonged. The reason is the reduced capacity of biotransformation. Concentration in breast milk correlates with plasma levels of metabolites. 48 hours after a single dose, there is not any metabolite in the breast milk. 

In patients with chronic renal insufficiency half-life of 4-MAA is prolonged, the total and renal clearance are prolonged as well. 

Patients with cirrhosis, steatosis, chronic hepatitis have a reduced excretion of metabolites and the prolonged elimination of metamizol. 

As a result of inefficient elimination of metamizol metabolites - rubazone acid, urine turns red. 

Preclinical data based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity and reproductive toxicity studies reveal no special hazard for humans. 

Water for Injections 

Sodium content in the product: 32.7 mg / ml, corresponding to 1.423 mmol / ml. 

Product is incompatible with indigo, therefore, should not be mixed in one syringe. 

6.3 Shelf life 

3 years

Store at temperatures between +10 ° C to +25 ° C, in original packaging. 

6.5 Nature and contents of container 

Ampoules of brown glass with a label, insert PVC box. 

Package Size: 5 ampoules 5 ml

Any unused product or waste material should be disposed of in accordance with local requirements. 

BB Pharma Pod Višňovkou 1662/21, 140 00 Prague 4, Czech Republic 

73/760/92-S/C

 December 14th, 1992

November 16th, 2005