Pixalzina

Warnings and precautions

Before starting to take Pixalzina, you should discuss it with your doctor or pharmacist:

• asthma with concurrent rhinitis.
• prolonged and/or chronic urticaria.
• intolerance or hypersensitivity to dyes (e.g., tartrazine) or preservatives (e.g., benzoates).
• alcohol intolerance, i.e., patients who react to even small amounts of alcohol with sneezing, tearing, and pronounced facial flushing.

Agranulocytosis (a very low number of a certain type of white blood cell called granulocytes, which play an important role in fighting infections) may occur. If you experience any of the following symptoms, which may indicate possible agranulocytosis, you should stop taking metamizole and immediately contact your doctor: chills, fever, sore throat, and painful ulcers on the mucous membranes, especially in the mouth, nose, and throat or in the genital or anal area. Your doctor will order a laboratory test to check your blood cell count.
If metamizole is taken for fever, some symptoms of developing agranulocytosis may remain unnoticed. Similarly, symptoms may also be masked if the patient is taking antibiotics.
Agranulocytosis may develop at any time during Pixalzina treatment and even for a short time after stopping metamizole treatment.
Agranulocytosis may occur even if metamizole was previously administered without complications.
Liver disorders
Patients taking metamizole have experienced cases of hepatitis, whose symptoms appeared within a few days to a few months after starting treatment.
You should stop taking Pixalzina and contact your doctor if you experience any liver disorders, such as: malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, light-colored stools, yellowing of the skin or whites of the eyes, itching, rash, or pain in the upper abdomen. Your doctor will check your liver function.
You should not take Pixalzina if you have previously taken any medicines containing metamizole and had liver disorders.
Severe skin reactions
Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with metamizole treatment. If you experience any of these symptoms of severe skin reactions, you should stop taking metamizole and seek medical attention immediately.
If you have ever had severe skin reactions, you should never take Pixalzina again (see section 4).

Pixalzina and other medicines

You should tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take, especially:

• methotrexate (a medicine used to treat cancer or certain rheumatic diseases). Concomitant use may increase the potential risk of blood cell damage by methotrexate, especially in elderly patients. Concomitant use of these medicines should be avoided.
• acetylsalicylic acid (aspirin). Metamizole may reduce its effect on blood platelets. Pixalzina should be used with caution when administered with low doses of acetylsalicylic acid for heart protection. Metamizole may weaken the effect of medicines such as:
• cyclosporine (a medicine that suppresses the immune system).
• efavirenz (a medicine used to treat HIV/AIDS).
• methadone (a medicine used to treat opioid addiction).
• valproate (a medicine used to treat epilepsy or bipolar disorder).
• tacrolimus (a medicine used to prevent organ rejection in patients after transplantation).
• sertraline (a medicine used to treat depression).
• bupropion (a medicine used to treat depression or as an aid to smoking cessation). Your doctor will closely monitor your condition if metamizole is administered concomitantly with any of these medicines.

Taking Pixalzina with alcohol

You should not consume alcohol while taking Pixalzina.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a child, you should consult your doctor or pharmacist before taking this medicine.
Pregnancy
Metamizole should not be used during the first 6 months of pregnancy. Available data on the use of metamizole during the first 3 months of pregnancy are limited but do not indicate harmful effects on the fetus. In selected cases, if there are no other treatment options, after consulting a doctor or pharmacist, the patient may take single doses of metamizole in the first and second trimester of pregnancy, provided that the benefits and risks associated with taking the medicine are carefully weighed.
Metamizole should not be taken during the last 3 months of pregnancy due to the increased risk of complications in the mother and child (bleeding, premature closure of the ductus arteriosus in the child, which normally closes only after birth).
Breastfeeding
Metamizole should not be taken during repeated breastfeeding. Metamizole metabolites pass into breast milk in significant amounts, and the risk to the breastfed infant cannot be excluded. In the case of single administration of metamizole, mothers should be advised to discard and pour away breast milk for 48 hours after administration of the medicine.

Driving and using machines

Within the recommended dose range, no adverse effects have been observed that affect the ability to react and concentrate.
However, as a precaution, especially when taking higher doses, the possibility of impaired ability to react and concentrate should be considered, and operating machines, driving vehicles, or performing activities that involve risk should be avoided. This applies especially to concomitant use with alcohol.

Pixalzina contains sodium

This medicine contains 32.7 mg of sodium (a major component of table salt) in 1 ml of solution for injection/infusion, which corresponds to 1.6% of the maximum recommended daily intake of sodium in the diet for adults.

3. How to take Pixalzina

This medicine should always be taken according to the doctor's or pharmacist's recommendations. If you have any doubts, you should consult your doctor or pharmacist.
The dose depends on the severity of the pain or fever and the individual's sensitivity to Pixalzina. Pixalzina will be injected into a vein or muscle (intravenous or intramuscular administration).
The onset of the medicine's effect can be expected after 30 minutes of administration, and the duration of action is usually about 4 hours.
If the analgesic effect after a single dose of the medicine is insufficient or if the effect wears off after some time, the doctor may administer another dose, not exceeding the maximum daily dose described below.
During administration (injection), you should remain in a lying position and under the doctor's supervision to properly monitor your condition.

Recommended doses

Use in adults and adolescents over 15 years old
Adults and adolescents over 15 years old (with a body weight over 53 kg) may receive a single dose of 1-2 ml administered intravenously (into a vein) or intramuscularly (into a muscle); if necessary, the single dose may be increased to a maximum of 5 ml (corresponding to 2500 mg of metamizole). The maximum daily dose is 8 ml; if necessary, the daily dose may be increased to a maximum of 10 ml (corresponding to 5000 mg of metamizole).
Use in children
You should follow the dosing schedule below for single intravenous or intramuscular doses:
Older adults and patients in poor general health or with impaired renal function
In older adults, weakened patients, and patients with impaired renal function, the dose should be reduced due to the possibility of prolonged elimination of metamizole metabolites.
Patients with impaired renal or hepatic function
Due to reduced elimination in patients with impaired renal or hepatic function, multiple high doses should be avoided. In the case of short-term use, dose reduction is not required. There is a lack of experience with long-term use.

Overdose of Pixalzina

In case of overdose, you should immediately contact your doctor to take appropriate actions.
Symptoms of overdose are nausea (vomiting), vomiting, abdominal pain, kidney problems, and less frequently, disorders of the nervous system (dizziness, drowsiness, loss of consciousness, convulsions). Severe overdose can also lead to a decrease in blood pressure (sometimes to shock) and increased heart rate.

At very high doses, a harmless metabolite may be excreted, causing a red discoloration of the urine, which disappears after stopping treatment.

Missing a dose of Pixalzina

You should not take a double dose to make up for a missed dose.
If you have any further doubts about taking this medicine, you should consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, Pixalzina can cause side effects, although not everybody gets them.

The following side effects may have serious consequences; you should stop taking Pixalzina and immediately inform your doctor:

If any of these side effects occur suddenly or worsen, you should immediately inform your doctor, as some reactions to the medicine (e.g., severe hypersensitivity reactions, severe skin reactions, such as Stevens-Johnson syndrome or toxic epidermal necrolysis, agranulocytosis, pancytopenia) can be life-threatening in certain situations. In such cases, you should never take Pixalzina again without medical supervision. Immediate discontinuation of treatment is crucial for recovery.

• Hypersensitivity reactions (anaphylactoid or anaphylactic reactions) - rare side effects. Typical symptoms of mild reactions include: burning eyes, cough, nasal symptoms, nasal congestion, sneezing, chest pain, facial flushing (especially on the face and head), urticaria, and facial edema, and less frequently: nausea and stomach cramps. Specific warning signs are burning, itching, and a feeling of heat on and under the tongue, and especially on the palms and soles. Such mild reactions can progress to more severe forms with severe urticaria, severe angioedema (also in the larynx), severe bronchospasm (spastic narrowing of the airways), increased heart rate (sometimes decreased heart rate), arrhythmias, decreased blood pressure (sometimes preceded by an increase), loss of consciousness, and circulatory failure. These reactions can occur despite previous use of the medicine without complications and can be life-threatening, and in some cases, may lead to death. In patients with analgetic asthma syndrome, hypersensitivity reactions usually manifest as asthma attacks (see section 2 "When not to take Pixalzina").
• Red, flat spots on the torso in a target shape or round, often with blisters in the center, peeling skin, ulcers in the mouth, throat, nose, or genital or anal area. The occurrence of such severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome or toxic epidermal necrolysis) - frequency not known.
• Widespread rash, high body temperature, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
• Malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, light-colored stools, yellowing of the skin or whites of the eyes, itching, rash, or pain in the upper abdomen. These may be symptoms of liver damage. See also section 2 "Warnings and precautions".
• Significant decrease in the number of granulocytes - specific white blood cells (agranulocytosis), including cases with a fatal outcome, or decrease in the number of platelets (thrombocytopenia) - rare side effects. These reactions are likely to be immune-mediated. They may also occur when metamizole was previously administered without complications. If symptoms of agranulocytosis, pancytopenia

or thrombocytopenia (see below and section 2 "Warnings and precautions") occur, you should immediately stop taking Pixalzina, without waiting for the results of laboratory diagnostic tests. Blood morphology (including differential blood count) must be monitored by your doctor.
You should not take Pixalzina if you experience any of the following symptoms, which may indicate possible agranulocytosis:

• Unexpected worsening of your general condition (e.g., fever, chills, sore throat, difficulty swallowing).
• If the fever does not decrease or recurs.
• If painful changes occur on the mucous membranes, especially in the mouth, nose, and throat or in the genital or anal area. Typical symptoms of decreased platelet count include increased bleeding tendency and petechiae (spot bleeding) on the skin and mucous membranes. Decreased blood volume with accompanying bone marrow disorders (aplastic anemia), decreased number of white and red blood cells, and platelets (pancytopenia), including cases with a fatal outcome. Symptoms of pancytopenia and aplastic anemia include general malaise (weakness), infections, persistent fever, bruising, bleeding, and pallor.

Other possible side effects

Uncommon side effects (may occur in up to 1 in 100 people)

• Decrease in blood pressure (isolated hypotensive reaction), probably caused by the direct effect of the medicine and not accompanied by other hypersensitivity symptoms. Such a reaction causes a significant decrease in blood pressure only in rare cases. This risk may also be increased in patients with very high fever. Typical symptoms of severe hypotension include increased heart rate, pallor, trembling, dizziness, nausea, and loss of consciousness.

Rare side effects (may occur in up to 1 in 1,000 people)

• Decrease in the number of white blood cells (leukopenia) or red blood cells (aplastic anemia).
• Skin rash.

Very rare side effects (may occur in up to 1 in 10,000 people)

• Impaired kidney function, in some cases with reduced or absent urine output (oliguria or anuria), proteinuria, or acute kidney failure.

Frequency not known (frequency cannot be estimated from available data)

• Myocardial infarction in the course of an allergic reaction(Kounis syndrome),
• Gastrointestinal bleeding.
• Hepatitis, jaundice, and increased liver enzyme activity in the blood.
• Purple to dark red skin rash, sometimes with blisters (fixed drug eruption)
• Kidney failure (acute interstitial nephritis).
• Pain and local reactions at the injection site, phlebitis (vein inflammation)

Reporting side effects

If you experience any side effects, including those not listed in this leaflet, you should tell your doctor or pharmacist.
Side effects can be reported directly to the Department of Drug Safety Monitoring
Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Jerozolimskie Avenue 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pixalzina

The medicine should be stored out of sight and reach of children.
Store in a temperature below 25 °C. Store in the original packaging to protect from light.
Do not use this medicine after the expiration date stated on the packaging after the term EXP. The expiration date refers to the last day of the specified month.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Pixalzina contains

• The active substance of Pixalzina is metamizole sodium monohydrate. 1 ml of solution for injection contains 500 mg of metamizole sodium monohydrate. One ampoule of 2 ml of solution for injection contains 1000 mg of metamizole sodium monohydrate. One ampoule of 5 ml of solution for injection contains 2500 mg of metamizole sodium monohydrate.
• Other ingredients are: sulfuric acid 10%, water for injections.

What Pixalzina looks like and contents of the packaging

Pixalzina is a clear, colorless to slightly yellowish solution. It does not contain visible particles.
Brown ampoule with a capacity of 2 ml made of borosilicate glass, with a neutral hydrolytic resistance of type I, marked with a gray break point and 2 green identification rings, contains 2 ml of Pixalzina.
Brown ampoule with a capacity of 5 ml made of borosilicate glass, with a neutral hydrolytic resistance of type I, marked with a gray break point and 2 green identification rings, contains 5 ml of Pixalzina.
Ampoules of Pixalzina with a capacity of 2 ml are available in packs of 5, 10, 100 ampoules.
Ampoules of Pixalzina with a capacity of 5 ml are available in packs of 5, 10 ampoules.
Not all pack sizes may be marketed.

Marketing authorization holder

Zentiva, k.s.
U kabelovny 130
Dolní Měcholupy
102 37 Prague 10
Czech Republic

Manufacturer

Zentiva S.A.
B-dul Theodor Pallady nr. 50, sector 3
032266 Bucharest
Romania
To obtain more detailed information about this medicine, you should contact the local representative of the marketing authorization holder:
Zentiva Polska Sp. z o.o.
Bonifraterska Street 17
00-203 Warsaw
phone: +48 22 375 92 00

This medicine is authorized in the Member States of the European Economic Area under the following names:

Czech Republic: Afexil
Austria: Metamizol Zentiva
Poland: Pixalzina
Slovakia: Nofebran
Date of last revision of the leaflet:April 2025
Information intended for healthcare professionals only:
Parenteral administration of the medicine is associated with a high risk of anaphylactic or anaphylactoid reactions.
It should be ensured that the injection of the medicine is discontinued after the appearance of the first signs of an anaphylactic or anaphylactoid reaction, and that the risk of isolated hypotensive reaction is minimized. During parenteral administration, the patient should be in a lying position and under close medical supervision. Furthermore, to prevent the occurrence of hypotensive reactions, intravenous administration should be performed very slowly, i.e., no more than 1 ml (500 mg of metamizole) per minute.
The solution for injection can be diluted using a 5% glucose solution (50 mg/ml), 0.9% sodium chloride solution (9 mg/ml), or Ringer's solution. The mixture should be administered immediately after preparation due to its limited stability. Due to possible pharmaceutical incompatibilities of the metamizole solution, it should not be administered together with other injectable medicines