Piralgina Plus

Leaflet accompanying the packaging: patient information

PYRALGINA PLUS, 400 mg + 60 mg + 40 mg, coated tablets

Metamizole sodium + Caffeine + Drotaverine hydrochloride
The Pyralgina Plus medicine may cause an abnormally low number of white blood cells (agranulocytosis), which can lead to severe and life-threatening infections (see section 4).
You should stop taking the medicine and contact your doctor immediately if you experience any of the following symptoms: fever, chills, sore throat, painful ulcers in the nose, mouth and throat, or in the genital or anal area.
If the patient has ever had agranulocytosis while taking metamizole or similar medicines, they should never take this medicine again (see section 2).

You should carefully read the contents of the leaflet before taking the medicine, as it contains important information for the patient.

This medicine should always be taken exactly as described in this patient leaflet or as directed by your doctor or pharmacist.
You should keep this leaflet so that you can read it again if you need to.

• You should keep this leaflet so that you can read it again if you need to.
• If you need advice or additional information, you should consult your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, you should tell your doctor or pharmacist. See section 4.
• If you do not feel better or if you feel worse, you should contact your doctor.

Table of contents of the leaflet

• 1. What is Pyralgina Plus and what is it used for
• 2. Important information before taking Pyralgina Plus
• 3. How to take Pyralgina Plus
• 4. Possible side effects
• 5. How to store Pyralgina Plus
• 6. Contents of the packaging and other information

1. What is Pyralgina Plus and what is it used for

Pyralgina Plus is intended for use in adults for the symptomatic treatment of:

• pain of various origins with high intensity
• pains associated with smooth muscle spasms:
• urinary and reproductive system (renal colic, painful menstruation),
• gastrointestinal tract (intestinal colic, irritable bowel syndrome),
• bile ducts (cholecystitis, cholangitis), when the use of other medicines is contraindicated or ineffective.

Pyralgina Plus contains three active substances. Metamizole sodium has analgesic properties, and drotaverine hydrochloride has a spasmolytic effect on smooth muscles. Caffeine is an additive to many analgesic medicines.

2. Important information before taking Pyralgina Plus

When not to take Pyralgina Plus:

• if the patient has a history of significant reduction in the number of white blood cells called granulocytes caused by metamizole or other similar medicines called pyrazolones or pyrazolidines;
• if the patient has disorders of bone marrow function or a disease that affects the production or function of blood cells;
• if the patient is allergic to metamizole, caffeine, drotaverine, pyrazolone derivatives (e.g., phenazone, propyphenazone), or pyrazolidine derivatives (e.g., phenylbutazone, oxyphenbutazone), or any of the other ingredients of this medicine (listed in section 6);
• if the patient has asthma or intolerance associated with taking certain painkillers, such as salicylates, paracetamol, diclofenac, ibuprofen, indomethacin, or naproxen, manifested by, for example, bronchospasm, urticaria, rhinitis, or angioedema;
• if the patient has severe renal or hepatic impairment;
• if the patient has severe heart failure;
• if the patient has second- or third-degree atrioventricular block;
• if the patient has certain metabolic disorders (porphyria, glucose-6-phosphate dehydrogenase deficiency);
• if the patient has anemia;
• if the patient is under 18 years of age;
• if the patient is pregnant or breastfeeding;
• if the patient has a known hypersensitivity to soy or peanuts (the medicine contains soy lecithin).

Warnings and precautions

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

• if you have asthma or intolerance associated with taking certain painkillers (see "When not to take Pyralgina Plus" above) manifested by urticaria, angioedema, particularly if it is accompanied by nasal polyposis and sinusitis;
• if you have bronchial asthma, especially when accompanied by sinusitis and nasal polyps;
• if you have an allergy, atopy may lead to anaphylactic shock. Therefore, when using metamizole, special caution is recommended in patients with asthma or atopy (see also "When not to take Pyralgina Plus" above);
• if you have chronic urticaria;
• if you have intolerance to certain dyes (e.g., tartrazine) or preservatives (e.g., benzoates);
• if you have alcohol intolerance manifested by sneezing, tearing, and severe facial flushing in response to even small amounts of alcohol; this may indicate previously undiagnosed asthma associated with taking certain painkillers (see "When not to take Pyralgina Plus" above);
• if you have low blood pressure, circulation problems, have experienced fluid loss from the body, or have dehydration;
• if you have high blood pressure;
• if you have a high fever;
• if you have kidney or liver problems;
• if you are over 65 years of age, in poor general health, or have renal impairment;
• if you have hypersensitivity to other substances. In case of doubt whether the above circumstances apply to you, you should consult your doctor before starting to take Pyralgina Plus.

Agranulocytosis (abnormally low number of white blood cells)
Pyralgina Plus may cause agranulocytosis, a very low number of a certain type of white blood cells called granulocytes, which play an important role in fighting infections (see section 4). You should stop taking metamizole and contact your doctor immediately if you experience any of the following symptoms, as they may indicate possible agranulocytosis: chills, fever, sore throat, and painful ulcers of 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 the number of blood cells.
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 can develop at any time during the use of Pyralgina Plus, and even for a short time after stopping the use of metamizole.
Agranulocytosis can occur even if metamizole was previously administered without complications.
Abnormal number of platelets and other blood cells
Metamizole may cause thrombocytopenia, manifested by increased bleeding tendency, bleeding into the skin and mucous membranes. If symptoms of thrombocytopenia occur, the patient should immediately stop taking the medicine and contact their doctor.
During treatment, a serious decrease in the number of red and white blood cells, as well as platelets, called pancytopenia, may also occur. Patients should immediately consult a doctor if they experience symptoms such as malaise, infection, persistent fever, bruising, bleeding, or pallor. If a blood test shows deviations in the number of blood cells or platelets, treatment should be stopped immediately and the number of blood cells and platelets should be monitored until they return to normal.
Liver disorders
In patients taking metamizole, cases of hepatitis have occurred, with symptoms appearing within a few days to several months after starting treatment.
You should stop taking Pyralgina Plus and contact your doctor if you experience liver disorders, such as malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale stools, yellowing of the skin or whites of the eyes, itching, rash, or pain in the upper abdomen. Your doctor will check the liver function.
The patient should not take Pyralgina Plus if they have previously taken any medicinal products containing metamizole and had liver disorders.
Severe skin reactions
Severe skin reactions have been reported with metamizole, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS syndrome). If the patient experiences any of these symptoms of severe skin reactions mentioned in section 4, they should stop taking metamizole and seek medical attention immediately.
If the patient has ever experienced severe skin reactions, they should never take Pyralgina Plus again (see section 4).
Severe allergic reaction
A severe allergic reaction, known as anaphylactic reaction, is characterized by sudden onset of, for example, facial and throat edema, generalized urticaria, bronchospasm, and can be life-threatening. Therefore, Pyralgina Plus should not be taken by patients with hypersensitivity to the ingredients of this medicine or by patients with a history of allergic reactions to other painkillers (detailed description of contraindications can be found above in "When not to take Pyralgina Plus"). Patients who have had an anaphylactic reaction or other immunological reaction to metamizole are also at risk of a similar reaction to other pyrazolones and pyrazolidines.
Decrease in blood pressure
Pyralgina Plus may cause a decrease in blood pressure (hypotension), which is likely to be dose-dependent. The risk of severe hypotension increases in patients with previously low blood pressure, circulation problems, and in patients who have experienced fluid loss from the body or have dehydration (see above). In such patients, Pyralgina Plus should be used with caution and only after consulting a doctor.
Elderly patients
See section 3.
Patients with kidney or liver problems
See section 3.
Due to the caffeine contained in the medicine, you should avoid excessive consumption of caffeine (e.g., coffee, tea, and some other beverages) while taking this medicine.
The medicine should not be taken just before bedtime.

Children and adolescents

Pyralgina Plus should not be taken by patients under 18 years of age (see "When not to take Pyralgina Plus" in section 2).

Pyralgina Plus 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.
When taking Pyralgina Plus with other medicines, you should consider the following interactions:

• Cyclosporine(used in the treatment of patients after transplants) - the cyclosporine level in the serum should be monitored, as it may decrease due to the interaction with metamizole;
• Methotrexate(a medicine used in the treatment of certain types of cancer) - metamizole may increase the toxicity of methotrexate to the bone marrow (the site where new blood cells are produced), especially in elderly patients. Therefore, it is recommended to avoid concomitant use of methotrexate and Pyralgina Plus.
• Acetylsalicylic acid- metamizole may reduce the anti-aggregatory effect of low doses of acetylsalicylic acid. Patients taking low doses of acetylsalicylic acid for the prevention of heart disease should use Pyralgina Plus with caution.
• Bupropion(an antidepressant and a medicine used to help quit smoking) - metamizole may reduce the bupropion level in the blood. Therefore, caution is recommended when concomitantly using Pyralgina Plus and bupropion;
• Efavirenz(a medicine used in the treatment of HIV infection (AIDS)) - metamizole may reduce the level of this medicine in the plasma and limit its clinical effectiveness;
• Methadone(a medicine used in the treatment of opioid addiction) - metamizole may reduce the level of this medicine in the plasma and limit its clinical effectiveness;
• Valproate(a medicine used in the treatment of epilepsy or bipolar disorder)
• metamizole may reduce the level of this medicine in the plasma and limit its clinical effectiveness;
• Tacrolimus(a medicine used to prevent organ rejection in patients after transplantation)
• metamizole may reduce the level of this medicine in the plasma and limit its clinical effectiveness;
• Sertraline(a medicine used in the treatment of depression) - metamizole may reduce the level of this medicine in the plasma and limit its clinical effectiveness;
• Medicines metabolized by the liver(e.g., clarithromycin, ethinyl estradiol, sertraline) - caffeine may cause an increase in their blood levels.
• Salicylates- caffeine may increase their absorption.
• Cimetidine(a medicine that reduces the amount of acid in the stomach), oral contraceptives, ciprofloxacin and enoxacin(used in the treatment of infections), mexiletine(used in the treatment of heart rhythm disorders) - these medicines may increase the caffeine level in the blood;
• Muscle relaxants- some muscle relaxants block the metabolism of caffeine, so concomitant use of Pyralgina Plus with these medicines is not recommended;
• Nicotine- increases caffeine excretion;
• Disulfiram(used in the treatment of alcoholism), ethinyl estradiol(used in the treatment of menstrual disorders and as a contraceptive) - may increase the effect of caffeine;
• Levodopa(used in the symptomatic treatment of Parkinson's disease) - the effect of levodopa may be reduced, so when concomitantly using Pyralgina Plus and levodopa, tremors and stiffness may worsen in patients with Parkinson's disease.

Pyralgina Plus and alcohol

Concomitant consumption of alcohol may affect concentration and reaction time (see Driving and operating machinery).

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor or pharmacist before taking this medicine.
Do not take Pyralgina Plus during pregnancy and breastfeeding.

Driving and operating machinery

Within the recommended dose range, no effect of Pyralgina Plus on concentration and reaction time has been observed. However, in case of higher doses of metamizole or after consuming alcohol, concentration and reaction time may be impaired, or drotaverine may cause dizziness, and caffeine may cause psychomotor hyperactivity and nervousness or fatigue, which can pose a risk in situations where they are particularly important (e.g., when driving vehicles and operating machinery).

The medicine contains lactose monohydrate, sodium, and soy lecithin

Pyralgina Plus contains lactose monohydrate

If you have been diagnosed with intolerance to some sugars, you should consult your doctor before taking the medicine.

Pyralgina Plus contains sodium

Each coated tablet contains 27.6 mg of sodium (the main component of common salt) per tablet, which corresponds to 1.4% of the WHO-recommended maximum daily intake of 2 g of sodium for adults.

Pyralgina Plus contains soy lecithin

Do not take this medicine if you have a known hypersensitivity to peanuts or soy.

3. How to take Pyralgina Plus

This medicine should always be taken exactly as described in this patient leaflet or as directed by your doctor or pharmacist. In case of doubt, you should consult your doctor or pharmacist.
The dose depends on the severity of the pain and the individual's response to Pyralgina Plus.
You should always choose the smallest dose necessary to control the pain.
Adults
The recommended dose for adults is 1 or 2 tablets (400 or 800 mg of metamizole sodium, 60 or 120 mg of caffeine, and 40 or 80 mg of drotaverine hydrochloride) 2 or 3 times a day, not more often than every 6-8 hours. The maximum daily dose is 6 tablets (2,400 mg of metamizole sodium, 360 mg of caffeine, and 240 mg of drotaverine hydrochloride).
If the symptoms do not improve after 3-5 days of taking Pyralgina Plus or if the symptoms worsen despite taking the medicine, the patient should immediately consult a doctor.
Children and adolescents
Pyralgina Plus should not be taken by patients under 18 years of age (see "When not to take Pyralgina Plus" in section 2).
Elderly patients and patients in poor general health or with renal impairment (see also "When not to take Pyralgina Plus" and "Warnings and precautions" in section 2)
In elderly patients, weakened patients, and patients with impaired renal function, the dose of metamizole should be reduced due to the possibility of prolonged elimination of metamizole metabolites.
In elderly patients with poor general health and reduced creatinine clearance, a lower dose of drotaverine is recommended due to the slow metabolism of this active substance.
Patients with kidney or liver disorders (see also "When not to take Pyralgina Plus" and "Warnings and precautions" in section 2).
Due to the reduced elimination rate of metamizole in patients with kidney or liver disorders, multiple administration of high doses of metamizole should be avoided. In the case of short-term use, a dose reduction of metamizole is not required. There is a lack of experience with long-term use of metamizole.
Method of administration
Orally. The tablets should be taken with a sufficient amount of liquid (e.g., a glass of water).

Taking a higher dose of Pyralgina Plus than recommended

After taking very high doses, the elimination from the body of a harmless metabolite may cause red discoloration of the urine.
Acute overdose may cause nausea, vomiting, abdominal pain, worsening of kidney function, or acute kidney failure, and less frequently, symptoms from the central nervous system (dizziness, drowsiness, coma, convulsions), as well as a decrease in blood pressure. Patients may also experience discomfort in the chest, nervousness, irritability, tremors, muscle spasms, headache, insomnia, anxiety, euphoria, confusion, or agitation. There may also be palpitations, arrhythmias, and heart problems, which can cause fainting and cardiac arrest. Caffeine overdose may cause abdominal pain, vomiting, diuresis, tachycardia, or arrhythmias, nervous system stimulation (insomnia, anxiety, agitation, psychomotor agitation, nervousness, tremors, and convulsions).
There are no known cases of drotaverine overdose.
If you have taken more than the recommended dose of Pyralgina Plus, you should tell your doctor or pharmacist or contact the nearest hospital emergency department for further advice.

Missing a dose of Pyralgina Plus

If you miss a dose, you should take it as soon as you remember, unless it is time for the next dose. You should not take a double dose to make up for a missed dose.
If you have any further doubts about the use of this medicine, you should consult your doctor or pharmacist.

4. Possible side effects

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

Due to the risk to life, the medicine should be stopped immediately and medical help should be sought if severe allergic reactions (anaphylactic reactions) occur:

Rare side effects (less than 1 in 1,000 patients):

• facial, lip, tongue, and/or throat edema, which may cause difficulty swallowing or breathing;
• skin and mucous membrane changes, such as itching, burning, redness, rash, urticaria;

Very rare side effects (less than 1 in 10,000 patients):

• severe bronchospasm;

Side effects with unknown frequency (frequency cannot be estimated from the available data):

• anaphylactic shock (life-threatening decrease in blood pressure, weakness, fainting) (see "Warnings and precautions" in section 2).

You should stop taking Pyralgina Plus and seek medical attention immediately if you experience any of the following serious side effects:

Very rare side effects (less than 1 in 10,000 patients):

• agranulocytosis (complete or almost complete disappearance of granulocytes from the blood), including cases of death, manifested by:
• fever, chills;
• sore throat, difficulty swallowing, and inflammation of the mucous membranes of the mouth, nose, throat, genital, or anal area;
• increased sedimentation rate;
• not always normal hemoglobin, erythrocyte, and platelet values, although they are usually normal;
• slightly enlarged lymph nodes and spleen, although they are usually unchanged (see also "Warnings and precautions" in section 2);
• pancytopenia (significant reduction in the number of all blood cells: red and white blood cells and platelets), manifested by general malaise, fever, signs of infection, bruising, bleeding, pallor (see "Warnings and precautions" in section 2);
• hemolytic anemia, aplastic anemia, bone marrow damage, sometimes fatal. In patients with glucose-6-phosphate dehydrogenase deficiency, the medicine may cause hemolysis of red blood cells;
• decrease in the number of platelets (thrombocytopenia, usually manifested as increased bleeding tendency, bleeding into the skin and mucous membranes).

Side effects with unknown frequency (frequency cannot be estimated from the available data):

• severe skin reactions - red, flat spots on the torso in a target shape or round, often with blisters in the center, peeling of the skin, ulcers in the mouth, throat, nose, genitals, and eyes. The occurrence of such serious skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis); widespread rash, high body temperature, and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome);
• acute generalized exanthematous pustulosis;
• blisters (pemphigus);
• acute kidney failure, which may be accompanied by oliguria, anuria, or proteinuria;
• Kounis syndrome (acute coronary syndrome);
• liver damage;
• excessive decrease in blood pressure (occurs with unknown frequency for metamizole, rarely for drotaverine; see "Warnings and precautions" in section 2);
• analgetic asthma (see "When not to take Pyralgina Plus" in section 2), asthma attacks.

You should stop taking Pyralgina Plus and seek medical attention immediately if you experience any of the following symptoms:

Malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale 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".

Other side effects:

Uncommon (less than 1 in 100 patients):

• drug rash (transient rash of various types: papular, macular, pustular, erythematous);

Rare (less than 1 in 1,000 patients):

• skin changes with papules;
• leukopenia (decrease in the number of white blood cells in the blood);
• insomnia (associated with drotaverine);
• tremors;
• palpitations.

Frequency unknown (frequency cannot be estimated from the available data):

• gastrointestinal disorders, peptic ulcers, and bleeding, vomiting, heartburn, bloating, nausea, abdominal pain, constipation, dry mouth;
• Hepatitis, jaundice, elevated liver enzyme activity in the blood;
• headache and dizziness;
• red discoloration of the urine (after taking very high doses of metamizole);
• changes in blood glucose levels (high and low blood glucose levels);
• irritability, insomnia (associated with caffeine), nervousness, anxiety;
• psychomotor hyperactivity;
• increased cardiac contractility, irregular heart rhythm (arrhythmia), rapid heartbeat (tachycardia);
• flushing of the face, neck, and décolletage;
• rashes/eruptions of various types, exudative changes, excessive sweating;
• muscle spasms;
• fatigue;
• low blood pressure;
• withdrawal syndrome (the most common symptom of caffeine withdrawal is headache), nervousness;
• increased heart rate, increased urine flow, increased creatinine clearance, increased excretion of sodium and calcium.

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 of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store Pyralgina Plus

Do not store above 30°C. Store in the original packaging to protect from light and moisture.
The medicine should be stored out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and blister after: EXP.
The expiry date refers to the last day of the month stated.
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 Pyralgina Plus contains

• The active substances of the medicine are: metamizole sodium in the form of metamizole sodium monohydrate, caffeine, drotaverine hydrochloride.
• The other ingredients (excipients) are: microcrystalline cellulose type 112, lactose monohydrate, crospovidone, talc, magnesium stearate, coating composition: polyvinyl alcohol, titanium dioxide (E 171), talc, soy lecithin, xanthan gum.

What Pyralgina Plus looks like and contents of the pack

Coated tablets, white or almost white, oval, with the inscription "40" engraved on one side.
Blisters of OPA/Aluminum/PVC/Aluminum foil containing 6 or 12 coated tablets, in a cardboard box.

Marketing authorization holder and manufacturer

Marketing authorization holder
Zakłady Farmaceutyczne POLPHARMA S.A.
ul. Pelplińska 19, 83-200 Starogard Gdański
tel. + 48 22 364 61 01
Manufacturer
Adamed Pharma S.A.
ul. Marszałka Józefa Piłsudskiego 5
95-200 Pabianice

Date of last revision of the leaflet: