Piralgine

Package leaflet: Information for the user

PIRALGIN 500 mg/ml oral drops, solution

sodium metamizole
Generic medicine
PIRALGIN may cause an abnormally low white blood cell count (agranulocytosis), which can lead to serious and potentially fatal infections (see section 4). You must 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 you have previously had agranulocytosis while taking sodium metamizole or similar medicines, you must never take these medicines again (see section 2).
Please read all of this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See Section 4.

Contents of this leaflet:

1. What PIRALGIN is and what it is used for
2. What you need to know before taking PIRALGIN
3. How to take PIRALGIN
4. Possible side effects
5. How to store PIRALGIN
6. Contents of the pack and other information

1. What PIRALGIN is and what it is used for

PIRALGIN contains the active substance sodium metamizole, a compound with strong analgesic, antipyretic, and antispasmodic properties, used to relieve severe or resistant painful or febrile conditions.

2. What you should know before taking PIRALGIN

Do not take PIRALGIN:

• If you are allergic to metamizole or to any of the other ingredients of this medicine (listed in section 6);
• If you are allergic to other medicines belonging to the pyrazolone family (e.g. phenazone, propyphenazone) or to pyrazolidines (e.g. phenylbutazone, oxyphenbutazone);
• If you have previously experienced a significant reduction in a type of white blood cells called granulocytes, caused by metamizole or other medicines known as pyrazolones or pyrazolidines;
• If you have bone marrow problems or a disease affecting the production or function of blood cells;
• If you have previously experienced bronchospasm (a contraction of the bronchi that may lead to breathing difficulties) or other allergic reactions (e.g. urticaria, rhinitis, angioedema – swelling of the throat, face, or limbs) after using analgesics such as salicylates, paracetamol, diclofenac, ibuprofen, indomethacin, naproxen;
• If you suffer from a condition called "acute intermittent hepatic porphyria", because PIRALGIN may trigger an attack of this disease;
• If you suffer from a condition called favism, caused by a congenital deficiency of an enzyme called glucose-6-phosphate dehydrogenase, because PIRALGIN may cause destruction of red blood cells, with risk of hemolysis;
• If you are in the last three months of pregnancy;
• If you have fertility issues or are undergoing fertility investigations;

Warnings and precautions:
Talk to your doctor or pharmacist before taking PIRALGIN.

Unusually low white blood cell count (agranulocytosis)
PIRALGIN may cause agranulocytosis, a very low level of a type of white blood cells called granulocytes, which are important for fighting infections (see section 4). You must stop taking metamizole and consult a doctor immediately if you experience any of the following symptoms, as they may indicate possible agranulocytosis: chills, fever, sore throat, and painful ulcers on mucous membranes (moist linings of body cavities), especially in the mouth, nose, throat, genital or anal areas.
Your doctor will perform a laboratory test to check your blood cell levels.
If you are taking metamizole for fever, some symptoms of newly developed agranulocytosis may go unnoticed. Similarly, symptoms may also be masked if you are undergoing antibiotic therapy.
Agranulocytosis may develop at any time during PIRALGIN use and even shortly after stopping metamizole.
You may develop agranulocytosis even if you have previously used metamizole without problems.
Metamizole may cause a serious blood cell disorder called "pancytopenia".
Stop treatment immediately and contact your doctor immediately if you experience any of the following symptoms:

• General malaise,
• Infections,
• Persistent fever,
• Reddish-purple spots on the skin (bruising, ecchymoses),
• Bleeding,
• Pallor.

Metamizole may cause a serious disorder of certain blood cells called "thrombocytopenia".
Stop treatment and consult your doctor immediately if you experience bleeding (hemorrhage), with or without small reddish-purple spots on the skin (petechiae).

Allergic (anaphylactic/anaphylactoid) reactions and anaphylactic shock
Stop treatment with PIRALGIN immediately and consult your doctor if you experience any of the following symptoms:

• Swelling of the throat (larynx), face, or limbs (angioedema),
• Skin problems with redness and possible itching (urticaria, rash),
• Breathing difficulties (dyspnea),
• Pallor,
• Increased blood flow in certain areas of the body (generalized hyperemia),
• General malaise,
• Low blood pressure (hypotension),
• Shock.

These reactions occur mainly in sensitive patients; therefore, PIRALGIN should be used with caution if you have:

• Analgesic-induced asthma or intolerance to any type of analgesic drug associated with urticaria and angioedema (facial, limb, or throat swelling) (see "Do not take PIRALGIN if"),
• Frequent allergic reactions (atopic patient),
• Bronchial asthma, especially if associated with nasal polyps and frequent colds (polyposis rhinosinusitis),
• Frequent (chronic) urticaria,
• Alcohol intolerance, i.e. reacting to even small amounts of alcohol with sneezing, tearing, or facial flushing,
• Allergy (intolerance) to dyes (e.g. tartrazine) or preservatives (e.g. benzoates).

If you suffer from any of these conditions, discuss them with your doctor before taking PIRALGIN.
In such cases, if you have previously experienced an allergic (hypersensitivity) reaction to metamizole, you must never take metamizole or other pyrazolone-containing medicines again.

Severe skin reactions
Severe skin reactions, including Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported in association with metamizole treatment. Discontinue use of metamizole and seek immediate medical attention if you experience any symptoms related to these severe skin reactions described in section 4.
If you have previously developed severe skin reactions, you must not restart treatment with PIRALGIN at any time (see section 4).
Stop treatment and do not restart if you develop progressive skin and mucous membrane disorders, often with redness, blisters, and bullae, as these could be symptoms of such serious conditions.

Isolated hypotensive reactions
Administration of metamizole may increase the risk of severe drop in blood pressure (see section 4).
These reactions are dose-dependent and are more likely with injectable administration.
Furthermore, the risk of severe hypotensive reactions is increased:

• If intravenous administration is not performed slowly;
• If you already have low blood pressure, dehydration, or circulatory instability or disorder (incipient circulatory failure);
• If you have high fever;
• If you have vascular disorders affecting the heart (severe coronary insufficiency) or narrowing (stenosis) of vessels supplying the brain and are taking PIRALGIN; your doctor will periodically perform certain tests (hemodynamic monitoring) to prevent a drop in blood pressure, which would be harmful in these cases.

Avoid using PIRALGIN for minor conditions and use the medicine only for the shortest duration necessary to control pain and fever. The use of analgesic medicines at high doses or for prolonged periods should be evaluated by a doctor.

Liver problems
Liver inflammation with symptoms appearing within a few days or months after starting treatment has been reported in patients taking metamizole.
Stop using PIRALGIN and contact a doctor if you experience symptoms of liver problems such as malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale stools, yellowing of the skin or whites of the eyes (jaundice), itching, skin rash, or upper abdominal pain. Your doctor will check liver function.
You must not take PIRALGIN if you have previously taken a medicine containing metamizole and experienced liver problems.

Other medicines and PIRALGIN
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription.
Metamizole may affect the action of other medicines, and conversely, these may affect the action of metamizole. Therefore, it is important to inform your doctor if you are taking:

• Medicines that suppress the immune system and are used to prevent organ transplant rejection (e.g. cyclosporine);
• Acetylsalicylic acid: metamizole (the substance used to reduce pain and fever) may reduce the effect of acetylsalicylic acid on platelet aggregation (blood cells that clump together to form a clot) when taken concurrently. Therefore, this combination should be used cautiously in patients taking low-dose aspirin for cardioprotection;
• Methotrexate (used for cancer and autoimmune diseases), because metamizole may increase methotrexate toxicity, especially in elderly patients. Avoid combining PIRALGIN with methotrexate;
• Bupropion, a medicine used to treat depression or as an aid to quit smoking;
• 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 transplant patients;
• Sertraline, a medicine used to treat depression.

In patients treated with metamizole, interference has been reported with laboratory tests using the Tinder method or a method similar to Tinder, for example tests measuring blood levels of creatinine, triglycerides, HDL cholesterol, and uric acid.

PIRALGIN with food, drinks, and alcohol
Do not consume alcohol during treatment with PIRALGIN.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning a pregnancy, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Pregnancy
Available data on the use of metamizole during the first three months of pregnancy are limited but do not indicate harmful effects on the embryo. In selected cases, when no other treatment options are available, single doses of metamizole during the first and second trimesters may be acceptable after consulting your doctor and carefully weighing the benefits and risks of metamizole. However, in general, the use of metamizole is not recommended during the first and second trimesters.
You must not use PIRALGIN during the last three months of pregnancy due to an increased risk of possible complications for both mother and baby (bleeding, premature closure of an important fetal vessel, the so-called ductus arteriosus, which normally closes only after birth).

Breastfeeding
Metamizole metabolites pass into breast milk in considerable amounts, and the risk to breastfed infants cannot be excluded. In particular, repeated use of metamizole during breastfeeding should be avoided. After a single dose of metamizole, mothers are advised to collect and discard breast milk for 48 hours following administration.

Fertility
Do not take PIRALGIN if you are planning a pregnancy, have difficulty conceiving, or are undergoing fertility tests.

Driving and using machines
At higher doses, the ability to concentrate and react may be impaired, increasing the risks associated with driving vehicles or operating machinery, especially if alcohol has been consumed (see also PIRALGIN with food, drinks, and alcohol).

PIRALGIN contains sodium
PIRALGIN oral drops contain 1.5 mmol (34.6 mg) of sodium per ml (20 drops). This corresponds to 1.8% of the maximum daily recommended dietary intake of sodium for an adult.

3. How to take PIRALGIN

Take this medicine exactly as directed by your doctor. If you have any doubts, consult your
doctor or pharmacist.
500 mg/ml oral drops, solution (1 ml = 20 drops).
The dose depends on the intensity of pain or fever and on individual sensitivity to PIRALGIN. The lowest effective dose required to control pain and fever should always be used. Your doctor will tell you how to take PIRALGIN.
The following table shows the recommended single doses and maximum daily doses according to body weight or age:

Single doses may be administered up to four times daily, depending on the maximum daily dose.
A noticeable effect is expected 30 to 60 minutes after oral administration.
Use in Children and Adolescents
Give this medicine to your child exactly as directed by the doctor. If you have any doubts, consult your doctor or pharmacist.
For the treatment of pain, children and adolescents up to 14 years of age may take a single dose of 8 to 16 mg of PIRALGIN per kilogram of body weight (see the following table). For fever, a dose of 10 mg of PIRALGIN per kilogram of body weight is generally sufficient in children:

Use PIRALGIN only for short-term treatment and in cases of severe symptoms.
Your doctor will assess the need for longer-term treatment.

Elderly patients and patients in poor general health/with reduced renal function
Dosage reduction is necessary in elderly patients, debilitated patients, and patients with reduced renal function, as there may be delayed excretion of metabolites derived from metamizole metabolism.

Patients with impaired renal or hepatic function
High repeated doses should be avoided in patients with impaired renal or hepatic function due to reduced elimination rate. For short-term use only, no dosage reduction is required. There is no experience regarding long-term use.

If you take more PIRALGIN than you should
If you take an excessive dose of PIRALGIN, inform your doctor immediately or go to the nearest hospital.
If you take more metamizole than you should, your blood pressure may suddenly drop and you may experience:

• nausea,
• vomiting,
• diarrhea,
• kidney problems (acute renal failure). Less commonly, you may have:
• central nervous system symptoms:
  • dizziness,
  • drowsiness,
  • coma,
  • convulsions,
• drop in blood pressure sometimes leading to shock,
• increased heart rate (tachycardia),
• red discoloration of the urine.

If you forget to take PIRALGIN
Do not take a double dose to make up for the missed dose. Simply take the next dose as scheduled.
If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, PIRALGIN may cause side effects, although not everyone will experience them.
Stop using PIRALGIN and contact a doctor immediately if you experience any of the following symptoms:

• feeling unwell (nausea or vomiting), fever, feeling tired, loss of appetite, dark-coloured urine, pale-coloured stools, yellowing of the skin or the whites of the eyes, itching, skin rash or pain in the upper part of the stomach. These symptoms may be signs of liver damage. See also section 2 Warnings and precautions.
• severe allergic reaction with sudden onset
• severe and widespread skin rashes
• severe and sudden swelling of the skin or mucous membranes (e.g. swelling around the eyes, face, lips, mouth or throat)
• severe difficulty breathing, irregular heartbeat
• severe and sudden drop in blood pressure
• circulatory shock
• severe blistering skin lesions characterized by areas of skin detachment particularly around the mouth, nose, eyes and genitals, and frequent skin rashes with inflammation (Stevens-Johnson syndrome and Lyell's syndrome)
• persistent and recurring fever, chills, sore throat, mucosal lesions (lesions in the oral cavity, genitals, anorectal area); these symptoms could indicate a condition known as

agranulocytosis (reduction in a type of white blood cells)
Other side effects associated with the use of PIRALGIN are:
Uncommon side effects (may affect from 1 to 10 people in 1,000):

• allergic reactions (anaphylactic/anaphylactoid), with skin and mucous membrane disorders (such as itching, burning, redness, hives, swelling)
• difficulty breathing
• stomach and intestinal disorders (less frequently)

In more severe cases the following may occur:

• generalized hives,
• swelling of the throat (larynx), face and limbs (severe angioedema),
• severe constriction of the bronchi with difficulty breathing (bronchospasm),
• changes in heart rhythm,
• drop in blood pressure (sometimes preceded by a rise in blood pressure),
• allergic shock (anaphylactic).

These reactions may occur immediately after administration of PIRALGIN or even hours later; however, they usually occur within the first hour after administration.
If you suffer from asthma caused by pain medicines (analgesics), intolerance reactions typically manifest as asthma attacks.

• drop in blood pressure which may be occasional or transient, or rarely may present as an acute drop in blood pressure.

Rare side effects (may affect from 1 to 10 people in 10,000)

• skin disorders called fixed drug eruptions,
• redness (rash)

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

• inflammation of the liver, yellowing of the skin and the whites of the eyes, increased liver enzymes in the blood.
• acute allergic heart disease (Kounis syndrome).
• skin diseases such as “Stevens-Johnson syndrome” or “Lyell's syndrome”, which can be life-threatening. If you develop these skin lesions, stop taking the medicine immediately and consult your doctor.
• anaemia (aplastic anaemia).
• changes in the number of certain blood cells (agranulocytosis, pancytopenia, which may be fatal, leucopenia and thrombocytopenia). See “Warnings and precautions”. Typical symptoms of agranulocytosis (characterized by a reduced number of certain blood cells called granulocytes) are:
  • inflammatory lesions of the mucous membranes (e.g. mouth and throat, anorectal, genital),
  • sore throat,
  • fever (including persistent or recurring fever). Typical symptoms of “thrombocytopenia” include:
  • increased tendency to bleed,
  • red spots on the skin or mucous membranes (petechiae).
• worsening of kidney function (acute renal failure), which in some cases may be accompanied by:
  • reduced urine output (oliguria),
  • absence of urine output (anuria),
  • presence of protein in the urine (proteinuria),
• severe kidney disease called “acute interstitial nephritis”,
  • red discolouration of the urine, which disappears at the end of treatment.
  • gastrointestinal bleeding.

Severe skin reactions
Stop treatment with metamizole and contact your doctor immediately if you experience any of the following severe side effects:

• flat, reddish patches on the trunk, target-shaped or circular, often with central blisters, skin peeling, mouth, throat, nose, genital and eye ulcers. These severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis);
• widespread skin rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

These reactions can occur even if you have previously used PIRALGIN without complications.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store PIRALGIN

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after 'Exp'.
The expiry date refers to the last day of that month.
The shelf life after first opening the bottle is 2 years.
Do not store above 25 °C.
Keep PIRALGIN in the original packaging to protect the medicine from light.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What PIRALGIN contains
The active substance is metamizole sodium.
1 ml of solution (equivalent to 20 drops) contains 500 mg of metamizole.
The other components are: trisodium phosphate dodecahydrate, monosodium phosphate dihydrate, strawberry flavour, purified water.

Description of the appearance of PIRALGIN and contents of the pack
Oral drops, solution.
20 ml coloured glass bottle with dropper and cap equipped with a “child-resistant closure”.
To open, press down on the cap while simultaneously unscrewing it counterclockwise. Close after use. The bottle is properly closed if, when unscrewing the cap without pressing, a click is heard.

Marketing Authorisation Holder and Manufacturer:
Marketing Authorisation Holder
So.Se.PHARM S.r.l.
Via dei Castelli Romani, 22
00071 Pomezia
Italy

Manufacturer
Special Product’s Line S.p.A.
Via Fratta Rotonda Vado Largo, 1
03012 Anagni (FR)
Italy