Domilgan

Package leaflet: Information for the patient

Domilgan, 1000 mg, effervescent powder for oral solution in a sachet
Metamizolum natricum monohydricum
Domilgan may cause a significantly low number of white blood cells (agranulocytosis), which can
lead to severe and life-threatening infections (see section 4).
Treatment should be discontinued and immediate medical advice sought if any of the following
symptoms occur: fever, chills, sore throat, painful ulcers in the nose, mouth, throat, or in the genital
or anal area.
If the patient has ever experienced agranulocytosis during treatment with metamizole or similar
medicinal products, this medicine must never be taken again in the future (see section 2).
Please read this leaflet carefully before taking the medicine, as it contains important information
for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents

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

1. What Domilgan is and what it is used for

The active substance in Domilgan is metamizole, a pyrazolone derivative with analgesic and
antipyretic properties.
Even at high doses, metamizole does not affect intestinal peristalsis and does not cause constipation.
Domilgan is indicated for short-term treatment of severe pain of various origins and for fever when
other medicines are contraindicated or ineffective, in:

• headaches,
• migraine,
• toothache,
• muscle and joint pain,
• traumatic and postoperative pain,
• pain caused by renal colic,
• biliary colic,
• pain in neoplastic diseases,
• fever.

2. Important information before taking Domilgan
When not to take Domilgan

• if the patient has previously experienced a significant decrease in the number of white blood cells with a lack of granulocytes caused by metamizole or other similar medicines called pyrazolones or pyrazolidines,
• if the patient has bone marrow dysfunction or a disease affecting blood cell production or function,
• if the patient is allergic to metamizole and other pyrazolone and pyrazolidine derivatives, e.g., propyphenazone, phenazone or phenylbutazone (medicines with antipyretic, analgesic and anti-inflammatory effects), especially if agranulocytosis (an acute condition associated with a severe, life-threatening decrease in the number of granulocytes in the blood) occurred after taking any of these medicines, or to any of the other components of this medicine (listed in section 6),
• if the patient has analgesic-induced asthma syndrome or intolerance to painkillers, manifested by urticaria, angioedema, i.e., when the patient reacts with bronchospasm or another anaphylactoid reaction (similar to an allergic reaction) to salicylates, paracetamol or other non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs), such as: diclofenac, ibuprofen, indomethacin or naproxen, allergy to non-steroidal anti-inflammatory drugs,
• severe kidney and liver diseases,
• acute hepatic porphyria,
• after cytostatic treatment (medicines used in cancer chemotherapy),
• if blood morphology shows abnormalities (agranulocytosis, leukopenia),
• if the patient has anaemia,
• if the patient has congenital glucose-6-phosphate dehydrogenase deficiency,
• with other medicines from the group of pyrazolone derivatives (aminophenazone, phenylbutazone, oxyphenbutazone),
• in children and adolescents under 15 years of age,
• if the patient is in the last three months of pregnancy.

Warnings and precautions
Before starting Domilgan, discuss with your doctor, pharmacist or nurse if the patient has:

• systolic blood pressure below 100 mm Hg or heart and circulatory disorders (e.g., myocardial infarction, coronary heart disease or multi-organ trauma), cerebral vessel stenosis, reduced circulating blood volume, dehydration, high fever, as the medicine may cause a drop in blood pressure,
• kidney and/or liver failure,
• peptic ulcer disease of the stomach and duodenum,
• bronchial asthma or analgesic-induced asthma or intolerance to painkillers manifested by urticaria, swelling of the tongue, face, lips, and/or throat, especially if associated with nasal polyps and chronic inflammation of the nasal and sinus mucosa,
• allergic diseases, including atopic conditions, chronic urticaria,
• intolerance to certain dyes (e.g., tartrazine) or preservatives (e.g., benzoates),
• alcohol intolerance manifested by sneezing, tearing, and severe facial flushing even after small amounts of alcohol; this may indicate previously undiagnosed analgesic-induced asthma.

Abnormally low number of white blood cells (agranulocytosis)
Domilgan may cause agranulocytosis, i.e., 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). Treatment with metamizole should be discontinued and immediate medical advice sought if the following symptoms occur, as they may indicate possible agranulocytosis: chills, fever, sore throat, and painful mucosal ulcers, especially in the oral cavity, nose, throat, or in the genital or anal area.
The doctor will order laboratory tests to check the patient's 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 receiving antibiotics.
Agranulocytosis may develop at any time during treatment with Domilgan, and even shortly after discontinuation of metamizole.
Agranulocytosis may occur even if metamizole was previously administered without complications.

Liver-related disorders
Cases of hepatitis have been reported in patients taking metamizole, with symptoms appearing from several days to several months after starting treatment.
The use of Domilgan should be discontinued and medical advice sought if the patient experiences liver-related symptoms such as: malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale stools, jaundice (yellowing of the skin or whites of the eyes), itching, rash, or upper abdominal pain. The doctor will monitor liver function in the patient.
The patient should not take Domilgan if previously treated with any medicinal products containing metamizole and experienced liver-related disorders.

Immediate discontinuation of the medicine and seeking medical help is required if symptoms of an allergic (anaphylactic) reaction occur, e.g.:

• swelling of the face, lips, tongue and/or throat, which may cause difficulty in swallowing or breathing,
• severe bronchospasm,
• skin and mucosal changes such as itching, burning, redness, urticaria,
• shock (a life-threatening reaction due to allergic reaction, causing disturbances in the body's autoregulatory mechanisms, unable to ensure adequate blood flow to vital organs and tissues, manifested by confusion, weakness, and fainting). Patients at increased risk of severe reactions similar to anaphylactoid reactions should only receive metamizole under strict medical supervision, with immediate access to emergency treatment. Patients who have experienced an allergic or other immunological reaction to metamizole are also at risk of a similar reaction to other pyrazolones, pyrazolidines, and other non-opioid analgesics. Anaphylactic shock may occur in patients with allergies. Therefore, particular caution is advised in patients with asthma or atopy (e.g., atopic dermatitis or mucosal inflammation, hay fever, allergic asthma).

The medicine should be discontinued immediately and medical advice sought if the patient experiences:

• agranulocytosis manifested by, for example, elevated body temperature accompanied by chills, sore throat, difficulty swallowing, and ulcers in the oral cavity, nose, throat, genital organs, or rectum. Patients who have experienced agranulocytosis in response to sodium metamizole monohydrate are particularly at risk of a similar reaction to other pyrazolones and pyrazolidines;
• thrombocytopenia (reduced platelet count causing blood clotting disorders), e.g.: petechiae on the skin and mucous membranes, bruises, recurrent bleeding from gums, nose, gastrointestinal tract;
• pancytopenia (significant reduction in all blood cells: red and white blood cells and platelets), e.g.: general malaise, fever, frequent infections, bruises, bleeding, pallor.

If any of the above symptoms occur, metamizole must never be used again!
If metamizole administration is necessary, the doctor must perform regular blood tests, as metamizole may cause bone marrow damage.
Blood morphology should be monitored in oncology patients receiving metamizole.

Severe skin reactions
Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported with metamizole treatment. If any of these symptoms associated with severe skin reactions listed in section 4 occur, treatment with metamizole should be discontinued and immediate medical help sought.
If the patient has ever experienced severe skin reactions, Domilgan treatment must never be resumed in the future (see section 4).

Children and adolescents
Domilgan is contraindicated in children and adolescents under 15 years of age due to the fixed content of 1000 mg of metamizole per sachet. Other pharmaceutical forms or strengths of metamizole-containing medicines are available, which can be appropriately dosed for younger children.

Domilgan with other medicines
Inform your doctor about all medicines currently or recently taken, as well as any medicines the patient plans to take.
Concomitant use of Domilgan with pyrazolone and pyrazolidine derivatives (aminophenazone, phenylbutazone, oxyphenbutazone) is contraindicated. These are medicines with analgesic, antipyretic and anti-inflammatory effects.
Before using this medicine, consult your doctor if the patient is taking:

• anticoagulants, coumarin derivatives,
• oral antidiabetic medicines,
• phenytoin (an antiepileptic medicine),
• sulfonamides (antibacterial medicines),
• antidepressants,
• oral contraceptives and allopurinol, as they may slow down the metabolism of monohydrated sodium metamizole and increase its toxicity,
• cyclosporine (an immunosuppressive medicine used, among others, to prevent transplant rejection). Monohydrated sodium metamizole may reduce cyclosporine serum concentration. When both medicines are used concomitantly, dose adjustment of monohydrated sodium metamizole should be considered.
• barbiturates (e.g., phenobarbital – a medicine used, among others, in epilepsy). Barbiturates reduce the effect of monohydrated sodium metamizole.
• monoamine oxidase inhibitors - MAO inhibitors (e.g., selegiline, moclobemide – medicines used, among others, in depression). MAO inhibitors enhance the effect of metamizole.
• chlorpromazine (a medicine used, among others, in the treatment of schizophrenia). Concomitant use of monohydrated sodium metamizole and chlorpromazine may cause severe hypothermia.
• monohydrated sodium metamizole may enhance the haematotoxicity of methotrexate, especially in elderly patients. Concomitant use of both medicines should be avoided.
• with pyrazolone derivatives, including monohydrated sodium metamizole, interactions may occur with captopril, lithium, and triamterene. These medicines may alter the efficacy of antihypertensive and diuretic medicines. There is no information whether monohydrated sodium metamizole also causes such interactions;
• bupropion, a medicine used in the treatment of depression or as an aid in smoking cessation,
• efavirenz, a medicine used in the treatment of HIV infection (AIDS),
• methadone, a medicine used in the treatment of addiction to illegal narcotics (so-called opioids),
• valproate, a medicine used in the treatment of epilepsy or bipolar affective disorder,
• tacrolimus, a medicine used to prevent organ rejection in transplant patients,
• sertraline, a medicine used in the treatment of depression.

Metamizole may reduce the effect of acetylsalicylic acid on platelets. Caution is advised when acetylsalicylic acid is used concomitantly for the prevention of heart disease.

Domilgan with food, drink or alcohol
The medicine should be taken during or immediately after meals.
Alcohol may affect the efficacy of the medicine.

Pregnancy and breastfeeding and effect on fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using 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, if no other treatment options are available, after consultation with a doctor or pharmacist, the patient may take single doses of metamizole during the first and second trimesters, provided the benefits and risks of taking the medicine are carefully considered. In principle, administration of metamizole during the first and second trimesters is not recommended.
Domilgan must not be taken during the last three months of pregnancy due to the increased risk of complications for mother and child (bleeding, premature closure of an important vessel, the so-called ductus arteriosus Botalli, in the unborn child, which normally closes only after birth).

Breastfeeding
Metamizole metabolites pass into breast milk in significant amounts, and a risk to the breastfed infant cannot be excluded. Therefore, repeated use of metamizole during breastfeeding should be particularly avoided.
After a single dose of metamizole, mothers should be advised to express and discard milk for 48 hours after administration of the medicine.

Driving and operating machinery
At the recommended dosage range, no impairment of concentration or reaction ability has been observed. However, as a precaution, especially when higher doses are used, the possibility of impaired abilities should be considered, and operation of machinery, driving vehicles, or performing risky activities should be avoided.

Domilgan contains sodium
One sachet of the medicine contains 82.7 mg of sodium (the main component of table salt). This corresponds to 4.14% of the maximum recommended daily sodium intake in the diet of adults.

Domilgan contains glucose
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking the medicine.

Domilgan contains 3.27 g of mannitol (E421) per sachet
The medicine may have a mild laxative effect.

3. How to take Domilgan
This medicine should always be taken according to the instructions given by the doctor or pharmacist. If in doubt, consult your doctor or pharmacist.
The dose depends on the severity of pain or fever and the individual's response to Domilgan. The lowest effective dose required to control pain and fever should always be used. The treating doctor will advise the patient on how to take Domilgan.

Adults and adolescents aged 15 years or older (with body weight exceeding 53 kg) may take 1 sachet as a single dose, no more than four times daily at intervals of 6-8 hours. The maximum daily dose for adults and adolescents aged over 15 years is 4 sachets of the effervescent powder for oral solution (equivalent to 4000 mg of metamizole).
Domilgan should not be used in adolescents under 15 years of age or in children, as in such cases, pharmaceutical forms containing a lower amount of active substance are required (see also "When not to take Domilgan").

Method of administration:
The medicine should be taken during or immediately after meals. The contents of the sachet should be dissolved in a glass of water and taken immediately after dissolution, within no more than 5 minutes.
The dissolved medicine, if not consumed within 5 minutes, should be discarded.

Elderly patients and patients in poor general health or with kidney impairment
In elderly patients, weakened patients, and patients with impaired kidney function, the dose should be reduced due to the possibility of prolonged elimination of metamizole metabolites.

Patients with impaired kidney or liver function
Due to reduced elimination rate in patients with impaired kidney or liver function, repeated administration of high doses should be avoided. In case of short-term use, dose reduction is not required. There is no experience with long-term use.

Use in children and adolescents
Domilgan should not be used in children and adolescents under 15 years of age (see also "When not to take Domilgan").

Taking more than the recommended dose of Domilgan
If more than the recommended dose is taken, seek immediate medical advice from a doctor or pharmacist.

Symptoms of overdose:
Dizziness, tinnitus, hearing disturbances, psychomotor agitation, disturbances of consciousness, coma, convulsions, decreased blood pressure, cardiac arrhythmias (tachycardia) may occur. Overdose of monohydrated sodium metamizole may also cause abdominal pain, vomiting, gastric and duodenal mucosal erosions, bleeding, perforation (rupture of the wall of an internal organ), liver cell damage, interstitial nephritis, necrosis of renal tubules, and bronchospasm.
Cases of rash, urticaria, angioedema, exfoliative dermatitis, and toxic epidermal necrolysis (Lyell's syndrome) have been reported. After ingestion of very high doses, excretion of rubazonic acid may cause red discoloration of urine.
There is also a possibility of blood and haematopoietic system disorders, e.g., leukopenia (reduced number of white blood cells), thrombocytopenia (reduced number of platelets), bone marrow damage, anaemia due to impaired haematopoietic function of the bone marrow.
There is no specific antidote for monohydrated sodium metamizole.
In case of overdose, immediate medical attention is required. Symptomatic and supportive treatment may be necessary.

Missed dose of Domilgan
Do not take a double dose to make up for a missed dose.
If you have any further doubts regarding the use of this medicine, consult your doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You must stop taking Domilgan and seek immediate medical help if any of the following symptoms occur:
General malaise (nausea or vomiting), fever, feeling of 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".

Due to life-threatening risk, the medicine must be discontinued immediately and medical help must be sought if severe allergic (anaphylactic) reactions occur:

Rare (may occur in fewer than 1 in 1,000 patients):

• swelling of the face, lips, tongue and/or throat, breathing difficulties, which may cause difficulty swallowing and breathing.
• asthma attack, bronchospasm, shortness of breath.

Very rare (may occur in fewer than 1 in 10,000 patients):

• severe bronchospasm,
• skin and mucous membrane changes such as itching, burning, redness, urticaria.

Frequency not known:

• anaphylactic shock (life-threatening drop in blood pressure, weakness, fainting).

Immediately discontinue the medicine and consult a doctor if any of the following adverse reactions occur:

Uncommon (occurring in fewer than 1 in 100 patients):

• drug rash,
• excessive decrease in blood pressure.

Rare (occurring in fewer than 1 in 1,000 patients):

• rash (e.g. maculopapular),
• seizure-like convulsions after high doses of the medicine.

Very rare:

• erythema multiforme bullosum (Stevens-Johnson syndrome, blistering due to erosion on mucous membranes of the oral cavity, conjunctiva, genital organs),
• toxic epidermal necrolysis (Lyell's syndrome), erythematous-bullous skin and mucous membrane lesions leading to peeling of large skin areas, exposure of extensive skin surfaces,
• thrombocytopenia (bruising, bleeding),
• pancytopenia,
• agranulocytosis manifested by: high fever, chills, sore throat, difficulty swallowing, and inflammatory conditions of the mucous membranes of the mouth, nose, throat, genital organs and rectum, including cases resulting in death,
• analgesic-induced asthma (see section 2 "When not to take Domilgan"),
• sudden deterioration in kidney function with proteinuria, oliguria or anuria, including acute kidney failure,
• interstitial nephritis.

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

• liver damage, cholestasis (mechanical obstruction of bile outflow), hepatitis, jaundice (yellowing of the skin and whites of the eyes), increased liver enzyme activity in blood,
• haemolytic anaemia (anaemia caused by accelerated breakdown of red blood cells), haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency; aplastic anaemia, bone marrow damage, sometimes resulting in death,
• rapid heartbeat, cyanosis,
• severe skin reactions: treatment with metamizole must be discontinued and immediate medical help sought if any of the following serious adverse reactions occur:
• red, flat spots on the trunk in the shape of a target or circular, often with blisters in the center, skin peeling, ulcers in the mouth, throat, nose, genital organs and eyes. 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).

Other adverse reactions
Consult a doctor if any of the following adverse reactions occur:

Rare (occurring in fewer than 1 in 1,000 patients):

• leukopenia (reduced number of white blood cells in blood),
• purpura.

Very rare (occurring in fewer than 1 in 10,000 patients):

• increased bilirubin concentration in blood.

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

• nausea, vomiting, abdominal pain, gastric irritation, diarrhoea, dry mouth,
• headache, dizziness,
• decreased appetite,
• red discoloration of urine (after administration of very high doses of metamizole).

Reporting of adverse reactions
If any adverse reactions occur, including those not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C
02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Domilgan

No special temperature storage requirements for this medicinal product.
Keep in the original packaging to protect from light and moisture.
Keep the medicine out of sight and reach of children.
Do not use this medicine if you notice any changes in the appearance of the powder.
Do not use this medicine after the expiry date stated on the sachet and outer carton following the abbreviation "EXP". The expiry date refers to the last day of the specified month.
The abbreviation "Lot" on the packaging refers to the batch number.
Medicines must not be disposed of via the sewage system or household waste. Ask your pharmacist how to dispose of medicines no longer in use. This will help protect the environment.

6. Contents of the pack and other information

What Domilgan contains
Active substance: metamizole sodium monohydrate.
Each sachet contains 1000 mg of metamizole sodium monohydrate.
Other components: mannitol (E421), sodium cyclamate, strawberry flavour, colloidal anhydrous silica.
Composition of strawberry flavour: cis-3-hexen-1-ol, 4-hydroxy-2,5-dimethyl-3-furanone, maltol, methyl cinnamate, ethyl 2-methylbutyrate, ethyl caproate, 2-methylbutyric acid, ethyl butyrate, hex-2(trans)-enol, gamma decalactone, caproic acid nat, anhydrous corn glucose syrup, gum arabic (E414), silicon dioxide (E551).

What Domilgan looks like and contents of the pack
Domilgan 1000 mg is a white or almost white powder with a strawberry flavour, packed in 4.5 g sachets made of Polyethylene/Aluminium/Paper foil.
The pack contains 6 sachets or 20 sachets and a patient leaflet, in a cardboard box.

Marketing Authorisation Holder
SOLINEA Sp. z o.o.
Elizówka, Szafranowa 6 Street
21-003 Ciecierzyn
Poland
Tel: 81463-48-82

Manufacturer
CHEMAX PHARMA LTD
8A Goritsa str., 1618 Sofia
Bulgaria

Other sources of information
Detailed information about this medicinal product is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, www.urpl.gov.pl