Domilgan

Domilgan may cause an abnormally low number of white blood cells (agranulocytosis), which can lead to severe and life-threatening infections (see section 4).
Treatment should be discontinued and medical advice should be sought immediately if any of the following symptoms occur: fever, chills, sore throat, painful ulcers in the nose, mouth, throat, genital area or around the anus.
If the patient has ever experienced agranulocytosis during treatment with metamizole or similar medicines, this medicine must never be taken again in the future (see section 2).
Package leaflet: Information for the patient
Domilgan, 500 mg/mL, oral drops, solution
Metamizolum natricum monohydricum
Please read carefully all the information in this leaflet before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet so that you can read it again if necessary.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If any adverse reactions occur in the patient, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

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

Domilgan contains metamizole sodium monohydrate and is an analgesic and antipyretic medicine belonging to a group of drugs called pyrazolones. Domilgan is used in:

• acute, severe pain following injuries or surgery,
• colicky abdominal pain (colic),
• pain in malignant diseases,
• other acute and prolonged severe pain when other treatment methods are contraindicated,
• high temperature (fever) unresponsive to other treatments.

2. Important information before using Domilgan

When not to use Domilgan:

• If the patient has previously experienced a significant decrease in the number of white blood cells called granulocytes, caused by metamizole or other similar drugs known as pyrazolones or pyrazolidines,
• if the patient has impaired bone marrow function or a condition affecting the production or function of blood cells,
• if the patient is allergic to metamizole or other pyrazolones (e.g. phenazone, propyphenazone) or pyrazolidines (e.g. phenylbutazone, oxyphenbutazone),
• if the patient is allergic to any of the other ingredients of the medicine (listed in section 6),
• if the patient has known intolerance to painkillers (analgesic asthma syndrome or intolerance to painkillers manifesting as urticaria and/or angioedema). This applies to patients who, after exposure to painkillers such as salicylates, paracetamol, diclofenac, ibuprofen, indomethacin or naproxen, experience bronchospasm (sudden narrowing of the lower airways) or other symptoms of hypersensitivity reactions, such as itching, rhinitis and angioedema (urticaria, rhinitis, angioedema),
• if the patient has ever experienced an allergic reaction such as a severe skin reaction to this medicine (see also section 4 below),
• if the patient has impaired bone marrow function following anticancer therapy,
• if the patient has a congenital disorder associated with a risk of red blood cell breakdown (genetically determined glucose-6-phosphate dehydrogenase deficiency),
• if the patient has porphyria (a rare inherited disorder associated with impaired red blood cell formation),
• if the patient has acute renal or hepatic failure, or acute hepatic porphyria (a hereditary disorder associated with impaired haemoglobin synthesis),
• if the patient is in the last three months of pregnancy.

Warnings and precautions
Before starting treatment with Domilgan, discuss this with your doctor.
Domilgan contains metamizole, which is associated with a rare but life-threatening risk of:

• sudden circulatory arrest,
• agranulocytosis (acute disorder caused by a significant decrease in the number of certain white blood cells).

Low white blood cell count (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 must be discontinued and medical advice sought immediately if any of the following symptoms occur, as they may indicate possible agranulocytosis: chills, fever, sore throat and painful ulceration of the mucous membranes, especially in the oral cavity, nose and 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 used for fever, some symptoms of developing agranulocytopenia 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.
If the patient develops symptoms indicating a reduced number of all blood cells (pancytopenia), e.g. general malaise, infection, persistent fever, bruising, bleeding, pallor, or reduced platelet count (thrombocytopenia), e.g. increased tendency to bleed, small bleedings within the skin and mucous membranes, treatment with Domilgan drops must be immediately discontinued and medical advice sought as soon as possible from a doctor (see section 4 "Possible side effects").
If the patient experiences an allergic-type reaction to Domilgan drops, he or she is also particularly at risk of a similar reaction to other painkillers.
If the patient experiences an allergic reaction or other immunological reaction (e.g. agranulocytosis) to Domilgan drops, he or she is also particularly at risk of a similar reaction to other pyrazolones and pyrazolidines (similar chemical substances), such as phenazone, propyphenazone, phenylbutazone, oxyphenbutazone.
If the patient has experienced an allergic reaction or other immunological reaction to other pyrazolones and pyrazolidines or other painkillers, there is a high risk of a similar reaction to Domilgan drops.

Severe hypersensitivity reactions
The risk of severe hypersensitivity reactions is higher during treatment with Domilgan drops in the following circumstances:

• allergy to painkillers and anti-rheumatic drugs manifesting as, for example, itching and swelling (urticaria, angioedema) (analgesic asthma syndrome or intolerance to painkillers manifesting as urticaria, angioedema — see section 2 "When not to use Domilgan"),
• asthma attacks caused by bronchiolar constriction (bronchial asthma), especially if accompanied by inflammation of the nasal mucosa and sinuses (sinusitis) and nasal polyps,
• chronic urticaria,
• allergies or intolerance to preservatives (benzoates) or dyes (tartrazine),
• alcohol intolerance (lacrimation, sneezing and intense facial flushing after drinking small amounts of alcohol), which may indicate previously unrecognized intolerance to painkillers (see section 2 "When not to use Domilgan drops").

Domilgan drops may be administered to patients at increased risk of hypersensitivity reactions only after a careful benefit-risk assessment (see section 2 "When not to use Domilgan drops"). In such cases, the patient must be under strict medical supervision, with the possibility of emergency intervention.
Particularly in patients with allergies, anaphylactic shock may occur (see section 4).
Therefore, particular caution is advised when using the medicine in patients with asthma or predisposition to hypersensitivity reactions.

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 in association with metamizole treatment.
If the patient develops any of these symptoms related to severe skin reactions listed in section 4, treatment with metamizole must be discontinued and immediate medical help sought. If the patient has ever experienced severe skin reactions, Domilgan must never be used again in the future (see section 4).

Liver function disorders
Cases of hepatitis have been reported in patients taking metamizole, with symptoms appearing from several days to several months after starting treatment.
Treatment with Domilgan must be discontinued and medical advice sought if the patient develops symptoms related to liver dysfunction, such as: malaise (nausea or vomiting), fever, fatigue, loss of appetite, dark urine, pale stools, jaundice of the skin or sclera, itching, rash, or upper abdominal pain. The doctor will check the patient's liver function.
The patient should not take Domilgan if he or she previously used any medicinal products containing metamizole and experienced liver-related adverse effects.

Low blood pressure (isolated hypotensive reactions)
During treatment with Domilgan, a decrease in blood pressure may occur (see section 4).
The risk of such reactions increases:

• if the patient has low blood pressure (pre-existing hypotension), severe dehydration, poor circulation, or is in the early stages of circulatory failure (e.g. in case of myocardial infarction or severe trauma),
• if the patient has high fever.

Careful consideration of treatment, close monitoring, and, if necessary, preventive measures (e.g. circulatory stabilization) are required to reduce the risk of hypotension.
Domilgan drops may be used only when circulatory parameters are carefully monitored, and hypotension must be strictly avoided if the patient has, for example:

• severe coronary artery disease,
• cerebral vasospasm.

Patients with impaired renal or hepatic function
Domilgan should be used in patients with impaired renal or hepatic function only after careful consideration of benefit versus risk and with appropriate precautions (see section 3, subsection "Patients with impaired renal or hepatic function").

Effect on diagnostic tests
Before undergoing laboratory tests, inform the doctor about the use of Domilgan, as metamizole may affect the results of certain tests (e.g. measurement of creatinine, lipid, HDL cholesterol or uric acid levels).

Children and adolescents
The medicine should not be administered to children under 3 months of age or weighing less than 5 kg due to insufficient clinical data.

Domilgan and other medicines
Inform your doctor or pharmacist about all medicines currently taken or recently used, as well as any medicines planned for future use.
In particular, inform your doctor about the following medicines, as their blood concentrations and possibly their effectiveness may be reduced:

• bupropion, a medicine used to treat depression or as an aid in smoking cessation,
• efavirenz, a medicine used to treat HIV/AIDS infection,
• methadone, a medicine used in the treatment of addiction to illicit narcotic drugs (so-called opioids),
• valproate, a medicine used to treat epilepsy or bipolar affective disorder,
• cyclosporine, a medicine used to suppress the immune system,
• tacrolimus, a medicine used to prevent organ rejection in transplant patients,
• sertraline, a medicine used to treat depression.

The effectiveness and (or) blood concentration of these medicines should be monitored by the doctor.
In particular, inform your doctor about the following medicines that may interact with Domilgan drops, or that may be affected by Domilgan drops:

• methotrexate, a medicine used to treat cancer or rheumatic diseases. Concurrent use may increase the harmful effect of methotrexate on the haematopoietic system, especially in elderly patients. Therefore, combination of these medicines should be avoided.
• acetylsalicylic acid, taken in low doses for cardiovascular protection. Concurrent use may reduce the effect of acetylsalicylic acid on platelets.
• chlorpromazine, a medicine used to treat psychiatric disorders. Concurrent use may cause a significant drop in body temperature (severe hypothermia).

Active substances from the pyrazolone group, to which Domilgan drops belong, may cause interactions with certain medicines:

• anticoagulants (medicines that inhibit blood clot formation),
• captopril, a medicine used to treat hypertension and certain heart diseases,
• lithium, a medicine used to treat psychiatric disorders,
• diuretics, e.g. triamterene,
• antihypertensive medicines.
  The extent to which Domilgan drops cause such interactions is unknown.

Domilgan with food, drink and alcohol
Do not consume alcohol during treatment with Domilgan.

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to have a child, she should consult a 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 that the benefit and risks associated with taking the medicine are carefully considered.
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 both mother and child (bleeding, premature closure of a vital blood vessel in the child, the so-called ductus arteriosus Botalli, which normally closes only after birth).

Breastfeeding
Metamizole metabolites pass into breast milk in significant amounts, and 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, breastfeeding should be interrupted and milk expressed and discarded for 48 hours after administration of the medicine.

Driving and operating machinery
At the recommended dosage range, no adverse effects affecting reaction ability or concentration have 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 tasks involving risk should be avoided. This particularly applies to concomitant use with alcohol.

Domilgan contains sodium
The medicine contains 34.52 mg of sodium (main component of table salt) per ml of solution (20 drops).
This corresponds to 1.7% of the maximum recommended daily dietary sodium intake for adults. This should be taken into account if the patient is on a low-sodium diet.

Domilgan contains glucose (flavouring ingredient)
If the patient has previously been diagnosed with intolerance to certain sugars, he or she should consult a doctor before taking the medicine.

3. How to use Domilgan

This medicine should always be used as recommended by the doctor. If in doubt, consult
your doctor.
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 (or) fever should always be used. The
treating physician will advise the patient on how to take Domilgan.
The table below provides 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 distinct effect can be expected within 30 to 60 minutes after oral administration.
Use in children and adolescents
For pain treatment in children and adolescents up to 14 years of age, Domilgan may be administered at a single dose of 8 to 16 mg per kilogram of body weight (see table above). In the case of fever in children, a dose of Domilgan of 10 mg per kilogram of body weight is usually sufficient:

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

Patients with impaired renal or hepatic function
Due to reduced elimination rate in patients with impaired renal or hepatic function, repeated administration of high doses should be avoided. For short-term use, dose adjustment is not required. There is no experience regarding long-term use.

Method of administration
Oral administration.
It is recommended to take the drops with a small amount of water (approximately ½ glass).
The medication may be taken regardless of meals.

To open the bottle, unscrew the cap by turning it counterclockwise. Then, turn the bottle upside down so that the opening faces downward. If the drops do not flow immediately, gently tap the bottom of the bottle with a finger. The drops will then flow at regular intervals, allowing precise dose measurement.
After use, tightly close the cap by turning it clockwise. Store the bottle in the cardboard box.

Duration of treatment
The duration of treatment depends on the type and severity of symptoms and should be determined by a physician.
Do not use analgesic medications for longer than 3 to 5 days unless otherwise advised by a physician.

Overdose of Domilgan
If a dose higher than recommended has been taken, seek immediate medical advice from a physician or pharmacist.

• In case of overdose, symptoms may include nausea, vomiting, abdominal pain, dizziness, drowsiness, loss of consciousness, hypotension, circulatory collapse, worsening of kidney function up to acute renal failure, seizures, and tachycardia.

Note: After ingestion of very high doses, excretion of a harmless metabolite (rubazonic acid) may cause red discoloration of urine.

If the patient forgets to take Domilgan drops
Do not take a double dose if the previous dose was missed.
If there are any further doubts concerning the use of this medication, consult a physician or pharmacist.

4. Possible adverse reactions

Like any medicine, this medicinal product can cause adverse reactions, although not everyone will experience them.
Adverse reactions that may have serious consequences, requiring immediate discontinuation of Domilgan drops and prompt contact with a physician.
If any of the following adverse reactions occur suddenly or progress rapidly in a patient, immediate medical advice must be sought. Some adverse reactions (e.g. severe hypersensitivity reactions, severe skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis, agranulocytosis, pancytopenia) may be life-threatening. Under no circumstances should Domilgan drops be used without medical supervision. Timely discontinuation of the drug may be crucial.
If symptoms of agranulocytosis, pancytopenia or thrombocytopenia (see below) occur, Domilgan treatment must be stopped immediately and the physician will recommend a blood count examination (including blood smear). Treatment must be discontinued immediately, without waiting for laboratory test results.
Domilgan must be discontinued and a physician contacted immediately if any of the following symptoms occur:

• 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".

Other possible adverse reactions:
Uncommon adverse reactions (occur in fewer than 1 in 100 people)

• Purple to dark red skin rash, sometimes with blisters (drug eruption),
• Excessive decrease in blood pressure (isolated hypotensive reaction), probably due to the direct effect of the drug and not accompanied by other hypersensitivity symptoms. Such a reaction causes a significant drop in blood pressure only rarely. The risk of decreased blood pressure may be increased in patients with very high fever (hyperpyrexia). Typical symptoms of a significant drop in blood pressure include: increased heart rate, pallor, tremor, dizziness, nausea and loss of consciousness.

Rare (occur in fewer than 1 in 1,000 people)

• Allergic reactions (anaphylactoid or anaphylactic reactions). Typical symptoms of mild reactions may include: burning sensation in the eyes, cough, nasal symptoms, nasal congestion, chest pain, skin redness (especially of the face and head), urticaria and facial swelling, and rarely nausea and stomach cramps. Particularly notable symptoms include a feeling of warmth on and under the tongue, and especially in the palms and soles. Such milder reactions may progress to more severe forms, with generalized urticaria, severe angioedema (including in the larynx), severe bronchospasm (spastic narrowing of the lower airways), increased heart rate (sometimes decreased), cardiac arrhythmias, decreased blood pressure (sometimes preceded by an increase), loss of consciousness and circulatory shock. These reactions may occur even after previous uneventful use of the drug and may be life-threatening, sometimes even fatal. In patients with analgesic-induced asthma syndrome, allergic reactions manifest as asthma attacks (see section 2 "When not to use Domilgan").

• Decrease in white blood cell count (leukopenia),

• Skin rash (e.g. maculopapular rash).

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

• Marked decrease in certain white blood cells (agranulocytosis), including fatal cases, or decreased platelet count (thrombocytopenia). These reactions are probably immunological. They may also occur even if metamizole was previously administered without complications. Symptoms of agranulocytosis: fever, chills, sore throat, difficulty swallowing, and inflammatory conditions of the oral cavity, nose, throat, genital organs or anus. However, in patients receiving antibiotics (medicines used for bacterial infections), these symptoms may be less pronounced. Erythrocyte sedimentation rate is markedly increased, while lymph nodes are usually only slightly enlarged or not at all.

Symptoms of thrombocytopenia include, for example, increased tendency to bleeding and petechiae (pinpoint bleeding into the skin and mucous membranes).

• Asthma attacks (shortness of breath caused by bronchiolar constriction),
• Development of extensive blisters and skin lesions (bullous erythema multiforme (Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyell's syndrome),
• Worsening of kidney function, in some cases with absence or very low volume of urine output (oliguria or anuria), excretion of blood proteins in urine (proteinuria) or acute kidney failure; kidney inflammation (acute interstitial nephritis).

Frequency unknown (frequency cannot be estimated from available data)

• Anaphylactic shock,
• Myocardial infarction occurring during an allergic reaction (Kounis syndrome),
• Decreased blood volume with accompanying bone marrow dysfunction (aplastic anaemia), decreased number of white and red blood cells and platelets (pancytopenia), including cases with fatal outcome. Symptoms of pancytopenia and aplastic anaemia include: general malaise, infections, persistent fever, bruising, bleeding and pale skin.
• Cases of gastrointestinal bleeding have been reported,
• Hepatitis, yellowing of the skin and whites of the eyes, increased liver enzyme activity in blood,
• Severe skin reactions.

Metamizole should be discontinued and immediate medical assistance sought if the patient experiences any of the following severe adverse reactions:

• Reddish, flat lesions on the trunk in the shape of a target or circular, often with blisters in the center, skin peeling, oral, pharyngeal, nasal, genital or ocular ulcers. Such severe skin rashes may be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
• Extensive rash, high body temperature and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).

Excretion of a harmless metabolite of metamizole (rubazonic acid) may cause red discoloration of urine.
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform a physician, pharmacist or nurse. 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
Phone: +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

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "EXP".
The expiry date refers to the last day of the stated month.
No special temperature storage requirements for this medicinal product.
Store in the original packaging to protect from light.
After first opening, do not use beyond 6 months.
Do not use this medicine if you notice any change in the appearance of the solution.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the package and other information

What Domilgan contains
The active substance is metamizole sodium monohydrate.
Each mL (20 drops) contains 500 mg of metamizole sodium monohydrate.
1 drop contains 25 mg of metamizole sodium monohydrate.
The other ingredients are: sodium citrate, sodium cyclamate, sodium saccharin, citric acid.
Strawberry flavour:
Flavouring substances (cis-3-hexenol, furaneol, maltol, methyl cinnamate, ethyl 2-methylbutyrate, ethyl caproate, 2-methylbutyric acid, ethyl butyrate, trans-2-hexenol, gamma-decalactone)
Natural flavouring substances (Caproic acid Nat)
Carrier (anhydrous glucose syrup, corn, gum arabic, silicon dioxide)
Purified water

What Domilgan looks like and contents of the pack
Oral drops, solution
A clear, light yellow solution.
Orange glass bottle type III with HDPE cap, with LDPE dropper, in a cardboard box.
Domilgan is available in 20 mL (400 drops) pack size.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Solinea Sp. z o.o.
Elizówka, ul.Szafranowa 6
21-003 Ciecierzyn
Tel. + 48 81 463-48-82

Manufacturer
Chemax Pharma Ltd
8A, Goritsa Str, Sofia
1618, Bulgaria