Milurit

Package leaflet: Information for the user

Milurit, 150 mg, tablets
Milurit, 200 mg, tablets
Allopurinolum
Please read all of this leaflet carefully before taking this medicine, because it contains important information for you.

• Keep this leaflet so that you can read it again if necessary.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual only. Do not share it with others. This medicine may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Milurit is and what it is used for

The active substance in Milurit tablets is allopurinol. Allopurinol belongs to a group of medicines known as enzyme inhibitors. These substances are effective in controlling the rate of certain processes in the body.
Milurit is used long-term to prevent gout and may also be used in other conditions associated with excess uric acid in the body, such as kidney stones and other kidney diseases, as well as in patients receiving treatment for cancer or who have disorders in the function of certain enzymes.

2. Important information before using Milurit

When not to use Milurit

• If the patient is allergic to allopurinol or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Before starting treatment with Milurit, discuss this with your doctor.
Special caution and close medical supervision may be necessary:

• If the patient belongs to the Han Chinese ethnic group or is of Thai or Korean descent.
• If the patient has liver or kidney disease. The doctor may recommend a lower dose or less frequent than daily administration. The patient will also be monitored more closely.
• If the patient has heart disease or high blood pressure and is taking diuretics and/or blood pressure-lowering medicines called ACE inhibitors.
• If an acute gout attack is currently present.
• If the patient or a close relative has haemochromatosis (a rare disorder characterised by abnormally increased absorption of iron from the gastrointestinal tract, leading to excessive iron storage, particularly in the liver).
• If the patient has thyroid disease.
• If the patient is being treated with azathioprine (an immunosuppressive medicine used to suppress the immune response), or mercaptopurine (a medicine used in leukaemias).

If in doubt whether any of the above situations apply, speak to your doctor or pharmacist.
Severe skin rashes (hypersensitivity syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported during allopurinol treatment. Skin rashes often involve ulceration of the mouth, throat, nose, genital organs, and conjunctivae (redness and swelling of the eyes). These potentially life-threatening severe skin reactions are often preceded by flu-like symptoms such as fever, headache, and body aches. The rash may progress to widespread blistering and skin peeling.
These severe skin reactions may occur more frequently in individuals of Chinese, Thai, or Korean descent. Chronic kidney disease may further increase the risk in these patients.
If a skin rash or skin symptoms occur, stop taking Milurit immediately,
seek urgent medical advice, and inform the doctor that you are taking this medicine. If severe skin rashes, hypersensitivity syndrome, Stevens-Johnson syndrome, or toxic epidermal necrolysis occur during treatment with Milurit, re-initiation of Milurit therapy is not permitted.
An acute attack of gouty arthritis may be expected early in treatment with Milurit. Therefore, the doctor may prescribe prophylactic treatment with an appropriate anti-inflammatory medicine or colchicine for at least one month.
To monitor the safety and effectiveness of Milurit treatment, the doctor may order one or more laboratory tests. These tests should be performed and the results shown to the doctor.
If the patient has been diagnosed with a tumour disease or Lesch-Nyhan syndrome, the amount of uric acid in the urine may increase. To prevent this, drink sufficient fluids to adequately dilute the urine.
If the patient has kidney stones, the stones may decrease in size during treatment and may move into the urinary tract.

Children and adolescents
Children and adolescents under 15 years of age should not use Milurit, except in cases of certain tumours (especially leukaemias) or in the treatment of certain enzymatic disorders such as Lesch-Nyhan syndrome.

Milurit and other medicines
Tell your doctor if you are currently using, have recently used, or plan to use any of the following medicines:
salicylates (used to reduce pain, fever, or inflammation, e.g. acetylsalicylic acid)
theophylline, a medicine used for breathing problems. The doctor may order blood level monitoring of theophylline, especially at the beginning of Milurit treatment or may modify the dose.
medicines used to treat seizures (epilepsy) (phenytoin)
ampicillin or amoxicillin (used for bacterial infections). Since allergic reactions are more common, patients should receive alternative antibiotics if possible.
didanosine, used in the treatment of HIV infection
vidarabine, used in the treatment of viral infections. Note: adverse effects of vidarabine may occur more frequently. Special precautions should be taken if they occur.
blood count abnormalities occur more frequently when allopurinol is taken together with cytostatic agents (e.g. cyclophosphamide, doxorubicin, bleomycin, procarbazine, alkylating halides) than when these active substances are taken separately.
Therefore, regular blood count monitoring is necessary.
if aluminium hydroxide is taken simultaneously, allopurinol may have reduced effectiveness.
An interval of at least 3 hours should be maintained between taking both medicines.
medicines used to suppress the immune response (immunosuppressive medicines), such as cyclosporine (adverse effects of cyclosporine may occur more frequently), azathioprine (used to suppress immune system function), and 6-mercaptopurine (used in the treatment of blood cancer). Concomitant administration of 6-mercaptopurine or azathioprine with allopurinol should be avoided. When 6-mercaptopurine or azathioprine is administered concomitantly with Milurit, the dose of 6-mercaptopurine or azathioprine should be reduced, as their action will be prolonged. This may increase the risk of serious blood disorders. In such cases, the doctor will closely monitor blood cell counts during treatment.
Seek immediate medical help if the patient notices any unexplained bruising, bleeding, fever, or sore throat.

• medicines used to treat diabetes (chlorpropamide). A dose reduction of chlorpropamide may be necessary, especially in patients with impaired kidney function.
• medicines used to treat heart disease or high blood pressure, such as ACE inhibitors (e.g. captopril, ramipril) or diuretics (especially thiazide diuretics or furosemide)
• medicines used to thin the blood (anticoagulants), such as warfarin, phenprocoumon, and acenocoumarol. The doctor will monitor blood clotting parameters more frequently and may reduce the dose of these medicines if necessary.
• other medicines used to treat gout, such as probenecid.

Tell your doctor or pharmacist about all medicines currently or recently taken, as well as any medicines you plan to take. This includes medicines available without a prescription, including herbal medicines. This is necessary because Milurit may affect the action of other medicines. Likewise, other medicines may affect the action of Milurit.

Pregnancy and breastfeeding
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
The safety of using Milurit during pregnancy is not sufficiently documented. Milurit may be used during pregnancy only if no safer alternative is available and the disease itself poses a risk to the mother or unborn child.

Breastfeeding
Allopurinol is excreted in the milk of breastfeeding women. Allopurinol is not recommended during breastfeeding.

Driving and operating machinery
Drowsiness, dizziness, or coordination disturbances may occur. If such symptoms occur, do not drive or operate machinery.

Milurit contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially "sodium-free".

3. How to use Milurit

This medicine should always be used exactly as prescribed by the doctor. If in doubt, consult your doctor or pharmacist.
Milurit should be taken once daily after a meal. Throughout the treatment, the patient should drink plenty of fluids (2–3 litres per day). If the daily dose exceeds 300 mg and the patient experiences gastrointestinal adverse effects such as nausea and vomiting (see section 4), the doctor may prescribe allopurinol in divided doses to reduce these effects.
Dosage should always be individually determined by the doctor.

Recommended doses
Adults
The doctor usually starts treatment with a low dose of allopurinol (e.g. 100 mg/day) to reduce the risk of adverse effects. The dose may be increased if necessary.
Recommended maintenance doses are:
100 to 200 mg daily for mild conditions, 300 to 600 mg daily for moderate conditions, and 700 to 900 mg daily for severe conditions.
If dosing in mg/kg body weight is required, use a dose of 2 to 10 mg/kg body weight/day.
Early in treatment, the doctor may prescribe an anti-inflammatory medicine or colchicine for at least one month to prevent gout attacks.

Use in children and adolescents (under 15 years)
In children under 15 years of age, Milurit is used at doses of 10 to 20 mg/kg body weight/day, up to a maximum of 400 mg/day in three divided doses. Use in children is rarely indicated, except in tumour diseases (especially leukaemias) and certain enzymatic disorders such as Lesch-Nyhan syndrome.

Elderly patients (over 65 years)
The doctor will recommend the lowest dose of Milurit that effectively controls symptoms.

If the patient has severe kidney disease
The patient may be advised to take a dose lower than 100 mg daily or to take 100 mg at intervals longer than once daily.
If the patient is dialysed two or three times weekly, the doctor may recommend a dose of 300 or 400 mg to be taken immediately after dialysis.
In kidney disease, the doctor may monitor kidney function, especially if the patient is also taking diuretics (particularly thiazide diuretics).

If the patient has liver disease
The doctor may recommend lower doses. Periodic liver function tests may be necessary, especially at the beginning of treatment.

Treatment of conditions associated with increased uric acid turnover (e.g. tumour diseases, disorders of certain enzyme functions)
It is recommended to normalise elevated uric acid levels before starting cytotoxic therapy. Adequate fluid intake is important.

Skin reactions
If skin reactions occur, allopurinol should be discontinued immediately. After resolution of mild skin reactions, treatment may be resumed at a low dose (e.g. 50 mg/day) only after careful consideration of potential risks. The dose may then be gradually increased, with monitoring for skin reactions and other possible adverse effects. If the rash recurs, the medicine must be permanently discontinued, considering the possibility of severe skin reactions (see section 4 Possible adverse effects).

Taking more Milurit than recommended
If more Milurit than recommended is taken, or if a child has swallowed tablets, contact a doctor or go immediately to the nearest hospital emergency department. Bring this leaflet, any remaining tablets, and the medicine packaging so the doctor knows which tablets were taken.
Common symptoms of overdose include nausea, vomiting, diarrhoea, or dizziness.
Until medical help is available, ensure adequate fluid intake.

Missed dose of Milurit
If a dose is missed, take it as soon as possible. However, if it is almost time for the next dose, skip the missed dose. Do not take a double dose to make up for a missed dose. Continue treatment as prescribed by the doctor.

Stopping Milurit treatment
The duration of treatment is determined by the doctor.
Do not stop taking Milurit without first consulting your doctor, unless allergic reactions or other serious adverse effects occur (see section 4).
If you have any further questions about using this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.
Adverse effects associated with the use of Milurit occur rarely in the treated patient population and are mostly mild in severity. The frequency of adverse effects increases in cases of concomitant kidney and/or liver disease.
Cases of potentially life-threatening skin rash (Stevens-Johnson syndrome, toxic epidermal necrolysis) have been reported (see section 2).
If any of the following adverse effects occur in a patient during treatment with Milurit, the medicine must be discontinued immediately and medical advice should be sought without delay.

Uncommon (may occur in up to 1 in 100 people):
Allergic reactions
Symptoms may include:

• skin rash, skin peeling, ulceration of the lips and oral cavity
• swelling of the face, hands, lips, tongue or throat
• difficulty swallowing or breathing
• very rarely sudden wheezing, palpitations, chest tightness or collapse. Do not take any more tablets unless your doctor has specifically instructed you to do so.

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

• fever and chills, headache, muscle pain (flu-like symptoms) and general malaise
• skin changes, such as ulceration of the mouth, throat, nose, or genital organs, and conjunctivitis (red, swollen eyes), widespread blisters or skin peeling
• severe hypersensitivity reactions with fever, skin rash, joint pain and abnormal blood test results or liver function tests (these may be symptoms of multi-organ hypersensitivity)

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

• severe allergic reaction causing swelling of the face or throat
• potentially life-threatening allergic reaction

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

• aseptic meningitis (inflammation of the membranes surrounding the brain and spinal cord): symptoms include neck stiffness, headache, nausea, fever or altered consciousness. If such symptoms occur, seek immediate medical attention.

Other possible adverse effects
Common (may occur in up to 1 in 10 people):

• Rash
• Increased TSH (thyroid-stimulating hormone) blood levels

Uncommon (may occur in up to 1 in 100 people):

• nausea, vomiting and diarrhoea
• abnormal liver function test results

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

• joint pain or painful swelling in the groin, armpits or neck
• jaundice (yellowing of the skin and whites of the eyes)
• liver disorders, such as hepatitis
• kidney disorders
• formation of stones in the urinary tract; symptoms may include blood in the urine and abdominal, flank or groin pain

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

• Occasionally, allopurinol tablets may affect the blood, leading to easier bruising than usual, sore throat or other signs of infection. These symptoms usually occur in people who have liver or kidney problems. Inform your doctor as soon as possible. Milurit may affect the lymph nodes.
• high temperature
• blood in the urine, kidney failure
• vomiting blood
• high levels of fats in the blood
• general malaise
• weakness, numbness of hands or feet, loss of balance, tingling, inability to move muscles (paralysis), or loss of consciousness
• headache, dizziness, drowsiness or visual disturbances
• chest pain, high blood pressure or slow heart rate
• male infertility or inability to achieve or maintain an erection
• breast enlargement in men and women
• changes in bowel habits, presence of fat in the stool
• taste disturbances
• cataract (clouding of the eye lens), macular disease of the eye
• hair loss or change in hair colour
• seizures
• depression
• fluid retention leading to swelling, particularly around the ankles
• increased thirst, fatigue, weight loss (these may be symptoms of diabetes). Your doctor may recommend a blood glucose test to determine if this is the cause.
• boils (furunculosis, small tender red lumps on the skin)
• muscle pain

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

• abdominal pain
• lichenoid skin eruption (itchy reddish-purple skin rash and/or thread-like white-grey lines on mucous membranes)

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
ul. 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 effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps provide more information on the safety of this medicine.

5. How to store Milurit

Keep this medicine out of the sight and reach of children.
No special storage instructions apply.
Do not use this medicine after the expiry date (month, year) stated on the outer carton after: "expiry date". The expiry date refers to the last day of the stated month.
Medicines should 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 Milurit contains
The active substance is allopurinol.
Tablets 150 mg: each tablet contains 150 mg of allopurinol.
Tablets 200 mg: each tablet contains 200 mg of allopurinol.
The other ingredients are: microcrystalline cellulose, sodium carboxymethyl starch (type A), gelatin,
colloidal anhydrous silicon dioxide, magnesium stearate.

What Milurit looks like and contents of the pack
Appearance:
Tablets 150 mg: white or greyish, oval tablets, engraved with the code "E353" on one side and a division line on the other side. The tablet can be divided into equal doses.
Tablets 200 mg: white or greyish, oval tablets, engraved with the code "E354" on one side and a SNAP division line on the other side. The tablet can be divided into equal doses.
Pack:
30, 50, 60, 70, 80, 90, 100 or 120 tablets in a brown glass bottle type III, closed with a PE cap and a tamper-evident seal, packed in a cardboard box.

Marketing Authorisation Holder
PROTERAPIA sp. z o.o.
ul. Komitetu Obrony Robotników 45 D
02-146 Warsaw
Poland

Manufacturer
EGIS Pharmaceuticals PLC.
Mátyás király u. 65
9900 Körmend
Hungary

For further information, please contact the representative of the Marketing Authorisation Holder in Poland.
Name: PROTERAPIA sp. z o.o.
ul. Komitetu Obrony Robotników 45 D
02-146 Warsaw
Poland
Telephone: +48 22 417 92 00