Package leaflet: Information for the user

Hydroxycarbamide Aurobindo 500 mg hard capsules

Generic medicine
Please read all of this leaflet carefully before taking 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 yours, 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

What Hydroxycarbamide Aurobindo is and what it is used for
What you need to know before taking Hydroxycarbamide Aurobindo
How to take Hydroxycarbamide Aurobindo
Possible side effects
How to store Hydroxycarbamide Aurobindo
Contents of the pack and other information

1. What Idrossicarbamide Aurobindo is and what it is used for

Idrossicarbamide Aurobindo contains the active substance hydroxycarbamide, which belongs to a group of
medicines used in certain blood disorders that interfere with the growth of tumour cells.
This medicine is used for the treatment of adults and has been prescribed by your doctor for the treatment of
blood disorders: chronic myeloid leukaemia, essential thrombocythaemia, and polycythaemia vera.

2. What you need to know before taking Idrossicarbamide Aurobindo

Do not take Idrossicarbamide Aurobindo

if you are allergic to hydroxycarbamide or to any of the other ingredients of this medicine listed in section 6;
if your blood cell count is too low (bone marrow suppression, leukopenia, thrombocytopenia, severe anemia);
if you are pregnant or breastfeeding;
severe liver impairment (Child-Pugh class C);
severe renal impairment (CrCL <30 ml/min);
concomitant use of antiretroviral medicines (which inhibit or destroy a retrovirus such as HIV), e.g. didanosine and stavudine (a decrease in white blood cell count may occur);
in combination with the yellow fever vaccine (see section “Other medicines and Idrossicarbamide Aurobindo”).

Warnings and precautions
Talk to your doctor or pharmacist before taking Idrossicarbamide Aurobindo.
Treatment with hydroxycarbamide requires careful monitoring. You will undergo blood tests before and during treatment to ensure you have an adequate number of blood cells and sufficient kidney and liver function to receive this medicine. Blood tests are usually performed once a week.
If a reduction in red blood cells (anemia) occurs before or during treatment, red blood cell transfusions may be given when necessary. If hemolytic anemia (a condition in which red blood cells are destroyed faster than they can be produced) is detected during blood tests, your doctor will stop treatment with Idrossicarbamide Aurobindo.
This medicine should be avoided in combination with live attenuated vaccines (for yellow fever vaccine, see section “Do not take Idrossicarbamide Aurobindo”): measles, rubella, mumps, polio, tuberculosis, varicella, as well as with phenytoin and fosphenytoin (medicines used to treat epilepsy).
Potentially fatal hepatotoxicity and pancreatitis, as well as severe peripheral neuropathy, have been reported in HIV-infected patients who received hydroxycarbamide in combination with antiretrovirals, particularly didanosine and stavudine (see section “Other medicines and Idrossicarbamide Aurobindo”).
You should drink plenty of fluids during treatment.
If you have kidney and/or liver problems, inform your doctor before starting treatment with this medicine.
If you receive long-term treatment with hydroxycarbamide, secondary leukemia may develop. It is currently unknown to what extent this is due to the underlying disease or to treatment with hydroxycarbamide.
Skin cancer has been reported in patients treated with long-term hydroxycarbamide. You should protect your skin from sunlight and regularly perform self-examinations of your skin during treatment and after discontinuation of hydroxycarbamide therapy. Your doctor will also examine your skin during routine follow-up visits.
If you have diabetes and are using a continuous glucose monitoring (CGM) system to check your blood glucose, hydroxycarbamide (also known as hydroxyurea) may cause falsely elevated glucose readings by certain sensors. This could lead to administration of more insulin than needed, resulting in low blood sugar (hypoglycemia). Consult the doctor who prescribed your CGM to determine whether it is safe to use concurrently with Idrossicarbamide Aurobindo.

Children and adolescents
Safety and efficacy have not been established in children.

Other medicines and Idrossicarbamide Aurobindo
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
If you have previously received or are still receiving similar medicines or radiation therapy, side effects may occur more frequently and be more severe. These include mainly reduced blood cell counts (impaired bone marrow function), inflammation of the stomach lining, and skin inflammation.
Previous or concurrent radiation therapy may cause skin redness and irritation.
This medicine must not be used in combination with the yellow fever vaccine (see section “Do not take Idrossicarbamide Aurobindo”).
Combination of this medicine with live attenuated vaccines (except for the yellow fever vaccine, see section “Do not take Idrossicarbamide Aurobindo”) such as measles, rubella, mumps, polio, tuberculosis, and varicella should be avoided. Vaccination with a live vaccine may cause serious infections.
Idrossicarbamide Aurobindo should also be avoided in combination with phenytoin and fosphenytoin (medicines used to treat epilepsy), with didanosine (with or without stavudine), and other antiretrovirals (medicines used to treat HIV infection) (see “Warnings and precautions”).

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

Pregnancy
There is a risk of harmful effects on the developing baby. Therefore, you must not take this medicine during pregnancy.
You must use an effective method of contraception before starting treatment, during treatment, and for six months after stopping treatment. If you become pregnant while taking or after stopping this medicine, contact your doctor immediately.

Breastfeeding
Idrossicarbamide Aurobindo must not be taken during breastfeeding. The active substance of Idrossicarbamide Aurobindo passes into breast milk. Consult your doctor for advice.

Fertility
Men are advised to use an effective method of contraception during treatment and for at least three months after stopping treatment. Speak to your doctor about the possibility of sperm preservation before starting treatment.

Driving and using machines
Your reaction ability may be impaired during treatment with Idrossicarbamide Aurobindo. Keep this in mind when activities requiring high attention are involved, such as driving or operating machinery.

Idrossicarbamide Aurobindo contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking this medicine.

Idrossicarbamide Aurobindo contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per capsule, i.e., essentially “sodium-free”.

3. How to take Idrossicarbamide Aurobindo

Take Idrossicarbamide Aurobindo exactly as prescribed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Adults
In chronic myeloid leukemia, continuous treatment is recommended (20 to 30 mg/kg body weight as a single daily dose). The dose should then be individually adjusted based on the white blood cell count.
In polycythemia vera, the usual starting dose is 15–20 mg/kg body weight per day. The dose should then be individually adjusted based on blood cell counts.
In essential thrombocythemia, the usual starting dose is 15 mg/kg body weight per day, with individual dose adjustments based on blood cell counts.
Elderly patients
Elderly patients may be more sensitive to hydroxycarbamide and may require a lower dose.
The capsules must be swallowed whole and must not be broken up in the mouth. The capsules should be handled with care. You should wear gloves or wash your hands thoroughly after handling them. Although the risks to the fetus are minimal, pregnant women should avoid handling the capsules.
To remove the capsule from the blister pack:

press on one side of the capsule, pushing it through the aluminum foil;
do not apply pressure to the center of the capsule, as this may cause it to break.

If you take more Idrossicarbamide Aurobindo than you should
If you have taken more of this medicine than prescribed, contact your doctor or go to a hospital immediately. Symptoms affecting the mucous membranes and skin may occur.
If you forget to take Idrossicarbamide Aurobindo
It is important to follow exactly the prescribed dosage regimen.
Do not take a double dose to make up for a missed dose. If you have missed a single dose, continue treatment as prescribed. If you have missed several doses, continue treatment as prescribed but contact your doctor for further advice.
If you stop taking Idrossicarbamide Aurobindo
If you stop taking hydroxycarbamide, your condition may worsen. Treatment with hydroxycarbamide should only be stopped or suspended on the advice of your doctor.
If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Contact your doctor immediately if you experience symptoms such as:

Fever, cough or breathing problems, which may be signs of a serious lung disease (frequency not known).
High fever (> 39°C) with stomach, lung, muscle, liver, skin, and heart problems within 6 weeks of taking Hydroxycarbamide Aurobindo (rare frequency).
Very common (may affect more than 1 in 10 people)
Absence or low number of sperm in semen (azoospermia or oligospermia), usually reversible.
Decrease in blood cells (reduced bone marrow function), particularly white blood cells (leucopenia), including types of white blood cells that help the body fight infections (reduction in CD4 lymphocytes), red blood cells (anaemia), and platelets (thrombocytopenia).
Feeling unwell (nausea), vomiting, loss of appetite (anorexia), mouth ulcers (stomatitis), diarrhoea, constipation, inflammation of mucous membranes (mucositis), digestive problems (dyspepsia).
In combination with certain HIV treatments: inflammation of the pancreas (pancreatitis) with stomach or abdominal pain.
Drug-induced fever, chills, feeling unwell (malaise), weakness, loss of energy.
Skin ulcers.
Skin rash with spots and blisters (maculopapular rash), facial redness, redness of hands and feet (hand-foot syndrome).
Skin changes such as thinning of the skin; darkening and deterioration of nails and skin, blackening and necrosis of the skin.
Hair loss (alopecia).
Temporary kidney problems with increased levels of certain blood parameters such as uric acid, urea, and creatinine.
Pain when urinating.
Inflammation of blood vessels in the skin (cutaneous vasculitis).
Dermatomyositis.
Papular rash.

Common (may affect up to 1 in 10 people)

Skin cancer.
Increased liver enzymes.
Inflammation of the liver (hepatitis) causing flu-like symptoms, including fatigue, loss of appetite, fever, pain and feeling unwell/discomfort, pressure or pain under the right ribs, possibly including yellowing of the skin or eyes.
Problems with bile flow (cholestasis). Bile produced by the liver to aid digestion may not flow properly. Accumulation of bile can cause itching, yellow skin, very dark urine, and very pale stools.
Neurological disorders including headache, dizziness, drowsiness, disorientation, hallucinations, seizures, and peripheral neuropathy.
In combination with certain HIV treatments: numbness, tingling, or pain in arms and legs (peripheral neuropathy) and yellowing of the skin (hepatotoxicity).
Rare (may affect up to 1 in 1,000 people)
Metabolic complications due to breakdown products of tumour cells (tumour lysis syndrome).
Tissue decay and death (gangrene).

Not known (frequency cannot be estimated from available data)

Fever, cough or breathing problems, which could be signs of a serious lung disease; allergic inflammation of the alveoli.
Excessive breakdown of red blood cells (haemolytic anaemia).
Nail pigmentation.
Cutaneous lupus erythematosus, systemic lupus erythematosus (a condition in which the body's immune system attacks normal tissues, causing symptoms such as joint swelling, fatigue, and skin rashes).

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 https://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 Idrossicarbamide Aurobindo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and the outer carton after EXP.
The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines 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 Idrossicarbamide Aurobindo contains

The active substance is hydroxycarbamide. Each hard capsule contains 500 mg of hydroxycarbamide.

The other components are: monohydrate lactose, citric acid, disodium phosphate, magnesium stearate.
In the capsule cap: yellow iron oxide (E172), indigo carmine (E132), titanium dioxide (E171),
gelatin.
In the capsule body: red iron oxide (E172), titanium dioxide (E171), gelatin.
Printing ink (black): shellac, black iron oxide (E172), potassium hydroxide.

Description of the appearance of Idrossicarbamide Aurobindo and pack contents

Hard capsule.
Idrossicarbamide Aurobindo 500 mg hard capsules:
Hard gelatin capsule with an opaque green cap and pinkish-orange body, size '0', marked with 'H500' on the body, filled with white to slightly yellowish crystalline powder.
Idrossicarbamide Aurobindo hard capsules are available in blister packs containing 20 or 100 capsules.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Eugia Pharma (Malta) Ltd
Vault 14, Level 2, Valletta Waterfront, Floriana FRN 1914, Malta

Manufacturers
APL Swift Services (Malta) Ltd
HF26, Hal Far Industrial Estate, Hal Far, Birzebbugia, BBG3000, Malta
Generis Farmacêutica SA
Rua João de Deus, n. 19, Venda Nova, 2700-487 Amadora, Portugal
Arrow Génériques
26 avenue Tony Garnier, Lyon, 69007, France

This medicinal product is authorized in the European Economic Area countries under the following names:
France: Hydroxycarbamide Arrow 500 mg, gélule.
Italy: Idrossicarbamide Aurobindo
Netherlands: Hydroxycarbamide Eugia 500 mg, harde capsules
Poland: Hydroxycarbamid Eugia
Portugal: Hidroxicarbamida Generis