Onco carbide

Package leaflet: Information for the user

Onco Carbide 500 mg hard capsules

Hydroxycarbamide (hydroxyurea)
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 their symptoms are the same as yours, as it may 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 Onco Carbide is and what it is used for
2. What you need to know before taking Onco Carbide
3. How to take Onco Carbide
4. Possible side effects
5. How to store Onco Carbide
6. Contents of the pack and other information

1. What Onco Carbide is and what it is used for

Onco Carbide contains the active substance hydroxycarbamide (also known as hydroxyurea), which belongs to a group of medicines that interfere with the growth of tumours (antineoplastic medicines).
Onco Carbide is indicated for:

• chronic myeloid leukaemia (a blood disorder caused by malfunction of the bone marrow, the organ responsible for producing all blood cells);
• chronic myeloproliferative syndromes (blood disorders causing excessive growth of certain blood cells):
  • essential thrombocythaemia (a disorder causing too many platelets in the blood);
  • polycythaemia vera (a disorder causing too many red blood cells in the blood);
  • idiopathic myelofibrosis (a chronic bone marrow disorder with proliferation of immature cells and excessive deposition of fibrous tissue in the bone marrow);
• primary squamous cell carcinomas of the head and neck, excluding the lips (malignant tumours affecting the head and oral cavity), in combination with 5-Fluorouracil and radiotherapy;
• homozygous sickle cell anaemia (a blood disorder in which red blood cells, a type of blood cell, assume an abnormal shape resembling a crescent or sickle).

2. What you need to know before using Onco Carbide

Do not use Onco Carbide

• if you are allergic to hydroxycarbamide (hydroxyurea) or to any of the other ingredients of this medicine (listed in section 6);
• if you have severe impairment of bone marrow function (severe myelosuppression):
  • leucopenia (severe reduction in the number of white blood cells in the blood, less than 2,500/mm³);
• thrombocytopenia (severe reduction in the number of platelets in the blood, less than 100,000/mm³);
• anaemia (severe reduction in haemoglobin in the blood, the substance that carries oxygen in the blood);
  • if you are pregnant or breastfeeding (see section “Pregnancy, breastfeeding and fertility”);
  • if you have received the yellow fever vaccine.

Warnings and precautions
Talk to your doctor or pharmacist before taking Onco Carbide.
In particular, inform your doctor:

• if you have undergone radiotherapy, as you may experience worsening of radiation erythema (skin irritation and redness that may occur after radiotherapy) and reduced bone marrow function;
• if you have undergone antineoplastic therapy (treatment with medicines that fight tumours), as you may develop reduced bone marrow function;
• if you have severe kidney function impairment;
• if you have severe liver disorders;
• if you have severe anaemia. In this case, your doctor will perform blood transfusions before starting treatment with this medicine. During treatment with this medicine, your doctor will monitor your anaemia;
• if you have diabetes and are using a continuous glucose monitoring system (CGM) to check your blood glucose, hydroxycarbamide (also known as hydroxyurea) may cause falsely elevated glucose readings by some sensors. This could lead to administration of more insulin than needed, resulting in low blood sugar (hypoglycaemia). Consult your doctor who prescribed the CGM to determine whether it is safe to use it concurrently with Onco Carbide.

If you are a woman of childbearing age, you must use an effective method of contraception during
treatment with Onco Carbide and for 6 months after the end of treatment (see section 2
“Pregnancy, breastfeeding and fertility”).
If you are a man of childbearing age, you must use an effective method of contraception during
treatment with Onco Carbide and for at least 3 months after the end of treatment. In addition, due to the risk of
reduced fertility, your doctor may suggest that you preserve your sperm before starting
treatment (see section 2 “Pregnancy, breastfeeding and fertility”).
During treatment with Onco Carbide, your doctor will monitor your levels of haemoglobin (the
substance that carries oxygen in the blood, present in red blood cells), white blood cells and
platelets in your blood through appropriate tests.
If haemolytic anaemia (a disorder in which red blood cells are destroyed faster than they can be
produced) is detected during blood tests, your doctor will discontinue treatment with Onco Carbide.
Long-term treatment with hydroxycarbamide (hydroxyurea) may cause undesirable effects affecting
the skin and mouth (see section 4 “Possible side effects”).
Most of these, such as pigmentation (discoloration) of the nails, skin and mouth, cutaneous xerosis (dry skin), mouth ulcers and ichthyosis (a skin disease characterised by dry, thickened, scaly skin) do not require discontinuation of treatment.
Skin ulcers may occur in cases of chronic myeloproliferative syndromes with prolonged high-dose treatment, more frequently in elderly patients or women, and require temporary or permanent discontinuation of therapy (see section 4 “Possible side effects”).
Skin cancer has been reported in patients treated with hydroxycarbamide (hydroxyurea) over the long term. You must protect your skin from sunlight and monitor it regularly during treatment and after stopping hydroxycarbamide (hydroxyurea) therapy. Your doctor will also examine your skin during routine check-ups.
Other medicines and Onco Carbide
Inform your doctor or pharmacist if you are taking, have recently taken or might take any other
medicines.
In particular, inform your doctor:

• if you are taking other myelosuppressive medicines (to reduce the number of red and/or white blood cells or platelets);
• if you are undergoing radiotherapy, as this may increase the risk of bone marrow depression or other adverse effects;
• if you are taking or have taken interferon (a medicine used in case of infections caused by certain viruses), as you may develop vasculitis (inflammation of blood vessels);
• if you are receiving inactivated vaccines (e.g. polio vaccine);
• if you are using immunosuppressants (medicines that suppress the body's immune response);
• reverse transcriptase inhibitors (medicines used to treat HIV infections);
• if you are taking antiretroviral medicines (reverse transcriptase inhibitors, nucleoside analogues in case of HIV);
• cyclosporine and tacrolimus (medicines administered after organ transplantation).

Pregnancy, breastfeeding and fertility
Contraception
If you are a man or woman of childbearing age, you must use an effective method of contraception during
treatment with Onco Carbide and for at least 3 and 6 months, respectively, after stopping
treatment.
Pregnancy
Hydroxycarbamide (hydroxyurea) crosses the placenta; therefore, do not take this medicine if
you are pregnant (see section “Do not take Onco Carbide”) as it may harm the foetus. However, if necessary, your doctor may prescribe it after informing you of the potential risks to the foetus.
If you are pregnant and caring for someone taking Onco Carbide, avoid contact with the powder contained in the capsule (see section “How to take Onco Carbide”).
Breastfeeding
Hydroxycarbamide (hydroxyurea) passes into breast milk; therefore, you must not breastfeed while taking
this medicine (see section “Do not take Onco Carbide”).
Men who wish to have children should be informed of the risk of reduced fertility.
Driving and use of machines
No studies on the ability to drive and use machines have been conducted.
It is not known whether this medicine affects attention or reaction time.
Onco Carbide contains lactose.
If your doctor has diagnosed you with an intolerance to certain sugars, contact him/her before taking
this medicine.
Onco Carbide contains sodium.
This medicine contains less than 1 mmol (23 mg) of sodium per single dose (1 capsule), i.e.
essentially “sodium-free”, and approximately 1.5 mmol (about 34.9 mg) of sodium (the main component
of table salt) per 2000 mg dose (4 capsules), equivalent to 1.7% of the maximum recommended daily dietary intake for an adult.

3. How to take Onco Carbide

Take this medicine exactly as stated in this leaflet or as directed by your doctor or pharmacist. If you are in doubt, consult your doctor or pharmacist.
Your doctor will determine the dose of Onco Carbide based on your health condition. Your doctor will perform regular blood tests and, if necessary, may interrupt the treatment and possibly reduce the dose of Onco Carbide.
Your doctor may prescribe you to take the medicine either daily or intermittently to reduce toxic effects that may occur during treatment with Onco Carbide or in combination with radiotherapy.

• In chronic myeloid leukemia and chronic myeloproliferative syndromes, the recommended dose is 20–30 mg/kg orally in one or two daily doses. The duration of treatment is at least six weeks. Your doctor may decide to continue the therapy if considered appropriate.
• In sickle cell anemia, the recommended dose is 15–30 mg/kg orally in one or two daily doses. The duration of treatment is at least 6–8 months. In primary carcinomas of the head and neck (excluding lips), the recommended dose ranges from 1000 to 2000 mg daily orally, usually divided into two daily doses.

In solid tumors, your doctor may prescribe a treatment regimen of 80 mg/kg orally as a single daily dose.
Instructions for individuals who must handle this medicine but are not taking it.
If you need to handle the capsules, wear disposable gloves and wash your hands before and after touching the capsules.
If a capsule is opened, any excess powder should be absorbed with absorbent paper, which should then be sealed in a closed plastic bag.
If you are pregnant and assisting someone taking Onco Carbide, you must not come into contact with the powder inside the capsule.
Elderly patients
If you are elderly, you may be more sensitive to Onco Carbide, and therefore your doctor may prescribe a lower dose.
Duration of treatment
You must continue taking Onco Carbide for as long as your doctor instructs.
If you take more Onco Carbide than you should
In case of accidental ingestion or overdose of Onco Carbide, contact your doctor immediately or go to the nearest hospital.
If you have taken an excessive dose of this medicine, your doctor may temporarily interrupt the treatment, perform monitoring tests, and initiate appropriate therapy.
If you forget to take Onco Carbide
Do not take a double dose to make up for the missed capsule.
If you stop taking Onco Carbide
If you have any doubts about using this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience the following side effects during treatment with Onco Carbide, your doctor will STOP the treatment:

• skin lesions (cutaneous ulcers), located near the malleoli (ankle bones) or in the legs. Discontinuation of Onco Carbide generally leads to complete healing and disappearance of pain (see section “Warnings and precautions”);
• effects related to blood: severe bone marrow suppression (reduction in white blood cells, platelets, and red blood cells). Additionally, you may experience the following side effects:

Other effects related to blood

• secondary leukaemia (blood cancer that may occur following long-term treatment);
• haemolytic anaemia (frequency not known).

Effects related to mouth, stomach and intestine

• stomatitis (inflammation of the mouth);
• anorexia (loss of appetite);
• nausea;
• vomiting;
• diarrhoea;
• constipation.

Effects related to kidneys, bladder and genital organs

• reduced kidney function (resulting in increased levels of uric acid, nitrogen, and creatinine in the blood);
• dysuria (difficulty urinating);
• amenorrhoea (absence of menstruation);
• azoospermia (absence of spermatozoa in seminal fluid in men), oligospermia (low sperm count in seminal fluid in men). Azoospermia and oligospermia are usually reversible, meaning sperm counts return to normal.

Effects related to skin and mucous membranes

• maculopapular rash (skin eruptions with red spots and small raised areas on the skin);
• facial erythema (irritation and redness of the face);
• pruritus (itching);
• hyperpigmentation (change in skin colour);
• alopecia (hair loss);
• melanonychia (damage affecting the nails causing them to become darkly pigmented);
• dry skin;
• dermo-ungual atrophy (thinning of the skin and nails);
• skin desquamation (loss of the outer layer of skin);
• skin lesions resembling dermatomyositis: erythematous (red skin) or erythematous-desquamative (red, peeling skin) skin lesions;
• skin cancer affecting certain types of skin cells (basal cell carcinoma and squamous cell carcinoma);
• skin inflammation causing red, scaly patches, sometimes associated with joint pain.

Effects related to the nervous system

• headache;
• dizziness;
• disorientation;
• hallucinations (perception of things that do not exist in reality);
• seizures (uncontrolled body movements).

Effects related to the liver

• abnormal liver function tests (changes in certain blood values that may indicate liver damage).

Effects related to the lungs and respiratory tract

• fever, cough or breathing problems, which could be signs of a serious lung disease (frequency not known).

Other effects

• Fever.

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 Onco Carbide

Keep this medicine out of the sight and reach of children.
Store at a temperature not exceeding 25°C.
Do not use this medicine after the expiry date stated on the pack after EXP. The expiry date refers to the last day of that month.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Onco Carbide contains

• The active substance is: hydroxycarbamide (hydroxyurea) 500 mg
• The other components are: lactose (see section “Onco Carbide contains lactose”); calcium citrate; disodium citrate; magnesium stearate. The components of the capsule shell are: gelatin; titanium dioxide (E171); iron oxide (E172).

Description of the appearance of Onco Carbide and contents of the pack
Onco Carbide is available as 500 mg hard capsules, packed in blisters in a carton pack containing 20 capsules.
Marketing Authorization Holder
TEOFARMA S.r.l., Via F.lli Cervi, 8 - 27010 Valle Salimbene (PV).
Manufacturer
Teofarma S.r.l., Viale Certosa, 8/A – 27100 Pavia.