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Hydroxycarbamide 500mg Capsules Hard

PACKAGE LEAFLET: INFORMATION FOR THE USER    ^oooooltooo


Hydroxycarbamide 500 mg Capsules, hard


Hydroxycarbamide


Read all of this leaflet carefully before you start taking this medicine.

•    Keep this leaflet.You may need to read it again.

•    If you have any further questions, ask your doctor or pharmacist.

•    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

•    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.


In this leaflet:

1.    What Hydroxycarbamide is and what it is used for

2.    Before you take Hydroxycarbamide

3.    Howto take Hydroxycarbamide

4.    Possible side effects

5.    Howto store Hydroxycarbamide

6.    Further information


A SANDOZ


What Hydroxycarbamide is and what it is used for


Hydroxycarbamide is used for the treatment of patients:

•    with an aggressive white blood cell disease starting at the bone marrow (chronic myeloid leukaemia) in a chronic or accelerated phase of the disease

•    with a surplus of blood platelets (essential thrombocythaemia)

•    with a surplus of certain blood cells (polycythaemia vera) associated with a high risk of vascular occlusion (thrombosis)

Hydroxycarbamide is a medicine to treat tumour diseases.


Before you take Hydroxycarbamide


Do not take Hydroxycarbamide

•    if you are hypersensitive (allergic) to

hydroxycarbamide or any of the other ingredients of hydroxycarbamide. Therapy should be discontinued if hypersensitivity to hydroxycarbamide occurs.

•    if the function of the bone marrow is considerably reduced, such as

-    reduced number of white blood cells (less than 2.5 x 109 leukocytes/l)

-    deficiency of blood platelets (less than 100 x 109 thrombocytes/l)

-    severe anaemia (reduction in red blood cells).

•    if you are pregnant or think you might be pregnant.

•    if you are breast-feeding.

•    if you are concomitantly treated with yellow fever vaccine.

Take special care with Hydroxycarbam ide

•    if you suffer from impaired liver and/or kidney function.

Only little experience is available regarding this. Special caution is therefore required during treatment with hydroxy carbamide, particularly at the beginning of therapy. The blood values as well as liver and kidney function are to be monitored by a doctor during treatment with hydroxycarbamide.

•    if you suffer from anaemia or if it occurs.

•    if you notice skin changes (for example: purple coloured rash and thinninng of the skin).

•    if you notice painful ulcers on the lower legs.

These are usually difficult to treat and can require interruption of treatment. Discontinuation of hydroxycarbamide usually enables the ulcers to slowly heal after some weeks.

•    if you receive long-term treatment in cases of excessive formation of blood cells such as polycythaemia vera (a blood disorder in which the bone marrow makes too many red blood cells) and thrombocythaemia (a disorder in which excess platelets are produced).

•    if you experience impaired blood formation in the bone marrow.

•    if you are given other anticancer drugs or radiotherapy treatment.

•    if you are concomitantly treated with live attenuated vaccines (expected yellow fever vaccines see “Do not take hydroxycarbamide”).

Even after the dose has been stabilised, the following levels in the blood needs to be observed during treatment with hydroxycarbamide:

-    content of red blood pigment

-    different types of white blood cells

-    number of blood platelets

The control interval must be adjusted to a particular individual, but is normally once a week.

It is important to monitor uric acid levels regularly. You should always drink sufficient liquid during treatment with hydroxycarbamide.

Appropriate contraceptive measures are to be taken if one partner is treated with hydroxycarbamide.

Men undergoing treatment with hydroxycarbamide should not father a child during treatment and up to 1 year afterwards.

Seek advice on sperm conservation before beginning therapy as hydroxycarbamide therapy can cause transient infertility. If pregnancy is desired, specialized counselling is recommended even after therapy.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

•    Other medicines against tumour diseases or radiotherapy

Side effects can be more intense and more common than after administration of


hydroxycarbamide alone. These side effects include the reduction of blood formation in the bone marrow, stomach and bowel complaints and inflammation in the mouth cavity. Increase in inflammatory reddening of the skin caused by previous or existing radiotherapy is possible.

Laboratory tests have shown that hydroxycarbamide enhances the toxicity of certain medicines against tumour diseases, e.g.

•    fluoropyrimidines (e.g. fluorouracil) and

•    cytarabine

It is not clear whether these interactions are additive in their toxicity during use in humans and whether the dose must be adjusted.

   Medicines against viral diseases

(nucleoside analogues - medicines used to prevent viral multiplication in infected cells and medicines for the treatment of a HIV infection)

   Prior or concomitant interferon therapy

   Yellow fever vaccine

   Live attenuated vaccines (except yellow fever)

   Ciclosporine, Tacrolimus

Pregnancy and breast-feeding

Hydroxycarbamide may impair the development of your unborn child. You must therefore not use hydroxycarbamide during pregnancy.

Women of childbearing potential should take contraceptive measures (for example: oral contraceptives - commonly known as the ‘Pill' and/or condoms) before starting and during treatment with hydroxycarbamide. If a patient intends to become pregnant after a therapy with hydroxycarbamide a specialized consultation is recommended.

If a doctor deems the use absolutely necessary during pregnancy, he/she should inform you about the possible risk for your child. If you become pregnant during treatment with hydroxycarbamide, inform your doctor without delay, and make use of the possibility of specialized counselling.

You must not use hydroxycarbamide while breast-feeding. If treatment is recommended by a doctor, you must stop breast-feeding.

Driving and using machines

Reactivity can be impaired during treatment with hydroxycarbamide. In this case, do not drive a car, and do not operate hazardous machines.


How to take Hydroxycarbamide


Treatment should be conducted only by experienced specialists.

Always take hydroxycarbamide exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

The capsules should be swallowed as a whole and must not disintegrate within the mouth.

The dosages stated in the following are based on the patient's actual or ideal weight, whichever is the less.

Your doctor determines the number of capsules and the duration of treatment.

Aggressive white blood cell disease

(chronic myeloid leukaemia)

Depending on the number of white blood cells, the initial dose is usually 40 mg hydroxycarbamide per kg bodyweight

daily.

Your doctor will reduce the dose to 20 mg per kg daily if the number of white blood cells falls below 20 x 109/l. The dose is then adjusted on an individual basis in order to keep the number of white blood cells at 5-10 x109/l.

If the white blood cells are less than 5 x 109 per litre, the dosage should be reduced, and it should be increased if they are above 10 x 109/l.

If the white blood cells fall below 2.5 x 109/l or the blood platelets below 100 x 109/l, your doctor should interrupt therapy until the values normalize.

An appropriate test time to determine the efficacy of hydroxycarbamide is 6 weeks. Your doctor will discontinue therapy if the disease is progressing. If there is a response, therapy can be continued indefinitely.


Continued on the next page >>


   Surplus of blood platelets

(essential thrombocythaemia)

For this disease, the initial dose is usually 15 mg hydroxycarbamide per kg bodyweight daily. This should keep the number of blood platelets below 600 x 109/l without reducing the number of white blood cells below 4 x 109/l.

   Surplus of certain blood cells

(polycythaemia vera)

In this case, treatment should be started with a dosage of 15-20 mg hydroxycarbamide per kg bodyweight

daily. The dose is to be adjusted on an individual basis in order to keep the ratio between red blood cells and blood plasma below 45% and the number of blood platelets below 400 x 109/l.

This can be achieved in most patients with a continuous administered dose of 1 to 2 hard capsules daily on average. If the ratio of red blood cells to blood plasma and the number of blood platelets remain stable, treatment should be continued indefinitely.

Children

As these diseases only rarely occur in children, no dosage schemes can be established at present.

Elderly patients

Elderly patients can have a more pronounced reaction to the effect of hydroxycarbamide and possibly require a lower dosage.

Patients with impaired liver or kidney function

Recommendations cannot be given for these patients as no data exists to date.

If you take more Hydroxycarbamide than you should

If the dosage taken was several times more than the recommended dosage, the following acute skin and/or mucosal changes may be signs of an overdose:

•    soreness

•    violet skin rash

•    swellings on palms and soles, followed by scaling of hands and feet

•    sore feet

•    excessive generalised pigmentation

•    severe inflammation of tissue which lines the mouth

Immediately inform a doctor if an overdose occurs. Immediate treatment consists of stomach irrigation, followed by supportive measures and monitoring of the blood formation.

If you forget to take Hydroxycarbamide

Do not take a double dose if you have forgotten the previous intake. Go back to your original directions for your next dose. If you are unsure contact your doctor.

If you stop taking Hydroxycarbamide

Your disease might worsen if therapy is discontinued.

Therapy with hydroxycarbamide may be terminated or interrupted only on the orders of the attending doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.


Rare, affects 1 to 10 users in 10,000

•    allergic reactions

•    hair loss

•    development of an acute lung reaction with accumulation of liquid in the lung, fever, shortness of breath

•    difficult or painful urination (dysuria)

•    Potentially life-threatening metabolic complications that can occur after treatment of cancer leading to increased uric acid level in the blood, which may result in gout or acute renal failure (tumour lysis syndrome)

Very rare, affects less than 1 user in 10,000 In isolated cases after maintenance therapy for several years with daily intake of hydroxycarbamide:

•    excessive pigmentation on skin and nails

•    thinning of skin and nails

•    ulcers of the lower legs

•    small, rough reddish patches on the skin, which may become skin cancer if not removed (actinic keratosis)

•    skin cancer

•    violet rash which is raised (small aggregation of cells)

•    skin scaling

•    impaired kidney function

•    skin ulcers (especially ulcers of the lower legs)

Another white blood cell cancer can develop in patients with excessive formation of blood cells and continuously treated with hydroxycarbamide. It is not known whether this is attributable to the underlying disease or to the treatment with hydroxycarbamide. The risk of an inflammation of the blood vessels of the skin, including blood vessel ulcerations and deterioration, is increased. Severe skin blood vessel ulcers have been reported in patients with myeloproliferative disease. Hydroxycarbamide should therefore be discontinued if such ulcerations develop. In addition, alternative medicines should be used if necessary.

Severe stomach complaints such as nausea, vomiting and loss of appetite, which can occur in combination with radiotherapy, can be controlled if administration of hydroxycarbamide is transiently stopped.

Hydroxycarbamide can enhance mucosal inflammations caused by radiation. Inflammatory reddening and excessive pigmentation can occur in pretreated tissue.

Inflammation of the blood vessels of the skin, including blood vessel ulcerations and deterioration, have occurred in patients with myeloproliferative disorders during therapy with hydroxycarbamide. This was reported most often in patients with a history of, or currently receiving, interferon therapy (see “Taking other medicines”).

High doses can cause moderate sleepiness.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.


How to store Hydroxycarbamide


4


Possible side effects


Like all medicines, hydroxycarbamide can cause side effects, although not everybody gets them.

Some side effects could be serious:

If any of the following happens, stop taking this medicine and tell your doctor immediately or go to the casualty department at your nearest hospital:

•    a severe allergic (hypersensitive) reaction Symptoms may include: allergic reaction in lung, reddening and swelling of the skin, itching

•    rare disorders of nerve function including headache, dizziness, disorientaion, hallucinations and fits

•    unusual bruising or bleeding caused by low blood platelets.


Keep out of the reach and sight of children.

Do not store above 30°C.

Do not use the medicine after the expiry date which is stated on the pack. The expiry date refers to the last day of that month.

The medicine should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.


6


Further information


What Hydroxycarbamide contains • The active substance is hydroxycarbamide

1 capsule, hard contains 500 mg hydroxycarbamide.


The strength of suppressed blood formation of the bone marrow determines the dosage or whether therapy must be interrupted in rare cases.

Side effects affecting the stomach or the intestine only rarely require dose reduction or cessation of treatment.

Side effects can occur with the following frequencies:

Common, affects 1 to 10 users in 100

•    suppressed blood formation in the bone marrow

•    reduced number of white blood cells (you are more prone to catch infections)

•    changes in the red blood count (megaloblastosis - large immature red blood cells).

Possible changes in the red blood count which do not respond to treatment with folic acid or vitamin B12 subside when therapy is discontinued.

•    diarrhoea

•    constipation

Uncommon, affects 1 to 10 users in 1,000

•    anaemia (reduction in red blood cells)

•    nausea, vomiting, loss of appetite

•    inflammation of tissue which lines the mouth

•    drug fever

•    chills

•    feeling unwell

•    flaky, knotty inflamed skin (rash or swollen patchy redness that changes the skin's texture), skin rash

•    inflammatory reddening affecting face, arms and legs

•    elevated liver enzymes

•    elevated bilirubin

•    transient disorders of tubular kidney function with increase in uric acid, urea and creatinine in blood


• The other ingredients are:

Capsule contents

Citric acid anhydrous, disodium hydrogen phosphate anhydrous, magnesium stearate

Capsule shell

Gelatin, ferric oxide, yellow, titanium dioxide

What Hydroxycarbamide looks like and contents of the pack

Capsule, hard with white lower part and yellow upper part

Hydroxycarbamide 500 mg capsules, hard are available in PVC/PVDC/aluminium-blister packs of 20, 25, 50, 100 and 120 capsules.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder Sandoz Ltd, WoolmerWay, Bordon, Hants, GU35 9QE, United Kingdom.

Manufacturer

AMAREG GmbH, Donaustaufer Str. 378, 93055 Regensburg, Germany

or

Salutas Pharma GmbH, Otto-von-Guericke-Allee 1,39179 Barleben, Germany.

This leaflet was last approved in 02/2010


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