Updated section 4.8 of the SmPC and with consequential changes to the section 4 of the package leaflet in line with the outcome of a PRAC signal recommendation.

 

Type II variation to update various sections of the SmPC in line with Company Core Data Sheet (CCDS) dated March 2014.

1. NAME OF THE MEDICINAL PRODUCT

s contains 500 mg of Hydroxycarbamide.

Excipients

with known effect: Contains Lactose Monohydrate 42.2 mg

For

a the full list of excipients, see Section section 6.1.

s hard.

Size 0 hard gelatin capsule with an opaque pink body and an opaque green cap, containing a white homogeneous powder. Printed with 'BMS 303' in black ink.

9/L or the platelet count below 100x109/L (see section 4.4).

9/L), thrombocytopenia (<100x109/L), or severe anaemia and previously shown hypersensitivity to Hydrea. Use in non-malignant disease.

If bone marrow function is depressed, treatment with Hydrea should not be initiated. The determination of haemoglobin level, total leukocyte counts, and platelet counts should be performed at least once a week throughout the course of hydroxycarbamide therapy. If WBC falls below 2.5x109/L or Platelet count to <100x109/L, therapy should be interrupted. Counts should be rechecked after 3 days and treatment resumed when they rise significantly towards normal.

12 or folic acid deficiency. The macrocytosis may mask the incidental development of folic acid deficiency; thus, prophylactic administration of folic acid may be warranted. Hydroxycarbamide may also delay plasma iron clearance and reduce the rate of iron utilisation by erythrocytes but it does not appear to alter the red blood cell survival time.

hydroxycarbamidehydroxyurea for myeloproliferative disorders, such as polycythemia vera and thrombocythemia, secondary leukemia has been reported; it is unknown whether this leukemogenic effect is secondary to hydroxycarbamidehydroxyurea or the patient’s underlying disease. Skin cancer has also been reported in patients receiving long-term hydroxyurea. Patients should be advised to protect skin from sun exposure, conduct self-inspection of the skin and be screened for secondary malignancies during routine follow-up visits.

This product contains lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

This combination should be avoided. Patients treated with hydroxycarbamide in combination with didanosine, stavudine, and indinavir in study ACTG 5025 showed a median decline in CD4 cells of approximately 100/mm³.

Studies have shown that there is an analytical interference of hydroxycarbamide with the enzymes (urease, uricase, and lactic dehydrogenase) used in the determination of urea, uric acid and lactic acid, rendering falsely elevated results of these in patients treated with hydroxycarbamide.

Because of the potential for serious adverse reactions in nursing infants from hydroxyurea, a decision should be made whether to discontinue nursing or to discontinue Hydrea, taking into account the importance of the drug to the mother.

Hydrea can cause fetal harm when administered to a pregnant woman. This productHydrea

should not normally be administered to patients who are pregnant, or to mothers who are breast feeding, unless the potential benefits outweigh the possible hazards.

When appropriate both male and female patients should be counselled concerning the use of contraceptive measures before and during treatment with Hydrea.

s contains 500 mg of Hydroxycarbamide.

Excipients

with known effect: Contains Lactose Monohydrate 42.2 mg

For

a the full list of excipients, see Section section 6.1.

9/L or the platelet count below 100x109/L (see section 4.4).

9/L), thrombocytopenia (<100x109/L), or severe anaemia and previously shown hypersensitivity to Hydrea. Use in non-malignant disease.

If bone marrow function is depressed, treatment with Hydrea should not be initiated. The determination of haemoglobin level, total leukocyte counts, and platelet counts should be performed at least once a week throughout the course of hydroxycarbamide therapy. If WBC falls below 2.5x109/L or Platelet count to <100x109/L, therapy should be interrupted. Counts should be rechecked after 3 days and treatment resumed when they rise significantly towards normal.

Severe anaemia must be corrected with whole blood replacement before initiating therapy with hydroxycarbamide. If, during treatment, anaemia occurs, correct without interrupting Hydrea therapy. Erythrocytic abnormalities; megaloblastic erythropoeisis, which is self-limiting, is often seen early in the course of hydroxycarbamide therapy. The morphologic change resembles pernicious anaemia, but is not related to Vitamin B

12 or folic acid deficiency. The macrocytosis may mask the incidental development of folic acid deficiency; thus, prophylactic administration of folic acid may be warranted. Hydroxycarbamide may also delay plasma iron clearance and reduce the rate of iron utilisation by erythrocytes but it does not appear to alter the red blood cell survival time.

Patients who have received irradiation therapy in the past may have an exacerbation of postirradiation erythema when Hydrea is given.

The possibility of an increase in serum uric acid, resulting in the development of gout or, at worst, uric acid nephropathy, should be borne in mind in patients treated with hydroxycarbamide, especially when used with other cytotoxic agents. It is therefore important to monitor uric acid levels regularly and maintain a high fluid intake during treatment.

In patients receiving long-term therapy with hydroxycarbamide for myeloproliferative disorders, such as polycythemia, secondary leukaemia has been reported. It is unknown whether this leukaemogenic effect is secondary to hydroxycarbamide or associated with the patients' underlying disease.

Cutaneous vasculitic toxicities including vasculitic ulcerations and gangrene have occurred in patients with myeloproliferative disorders during therapy with hydroxycarbamide. These vasculitic toxicities were reported most often in patients with a history of or currently receiving interferon therapy. Due to potentially severe clinical outcomes for the cutaneous vasculitic ulcers reported in patients with myeloproliferative disease, hydroxycarbamide should be discontinued if cutaneous vasculitic ulcerations develop and alternative cytoreductive agents should be initiated as indicated.

Hydroxycarbamide has been shown to be carcinogenic in animals. The possibility of a similar effect should be borne in mind when designing the long-term management of the patient.

In patients receiving long-term

hydroxycarbamidehydroxyurea for myeloproliferative disorders, such as polycythemia vera and thrombocythemia, secondary leukemia has been reported; it is unknown whether this leukemogenic effect is secondary to hydroxycarbamidehydroxyurea or the patient’s underlying disease. Skin cancer has also been reported in patients receiving long-term hydroxyurea. Patients should be advised to protect skin from sun exposure, conduct self-inspection of the skin and be screened for secondary malignancies during routine follow-up visits.

This combination should be avoided. Patients treated with hydroxycarbamide in combination with didanosine, stavudine, and indinavir in study ACTG 5025 showed a median decline in CD4 cells of approximately 100/mm³.

Studies have shown that there is an analytical interference of hydroxycarbamide with the enzymes (urease, uricase, and lactic dehydrogenase) used in the determination of urea, uric acid and lactic acid, rendering falsely elevated results of these in patients treated with hydroxycarbamide.

Because of the potential for serious adverse reactions in nursing infants from hydroxyurea, a decision should be made whether to discontinue nursing or to discontinue Hydrea, taking into account the importance of the drug to the mother.

Hydrea can cause fetal harm when administered to a pregnant woman. This productHydrea

should not normally be administered to patients who are pregnant, or to mothers who are breast feeding, unless the potential benefits outweigh the possible hazards.

When appropriate both male and female patients should be counselled concerning the use of contraceptive measures before and during treatment with Hydrea.

hydroxycarbamideHydrea, while leucopenia, thrombocytopenia and anaemia may occur in that order.

Other side-effects are generally rare, but the following have been reported.

Respiratory disorders

Pulmonary oedema

Acute pulmonary reactions consisting of diffuse pulmonary infiltrates/fibrosis, and dyspnoea have been rarely reported.

Vascular disorders

The risk of vasculitic toxicities is increased in patients who receive prior or concomitant interferon therapy.These vasculitic toxicities were reported most often in patients with a history of or currently receiving interferon therapy.

Gastrointestinal disorders

Nausea, vomiting, diarrhoea, constipation, melaena, abdominal pain, stomatitis

Genitourinary disorders

Dysuria and impairment of renal tubular function accompanied by elevation in serum

uric acid, BUN, and creatinine levels.

Skin and epithelial disorders

Alopecia, skin rash, skin ulceration, skin cancer has also been rarely reported

.

3 (see sections 4.4 and 4.5).

3) have occurred rarely and usually in the presence of marked leukopenia. Hydrea may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis.

The list is presented by system organ class, MedDRA preferred term, and frequency using the following frequency categories: very common (

≥1/10), common (≥1/100,

< 1/10), uncommon (

≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (< 1/10000), and not known (cannot be estimated from the available data).

The following text has been added to section 4.4 and 4.5 of the SmPC:

Section 4.4:

In patients receiving long-term hydroxyurea for myeloproliferative disorders, such as
polycythemia vera and thrombocythemia, secondary leukemia has been reported; it is

unknown whether this leukemogenic effect is secondary to hydroxyurea or the

patient’s underlying disease. Skin cancer has also been reported in patients receiving

long-term hydroxyurea. Patients should be advised to protect skin from sun exposure,

conduct self-inspection of the skin and be screened for secondary malignancies during

routine follow-up visits.

Section 4.5: 
 

Studies have shown that there is an analytical interference of hydroxycarbamide with the enzymes (urease, uricase, and lactic dehydrogenase)

used in the determination of urea, uric acid and lactic acid, rendering falsely elevated results of these in patients treated with hydroxycarbamide.

Sections 1, 2, 3, 6.1, 6.4, 6.6 - revised in line with SPC QRD Template

 Section 6.3 - Reduction of shelf life from 5 to 2 years. 

Sections 9 and 10 - Dates of renewal and revision