The treatment of chronic myeloid leukaemia.

The treatment of cancer of the cervix in conjunction with radiotherapy.

Posology

Adults

Treatment regimens can be continuous or intermittent. The continuous regimen is particularly suitable for chronic myeloid leukaemia, while the intermittent regimen, with its diminished effect on the bone marrow, is more satisfactory for the management of cancer of the cervix.

Cekea should be started 7 days before concurrent irradiation therapy. If Cekea is used concomitantly with radiotherapy, adjustment of radiation dosage is not usually necessary.

An adequate trial period for determining the antineoplastic effect of Cekea is six weeks. Where there is a significant clinical response therapy may be continued indefinitely, provided that the patient is kept under adequate observation and shows no unusual or severe reactions. Therapy should be interrupted if the white cell count drops below 2.5x10⁹ L or the platelet count below 100x10 ⁹/L (see section 4.4).

In these cases, the counts should be reevaluated after three days and therapy resumed when the counts return to acceptable levels. Hematopoietic rebound is usually rapid. If rapid rebound has not occurred during combined Cekea and irradiation therapy, irradiation may also be interrupted. Anemia, even if severe, can be managed without interrupting Cekea therapy.

Severe gastric distress, such as nausea, vomiting, and anorexia, resulting from combined therapy may usually be controlled by interruption of Cekea administration.

Pain or discomfort from inflammation of the mucous membranes at the irradiated site (mucositis) is usually controlled by measures such as topical anesthetics and orally administered analgesics. If the reaction is severe, Cekea therapy maybe temporarily interrupted; if it is extremely severe, irradiation dosage may, in addition, be temporarily postponed.

Continuous therapy

Cekea 20-30 mg/kg should be given daily in single doses. Dosage should be based on the patient's actual or ideal weight, whichever is the less. Therapy should be monitored by repeat blood counts.

Intermittent therapy

Cekea 80 mg/kg in single doses should be given every third day. Using the intermittent regimes the likelihood of WBC depression is diminished, but if low counts are produced, 1 or more doses of Cekea should be omitted.

Concurrent use of Cekea with other myelosuppressive agents may require adjustments of dosages.

Special Populations

Children

Because of the rarity of these conditions in children, dosage regimens have not been established.

Elderly

Elderly patients may be more sensitive to the effects of hydroxycarbamide (hydroxyurea), and may require a lower dosage regimen.

Renal Impairment

Since renal excretion is a pathway of elimination, consideration should be given to decreasing the dosage of Cekea in this population.

Method of administration

For oral use.

NB: If the patient prefers, or is unable to swallow capsules, the contents of the capsules may be emptied into a glass of water and taken immediately. The contents of capsules should not be inhaled or allowed to come into contact with the skin or mucous membranes. Spillages must be wiped immediately.

Bone Marrow

The complete status of the blood, including bone marrow examination, if indicated, as well as kidney function and liver function should be determined prior to, and repeatedly during, treatment. If bone marrow function is depressed, treatment with Cekea 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 (hydroxyurea) 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.

Cekea may produce bone marrow suppression; leukopenia is generally its first and most common manifestation. Thrombocytopenia and anaemia occur less often and are seldom seen without a preceding leukopenia. Bone marrow depression is more likely in patients who have previously received radiotherapy or cytotoxic cancer chemotherapeutic agents; Cekea should be used cautiously in such patients. The recovery from myelosuppression is rapid when Cekea therapy is interrupted.

Anaemia

Severe anaemia must be corrected with whole blood replacement before initiating therapy with hydroxycarbamide (hydroxyurea). If, during treatment, anaemia occurs, correct without interrupting Cekea therapy. Erythrocytic abnormalities; megaloblastic erythropoeisis, which is self-limiting, is often seen early in the course of hydroxycarbamide (hydroxyurea) therapy. The morphologic change resembles pernicious anaemia, but is not related to vitamin B12 or folic acid deficiency. The macrocytosis may mask the incidental development of folic acid deficiency; regular determinations of serum folic acid are recommended. Hydroxycarbamide (hydroxyurea) 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.

Irradiation

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

Renal

Hydroxycarbamide (hydroxyurea) should be used with caution in patients with marked renal dysfunction.

HIV

Hydroxycarbamide (hydroxyurea) is not licensed for use in combination with antiretroviral agents for HIV disease and it may cause treatment failure and toxicities (in some cases fatal) in HIV patients (see section 4.5).

Cancer

In patients receiving long-term therapy with hydroxycarbamide (hydroxyurea) for myeloproliferative disorders, such as polycythemia vera and thrombocythemia, secondary leukaemia has been reported. It is unknown whether this leukaemogenic effect is secondary to hydroxycarbamide (hydroxyurea) or associated with the patient's underlying disease. Skin cancer has also been reported in patients receiving long-term hydroxycarbamide (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.

Vasculitis toxicities

Cutaneous vasculitic toxicities including vasculitic ulcerations and gangrene have occurred in patients with myeloproliferative disorders during therapy with hydroxycarbamide (hydroxyurea). The risk of vasculitic toxicities is increased in patients who receive prior or concomitant interferon therapy. The digital distribution of these vasculitic ulcerations and progressive clinical behaviour of peripheral vasculitic insufficiency leading to digital infarct or gangrene were distinctly different than the typical skin ulcers generally described with Hydroxycarbamide (hydroxyurea). Due to potentially severe clinical outcomes for the cutaneous vasculitic ulcers reported in patients with myeloproliferative disease, hydroxycarbamide (hydroxyurea) should be discontinued if cutaneous vasculitic ulcerations develop and alternative cytoreductive agents should be initiated as indicated.

Uric acid

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 (hydroxyurea), 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.

Lactose

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.[MA1] 

Vaccinations

Concomitant use of Cekea with a live virus vaccine may potentiate the replication of the vaccine virus and/or may increase some of the adverse reactions of the vaccine virus because normal defence mechanisms may be suppressed by hydroxycarbamide (hydroxyurea). Vaccination with a live vaccine in a patient taking Cekea may result in severe infection. The patient's antibody response to vaccines may be decreased. The use of live vaccines should be avoided during treatment and for at least six months after treatment has finished and individual specialist advice sought (see section 4.5).

 [MA1]This information is in the brand, Please make sure that our product contains the same excipient or otherwise please remove it

The myelosuppressive activity may be potentiated by previous or concomitant radiotherapy or cytotoxic therapy. Fatal and non-fatal pancreatitis has occurred in HIV-infected patients during therapy with hydroxycarbamide (hydroxyurea) and didanosine, with or without stavudine. Hepatotoxicity and hepatic failure resulting in death were reported during post-marketing surveillance in HIV-infected patients treated with hydroxycarbamide (hydroxyurea) and other antiretroviral agents. Fatal hepatic events were reported most often in patients treated with the combination of hydroxycarbamide (hydroxyurea), didanosine and stavudine. This combination should be avoided. Peripheral neuropathy, which was severe in some cases, has been reported in HIV-infected patients receiving hydroxycarbamide (hydroxyurea) in combination with antiretroviral agents, including didanosine, with or without stavudine. (see section 4.4).

Studies have shown that there is an analytical interference of hydroxycarbamide (hydroxyurea) 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 (hydroxyurea).

Vaccinations

There is an increased risk of severe or fatal infections with the concomitant use of live vaccines. Live vaccines are not recommended in immunosuppressed patients (see section 4.4).

Drugs which affect DNA synthesis, such as hydroxycarbamide (hydroxyurea), may be potent mutagenic agents. The physician should carefully consider this possibility before administering this drug to male or female patients who may contemplate conception. Since Cekea is a cytotoxic agent it has produced a teratogenic effect in some animal species.

In rats and dogs, high doses of hydroxycarbamide (hydroxyurea) reduced sperm production

Hydroxycarbamide (hydroxyurea) is excreted in human breast milk. Because of the potential for serious adverse reactions in nursing infants from hydroxycarbamide (hydroxyurea), a decision should be made whether to discontinue nursing or to discontinue Cekea, taking into account the importance of the drug to the mother.

Cekea can cause fetal harm when administered to a pregnant woman. Cekea 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.

Female patients of reproductive potential should be counselled to use effective contraception during therapy and for at least 6 months after therapy.

Azoo- or oligospermia, sometimes reversible, have been observed in men. Male patient should be informed about the possibility of sperm conservation before the start of therapy. Hydroxycarbamide (hydroxyurea) may be genotoxic.

Men under therapy are advised to use effective contraceptive measures during and at least 1 year after therapy.

Hydroxycarbamide (hydroxyurea) may cause drowsiness. Patients receiving it should not drive or operate machinery unless it has been shown not to affect physical or mental ability.

Bone-marrow suppression is the major toxic effect of hydroxycarbamide (hydroxyurea)

Cutaneous vasculitic toxicities including vasculitic ulcerations and gangrene have occurred in patients with myeloproliferative disorders during therapy with hydroxycarbamide (hydroxyurea). The risk of vasculitic toxicities is increased in patients who receive prior or concomitant interferon therapy.

In some patients, hyperpigmentation, nail pigmentation, atrophy of skin and nails, scaling, violet papules and alopecia have been observed following several years of long-term daily maintenance therapy with hydroxycarbamide (hydroxyurea).

Cases of fatal and non-fatal pancreatitis and hepatotoxicity and severe peripheral neuropathy have been observed in HIV patients when hydroxycarbamide (hydroxyurea) was administered with antiretroviral agents, in particular didanosine plus stavudine. Patients treated with hydroxycarbamide (hydroxyurea) in combination with didanosine, stavudine and indinavir showed a median decline in CD4 cells of approximately 100/mm³ (see sections 4.4 and 4.5).

Adverse reactions observed with combined hydroxycarbamide (hydroxyurea) and irradiation therapy were similar to those reported with the use of hydroxycarbamide (hydroxyurea) alone, primarily bone marrow depression (leukopenia and anaemia) and gastric irritation. Nearly all patients receiving an adequate course of combined hydroxycarbamide (hydroxyurea) and irradiation therapy will develop leukopenia. Decreased platelet counts (<100,000/mm³) have occurred rarely and usually in the presence of marked leukopenia. Hydroxycarbamide (hydroxyurea) may potentiate some adverse reactions usually seen with irradiation alone, such as gastric distress and mucositis.

Hypersensitivity

Drug induced fever

High fever (>39°C) requiring hospitalisation in some cases has been reported concurrently with gastrointestinal, pulmonary, muscloskeletal, hepatobiliary, dermatoloigical or cardiovascular manifestations. Onset typically occurred within 6 weeks of initiation and resolved promptly after discontinuation of hydroxycarbamide (hydroxyurea). Upon readministration fever re-occurred within 24 hours.

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).

To reports any side effect(s):

Saudi Arabia:

Other GCC States:

Immediate treatment consists of gastric lavage, followed by supportive therapy for the cardiorespiratory systems if required. In the long term, careful monitoring of the haemopoietic system is essential and, if necessary, blood should be transfused.

Acute mucocutaneous toxicity has been reported in patients receiving hydroxycarbamide (hydroxyurea) at a dosage several times greater than that recommended. Soreness, violet erythema, oedema on palms and foot soles followed by scaling of hands and feet, intense generalised hyperpigmentation of skin, and severe acute stomatitis were observed.

Pharmacotherapeutic group: other antineoplastic agents

ATC Code: L01XX05

Hydroxycarbamide (hydroxyurea) is an orally active antineoplastic agent. Although the mechanism of action has not yet been clearly defined, hydroxycarbamide (hydroxyurea) appears to act by interfering with synthesis of DNA.

After oral administration hydroxycarbamide (hydroxyurea) is readily absorbed from the gastrointestinal tract. Peak plasma- concentrations are reached in 2 hours; by 24 hours the serum concentrations are virtually zero. Approximately 80% of an oral or intravenous dose of 7 to 30 mg/kg may be recovered from the urine within 12 hours. Hydroxycarbamide (hydroxyurea) crosses the blood-brain barrier. Hydroxycarbamide (hydroxyurea) is well distributed throughout the body.

Hydroxycarbamide (hydroxyurea) is unequivocally genotoxic and a presumed transpecies carcinogen which implies a carcinogenic risk to humans.

Lactose Monohydrate

Disodium Phosphate Anhydrous

Citric Acid

Colloidal Silicon Dioxide

Magnesium Stearate

Not applicable

Do not store above 30°C

Cekea Capsules 200 mg:

White to off-white colored powder filled in size ‘3’ hard gelatin capsules with Dark green colored cap imprinted ‘SPC-08’ with white ink and Dark green colored body imprinted ’200 mg’ with white ink.

Cekea Capsules 500 mg:

White to off-white colored powder filled in size ‘0’ hard gelatin capsules with opaque light green colored cap imprinted ‘SPC-07’ with black ink and opaque pink colored body imprinted ‘500 mg’

Cekea capsules are packed in blister. 10 caps/blister. Pack size is 3 blister/ Carton.

People who are not taking Cekea should not be exposed to it. To decrease the risk of exposure, wear disposable gloves when handling Cekea. Anyone handling Cekea should wash their hands before and after contact with the capsules. If the powder is spilled, it should be immediately wiped with a damp disposable towel and discarded in a closed container, such as a plastic bag, as should the empty capsules.

Cekea should be kept away from children. Pregnant women should not handle Cekea.

To minimise the risk of dermal exposure, always wear impervious gloves when handling capsules containing Cekea. This includes all handling activities in clinical settings, pharmacies, storerooms and home healthcare settings, including during unpacking and inspection, transport within a facility, and dose preparation and administration.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.