Mylostat Capsule

Hydroxyurea is converted to a free radical nitroxide (NO) in vivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme. The entire replicase complex, including ribonucleotide reductase, is inactivated and DNA synthesis is selectively inhibited, producing cell death in S phase and synchronization of the fraction of cells that survive. Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea, offering potential synergy between hydroxyurea and radiation or alkylating agents. Hydroxyurea also increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises in sickle cell anemia. Levels of fetal hemoglobin increase in response to activation of soluble guanylyl cyclase (sGC) by hydroxyurea-derived NO.

To minimize the risk of dermal exposure, always wear impervious gloves when handling Hydroxyurea capsules. Hydroxyurea capsules should not be opened. Personnel should avoid exposure to crushed or opened capsules. If contact with crushed or opened capsules occurs, wash immediately and thoroughly. More information is available in the references listed below. Because of the rarity of melanoma, resistant chronic myelocytic leukemia, carcinoma of the ovary and carcinomas of the head and neck in pediatric patients, dosage regimens have not been established. All dosage should be based on the patient's actual or ideal weight, whichever is less. Concurrent use of Hydroxyurea with other myelosuppressive agents may require adjustment of dosages. Since Hydroxyurea may raise the serum uric acid level, dosage adjustment of uricosuric medication may be necessary.

Solid Tumors: Intermittent Therapy: 80 mg/kg administered orally as a single dose every third day.

Continuous Therapy: 20 to 30 mg/kg administered orally as a single dose daily.

Concomitant Therapy with Irradiation: Carcinoma of the head and neck-80 mg/kg administered orally as a single dose every third day. Administration of Hydroxyurea should begin at least seven days before initiation of irradiation and continued during radiotherapy as well as indefinitely afterwards provided that the patient may be kept under adequate observation and evidences no unusual or severe reactions. Irradiation should be given at the maximum dose considered appropriate for the particular therapeutic situation; adjustment of irradiation dosage is not usually necessary when Hydroxyurea is used concomitantly.

Resistant Chronic Myelocytic Leukemia: Until the intermittent therapy regimen has been evaluated, Continuous Therapy 20-30 mg/kg administered orally as a single dose daily is recommended.

Polycythemia Vera: Dosage regimens for the treatment of p. vera may be initiated at 30mg/kg for one week, followed by 15-20mg/kg daily.

Essential Thrombocythemia: Initial dose of hydroxyurea is about 15mg/kg per day. Doses are subsequently adjusted according to platelet counts.

Sickle-cell disease: The initial dose of Hydroxyurea is 15 mg/kg/day as a single dose. 

β-thalassemia patients: 15-30 mg/kg administered orally as a single dose daily

Increased toxicity such as pancreatitis, hepatotoxicity, peripheral neuropathy with concomitant use of antiretroviral drugs. There is an analytical interference of Mylostat with the enzymes (urease, uricase and lactate dehydrogenase) used in the determination of urea, uric acid and lactic acid.

It is contraindicated in patients with known hypersensitivity to hydroxyurea or any other components of this formulation.

The most common side effects are headache, myelosuppression, skin diseases, fever, chills.

Pregnancy category D. There are no adequate and well-controlled studies in pregnant women. There are potential risk to fetus and women should avoid becoming pregnant while being treated with hydroxyurea. It is excreted in human milk. Because of the potential for serious adverse reactions in a breastfed infant from hydroxyurea, including carcinogenicity, patients should be discontinue breastfeeding during treatment with hydroxyurea.

Mylostat causes severe myelosuppression. Treatment with Mylostat should not be initiated if bone marrow function is markedly depressed. Renal and hepatic function should be monitored before and during treatment. Full blood count is needed before treatment and repeatedly throughout use. Patients receiving long-term therapy for malignant disease should be monitored for secondary malignancies.

Acute mucocutaneous toxicity has been reported in patients receiving Mylostat at dosages several times the therapeutic dose. Soreness, violet erythema, edema on palms and soles followed by scaling of hands and feet, severe generalized hyperpigmentation of the skin, and stomatitis have also been observed.

Cytotoxic Chemotherapy

Store at 25°C in a dry place.