Hydroxycarbamide

  • N- hydroxyurea
  • Hydroxyurea
  • Hydroxyurea

L01XX05

White solid

Cytostatic

Ribonucleotide reductase inhibitor

144-146 ° C

Soluble in water

Risk

Template: Infobox chemical / molecular formula search available

Hydroxyurea ( INN), also hydroxyurea and Hydroxurea, is an antineoplastic agent used to treat particularly of malignant blood diseases ( leukemia, myeloproliferative diseases) is used. It also finds use in the treatment of sickle cell anemia and in the context of antiretroviral treatment in HIV infection.

Mechanism of action

The effect of the substance based on inhibition of the enzyme ribonucleotide reductase which DNA synthesis capacity of each cell is significantly reduced.

Pharmacokinetics

Following oral administration of hydroxyurea is rapidly absorbed from the gastrointestinal tract. The exact bioavailability is not known, but appears to be high (no significant difference in the levels with oral versus iv administration ). The maximum serum concentration is reached about 2 hours after ingestion. Given the small size of the molecule diffuses well into various body compartments hydroxyurea. At higher blood levels and the blood- brain barrier is overcome and there is a crossing into the cerebrospinal fluid. The substance penetrates into ascites, pleural effusions and in breast milk. The mechanism of biotransformation or metabolism is not known. Metabolised via the cytochrome P450 system does not occur. The substance is excreted unchanged primarily through the kidneys.

Medical Application

In myeloproliferative disorders

Hydroxyurea applies to cytoreductive therapy in myeloproliferative disorders ( chronic myeloid leukemia ( CML), polycythemia vera, Essential thrombocythemia myelofibrosis ). The use in CML has declined sharply after the introduction of imatinib ( Gleevec ®), but in certain situations, the use of hydroxyurea may also be useful. In polycythemia vera usually the regular phlebotomy is the treatment of choice, with significantly elevated white blood cell counts or platelet counts, however, the use of hydroxyurea may be useful. A classic application is the Essential thrombocythemia, here the substance competes with the drug anagrelide. The myelofibrosis is also a typical application.

Sickle cell anemia

By the European Medicines Agency EMA, the substance was also approved for the treatment of sickle cell anemia. On 29 June 2007 the company Addmedica (Paris) received approval for the marketing of hydroxyurea ( Siklos ®) for this indication. In patients with sickle cell anemia may sometimes occur life-threatening or painful vaso -occlusive crises, ie Vascular occlusion by Zusammenklumpung of sickle cells. Has been shown in several clinical studies have shown that mild antiproliferative active substances in the prevention of vaso -occlusive crises such may be effective.

Antiretroviral therapy for HIV infection

A number of clinical studies have investigated the combination of hydroxyurea with antiretroviral agents for the treatment of HIV infection. It showed inconsistent results. An application should therefore be made only within controlled clinical trials. An authorization for the treatment of HIV infection has not the substance.

Off- label use

Notes on the use of hydroxyurea in chronic myelomonocytic leukemia ( CMML ) according to § 30, paragraph 2 AM- RL.

Dosage

The substance is dispensed in tablets of 500 or 1000 milligrams ( mg). The usual dose is between 250 mg per day ( eg, a Tbl of 500 mg every 2 days) to about 2 g daily.

Side effects

Possible side effects include: drowsiness, nausea, vomiting (rare), diarrhea, constipation, stomatitis (rare), loss of appetite, hair loss, skin rash, liver appreciation ( usually temporarily). Medically significant side effect is cushioning effect not only on the blood disease, but also to the healthy hematopoiesis ( myelosuppression ). These effects usually limit the dose that can be given. An important side effect is the increase in uric acid in the blood. In certain predisposed patients, this may result in deterioration of renal function or even gout. Whether hydroxycarbamide has a leukemogenic potential, ie whether a treatment is an increased risk of developing later from leukemia, is controversial. Probably it must be a low risk. It has also been reported isolated cases of patients with squamous ( squamous cell carcinoma of the skin) after hydroxyurea therapy.

Use in pregnancy

Hydroxyurea is in animal experiments unequivocally genotoxic and embryotoxic. Women who are planning a pregnancy, hydroxyurea should stop after consultation with the attending physician.

Trade names

Litalir (D, A, CH), Siklos (A), Syrea (D),

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