Examples of using Hydroxycarbamide in English and their translations into German
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The extent of protein binding of hydroxycarbamide is unknown.
Hydroxycarbamide is unequivocally genotoxic in a wide range of test systems.
An erythema caused byradiation therapy may be aggravated by hydroxycarbamide.
In patients receiving long-term hydroxycarbamide for myeloproliferative disorders, secondary leukaemia has been reported.
Specific interaction studies have not been performed with hydroxycarbamide.
One of the mechanisms by which hydroxycarbamide acts is the elevation of foetal haemoglobin(HbF) concentrations in sickle cell patients.
Bone marrow depression is the dose-limiting toxic effect of hydroxycarbamide.
In nearly all clinicalstudies conducted in Sickle Cell Syndrome, hydroxycarbamide reduced the frequency of vaso-occlusive episodes by 66% to 80%, in children and in adults.
Skin cancer has also been reported in patients receiving long-term hydroxycarbamide.
Concurrent use of hydroxycarbamide and other myelosuppressive medicinal products or radiation therapy may increase bone marrow depression, gastro-intestinal disturbances or mucositis.
Haematological recovery usually occurs within two weeks of withdrawal of hydroxycarbamide.
Acute mucocutaneous toxicityhas been reported in patients receiving hydroxycarbamide at doses several times above the therapeutic dose.
Leg ulcers are a common complication of Sickle Cell Syndrome,but have also been reported in patients treated with hydroxycarbamide.
Hydroxycarbamide distributes rapidly throughout the human body, enters the cerebrospinal fluid, appears in peritoneal fluid and ascites, and concentrates in leukocytes and erythrocytes.
In all clinical studies, there was a significant increase in HbF from baseline after hydroxycarbamide use.
Specifically the safety of hydroxycarbamide had been examined retroactively from cohorts of 123 adults over 13 years and 352 children older than 2 years and adolescents up to 12 years.
Cutaneous vasculitic toxicities, including vasculitic ulcerations and gangrene, have occurred in patients with myeloproliferative disorders during therapy with hydroxycarbamide.
Hydroxycarbamide crosses the placenta barrier and has been demonstrated to be a potent teratogen and embryotoxic in a wide variety of animal models at or below the human therapeutic dose.
During treatment with Siklos, blood counts must be monitored every two weeks at treatment initiation(i. e. for the first two months)and if the daily dose of hydroxycarbamide is up to 35 mg/ kg b.
At concentrations ranging from 10 to 300 µM, hydroxycarbamide does not stimulate the in vitro ATPase activity of recombinant human P glycoprotein(PGP), indicating that hydroxycarbamide is not a PGP substrate.
Potentially fatal pancreatitis and hepatotoxicity, and severe peripheral neuropathy havebeen reported in HIV-infected patients who received hydroxycarbamide in combination with antiretroviral agents particularly didanosine plus stavudine.
Because hydroxycarbamide is a well-known substance that is already used in other medicines, the company used data from the scientific literature to support the use of Siklos in adults and children with sickle cell syndrome.
Due to potentially severe clinical outcomes for the cutaneous vasculiticulcers reported in patients with myeloproliferative disease, hydroxycarbamide should be discontinued and/ or its dose reduced if cutaneous vasculitic ulcerations develop.
The active substance of Siklos, i. e. hydroxycarbamide, is a substance which inhibits growth and proliferation of some cells, such as blood cells; these effects lead to a reduction of circulating red, white and coagulation blood cells myelosuppressive effect.
Patients with normal(creatinine clearance CrCl> 80 ml/ min), mild(CrCl 60- 80 ml/ min), moderate(CrCl 30-< 60 ml/ min), or severe(< 30 ml/ min)renal impairment received hydroxycarbamide as a single dose of 15 mg/ kg b. w. by using 200 mg, 300 mg, or 400 mg capsules.
Recently, hydroxycarbamide has shown to be associated with the generation of nitric oxide suggesting that nitric oxide stimulates cyclic guanosine monophosphatase(cGMP) production, which then activates a protein kinase and increases the production of HbF.
On the basis of the scientific conclusions for Siklos, the CHMP is of the opinion that the benefit-risk balance of the medicinal product containing the active substance HYDROXYCARBAMIDE is favourable subject to the proposed changes to the product information.
Hydroxycarbamide administered to male rats at 60 mg/kg b. w./day(about double the recommended usual maximum dose in humans) produced testicular atrophy, decreased spermatogenesis and significantly reduced their ability to impregnate females.
As evaluated in a further study, in patients with a CrCl< 60 ml/ min the area under the curve was approximately 51% higher than in patients with a CrCl≥ 60 ml/ min,which suggests that a dose reduction of hydroxycarbamide by 50% may be appropriate in patients with a CrCl< 60 ml/ min.
Other known pharmacological effects of hydroxycarbamide which may contribute to its beneficial effects in Sickle Cell Syndrome include decrease of neutrophils, increase of the water content of erythrocytes, increase of the deformability of sickled cells, and altered adhesion of red blood cells to the endothelium.
