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| >> Clinical Guidelines Hydroxycarbamide (Previously known as Hydroxyuera)
Hydroxycarbamide is a second line modality for the treatment of psoriasis and has been used since 1965. It is usually reserved for cases where other second line agents have failed or are contraindicated. The dose used has generally been 0.5 to 2.0g daily, give orally either as a single dose, or divided into two doses (morning and evening). Although only a single controlled trial has been performed, it is generally considered to be effective. Hydroxycarbamide avoids the hepatotoxicity associated with methotrexate, and the nephrotoxicity associated with ciclosporin, and can therefore often be useful when other drugs are contraindicated, although it should be avoided, if possible, when renal function is markedly impaired. The main hazard is myelosuppression and careful monitoring of the full blood count is therefore required. It is recommended that the initial dose in adults should usually be 1g daily and this can be titrated, according to efficacy and toxicity, up to a maximum of 2g daily. Full blood count, including platelet and differential white cell counts, should be performed at least weekly for the first two months. Efficacy
The use of hydroxycarbamide in the treatment of psoriasis has been confirmed in a double-blind, placebo controlled crossover trial. Each treatment period was 4 weeks, and the dose of hydroxycarbamide was 0.5g twice daily. Twelve subjects were included and 10 completed the protocol. Subjects and investigators considered that improvement had occurred during active therapy in 9 and 7 out of 10 cases respectively. Only one patient improved by either assessment during placebo treatment. The level of response was not quantified and no statistical analysis was presented. Moschella and Greenwald reported a study in which 60 patients were treated intermittently with hydroxyurea (hydroxycarbamide), starting at the dose of 500mg twice daily. Patients who failed to respond to the initial dose were treated with 1.5g daily. During the first 6 weeks of treatment, 63% of the patients showed a good or excellent response, including some with erythrodermic and pustular psoriasis; a fair response was seen in another 10%. Patients in whom the drug was effective generally began to show some improvement within 2 to 3 weeks. In the majority of these patients the response was able to be successfully maintained by subsequent courses of treatment. Layton et al. reported their experience of treating 85 patients, at doses of 0.5 -1.5g daily, over a period of eight years. Sixty percent of these patients cleared completely or nearly completely, and a further 20% showed partial clearance. The response was maintained in 52 by continuous therapy, for a mean of 16 months at the time of reporting. The reported duration of remission following cessation of hydroxycarbamide has varied from 24 hours to several months. Rebound of psoriasis after discontinuation has been occasionally reported. Hydroxycarbamide has sometimes been helpful in treating generalised pustular psoriasis but results are variable. Synergy with other treatments
Hydroxycarbamide has been used safely and effectively in combination with ciclosporin, more caution is necessary in combination with other potentially myelosuppressive drugs Safety, side-effects and patient acceptability
The main concern regarding toxicity of hydroxycarbamide has been over myelosuppression, which may manifest as megaloblastic anaemia, thrombocytopenia or leukopenia. Haematological abnormalities are particularly frequent with this drug. Layton et al reported significant blood changes in 35% of their patients and, in one report, macrocytosis and a reduced red cell count, although not anaemia, were seen in 4 of 5 patients treated. These side effects may develop after several months of treatment. They have generally been reversible after discontinuation of the drug. Since hydroxycarbamide is largely excreted in the urine, extra caution is required if renal function is impaired. It may occasionally cause fever. Cutaneous side effects of hydroxycarbamide include partial alopecia, increased pigmentation, scaling, atrophy, nail changes, erythema of the face and hands, and a lichenoid eruption. Hydroxycarbamide is a cytotoxic drug with potential for teratogenic effects and is best avoided in women of child-bearing age. Monitoring
It is recommended that patients should have their full blood count, including platelet count and differential white cell count, checked prior to commencing the drug and, at least, weekly intervals for at least the first six weeks. Subsequently, the intervals between haematological assessments may be gradually extended, provided there is no cause for concern. The maximal interval should not exceed three months. Serum creatinine and liver function tests should also be monitored. It would also seem prudent to examine patients every six months for evidence of malignancy and to advise females to attend, when called, for routine cervical smears. References
Leavell UW, Yarbro JW. Hydroxyurea. A new treatment for psoriasis. Arch Dermatol 1970; 102: 144- 50. Moschella SL, Greenwald MA. Psoriasis with hydroxyurea. An 18-month study of 60 patients. Arch Dermatol 1973; 107: 363-8. Lebwohl M, Menter A, Koo J, Feldman SR. Combination therapy to treat moderate to severe psoriasis. J Am Acad Dermatol. 2004 Mar;50(3):416-3
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