SHARED CARE GUIDELINE 1
HYDROXYCARBAMIDE
INTRODUCTION
Hydroxycarbamide has a number of licensed indications all of which are not suitable for shared care. This guideline includes treatment for the following:
Psoriasis - Hydroxycarbamide is a second line agent that is sometimes used for severe psoriasis. It is usually reserved for cases where other second line agents have failed or are contraindicated. It may also be used in conjunction with the drug acitretin. Hydroxycarbamide avoids the hepatotoxicity associated with methotrexate and the nephrotoxicity associated with ciclosporin.
Sickle cell anaemia - Hydroxycarbamide is given primarily to reduce the incidence of painful episodes by either increasing the Haemoglobin F% or by alterations in RBC hydration. It may also: • Increase the haemoglobin concentration • Prevent or possibly reverse chronic organ damage • Reduce the incidence of the acute chest syndrome • Decrease the need for blood transfusion • Reduce mortality (40% decrease over 6-8 years follow up)
Myeloproliferative disorders – e.g. Primary Proliferative Polycythaemia (PRV), Essential Thrombocythaemia and Chronic Myeloid Leukaemia (CML).
DOSE AND ADMINISTRATION
Psoriasis - Generally 0.5 – 1.5g daily, orally either as a single dose, or divided into two doses (morning and evening).
Sickle cell anaemia - Initial dose 15mg/kg/day . Increase dose by increments of 5mg/kg/day every 6 weeks provided blood values are in the acceptable range until a haematologically safe stable dose is established. Maximum dose should not exceed 35mg/kg/day .
Hydroxycarbamide is available as 500mg capsules
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.
CAUTIONS
Should be administered with caution to patients who receive concomitant or have received previous therapy with other antineoplastic drugs or irradiation. Haematological impairment. Renal or hepatic impairment. In general patients should try to avoid ‘live’ vaccines such as oral polio, MMR, BCG and yellow fever (passive immunization should be carried out using Varicella zoster immunoglobulin (VIZIG) in non-immune patients exposed to active chickenpox or shingles). CONTRA-INDICATIONS
Blood dyscrasias {marked leucopenia (wbc<2.5x10 9/L), thrombocytopenia(< 100x10 9/L), severe anaemia} Previous hypersensitivity to hydroxycarbamide. Pregnancy and lactation, Genotoxic - therefore, men and women under therapy are advised to use safe contraceptive measures during and for at least 3 months after therapy. Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. SHARED CARE GUIDELINE 2
SIDE- EFFECTS
Acute leukaemia has occurred in patients receiving hydroxycarbamide for PRV, however it is generally considered that this is due to disease progression and is NOT an effect of the drug itself. 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, especially when used with other cytotoxic agents.
See Summary of Product Characteristics for comprehensive list.
MONITORING STANDARDS FOR HYDROXYCARBAMIDE The following standards have been agreed for the monitoring of hydroxycarbamide.
In dermatology: Pre -treatment FBC, LFTs, U&Es, Uric acid, GammaGT, Smear test.
Monitoring FBC, LFT, U&Es, GammaGT, Urinalysis, weekly initially for 2 months then monthly if stable
Uric acid, every 3 months
Creatinine clearance, perform if renal function tests are abnormal or urinalysis positive to blood and protein or when indicated by doctor.
In haematology: Pre -treatment Haemoglobin concentration + reticulocyte count, Haemoglobin S%, Haemoglobin F%, neutrophil count, platelet count, creatinine and AST.
Monitoring FBC + reticulocytes, U&Es, LFTs and Haemoglobin F% every 2 weeks until a haematologically safe & stable dose is achieved then every month.
EVENTS AND ACTION
Laborat ory Events Values Action • Serum creatinine >150 µmol/L • Haemoglobin < 4.5* g/dl (limit applicable to sickle cell Stop + seek advice. anaemia patients only) • Neutrophils < 2.0 x 10 9 /L • Reticulocytes < 80** x 10 9 /L • Platelets < 80 x 10 9 /L • Elevation in liver enzymes (AST, ALT,GGT) Serial rise over 3 visits * Values between 4.5 and 5.3 g/dl are not considered toxic provided the reticulocyte count is > 320 x 109 /L ** Not considered toxic if the haemoglobin concentration is >9.0 g/dl.
Symptoms Management • Skin changes Stop and discuss with specialist. • Fever and hepatitis • Hyper pigmentation of skin and nails This is common and is not an indication for stopping treatment.
• Development of gout or, at worst, uric acid Monitor uric acid levels regularly and advise patient to maintain a nephropathy (especially when used with high fluid intake during treatment. other cytotoxic agents)
REMEMBER if unsure at any point: Contact the various Specialists and or Specialist Nurse/Nurse Practitioner via the Homerton Hospital switchboard on 020 8510 5555.