Hyperkalaemia associated with hydroxyurea in a patient with polycythaemia vera

Abstract

Hydroxyurea has been used for decades for the treatment of some types of malignancies [1]. It has been demonstrated to be very effective in preventing thrombosis and thus should be considered as first-line therapy in high-risk patients with myeloproliferative disorders [2]. An 81-year-old woman was admitted to hospital in December 2009 because of hyperkalaemia. Her medical history included essential hypertension for the last 15 years. She had been diagnosed with polycythaemia vera in April 2007 and an initial treatment consisted of phlebotomy and low-dose acetylsalicylic acid. In May 2009 the patient had developed iliofemoral vein thrombosis as a consequence of polycythaemia vera. To prevent further thromboembolic complications, therapy with hydroxyurea had been introduced. At the time of admission, the patient's therapy included ramipril (2.5 mg), acetylsalicylic acid (100 mg) and hydroxyurea (1,000 mg) daily. Serum potassium level was 6.7 mmol/L (normal range 3.9–5.1 mmol/L). Levels of sodium, chloride, calcium, lactate dehydrogenase and creatine kinase were all within normal values. Haemoglobin concentration, haematocrit, white and red blood cells and platelet count were normal as were values for plasma aldosterone, plasma renin activity and 24-h urinary free cortisol. Arterial blood pH and bicarbonates were mildly decreased (pH 7.318, bicarbonates 18.9 mmol/L). Patient's renal function was decreased with serum creatinine of 116 μmol/L and 24-h creatinine clearance of 41.7 ml/min. Electrocardiogram (ECG) showed no abnormality. Since there was no significant difference between the serum and plasma potassium levels, pseudohyperkalaemia could be excluded [3]. Because of the possibility that hyperkalaemia was caused by ramipril or acetylsalicylic acid, therapy with these drugs was discontinued. Repetitive administration of bicarbonate and insulin/glucose did not decrease the potassium level and after 7 days it remained high (5.8–6.4 mmol/L). The degree of hyperkalaemia could not have been explained by moderate renal insufficiency and the clinical investigation did not find any other possible cause. Thus, we suspected that it could have been caused by an adverse reaction to hydroxyurea. Therapy with hydroxyurea was discontinued and 2 days later the potassium level decreased to 5.0 mmol/L. Since hyperkalaemia was not listed as an adverse reaction in the Summary of Product Characteristics and no similar cases have been reported in the literature, we were not convinced that it was really caused by hydroxyurea. Hyperkalaemia was asymptomatic and caused no ECG changes in the presented case; thus, we believed that rechallenge would not endanger the patient. After Ethics Review Board approval she was re-administered 500 mg of hydroxyurea daily. After the second dose, the serum potassiS. Marusic (*) :N. Gojo-Tomic Department of Clinical Pharmacology, University Hospital Dubrava, Av. Gojka Suska 6, 10000 Zagreb, Croatia e-mail: srmarusic@inet.hr