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Vol. 31. Issue. 1.January 2011
Pages 1-128
Vol. 31. Issue. 1.January 2011
Pages 1-128
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Severe acute hypokalaemia secondary to voriconazole. Uncommon pharmacological causes of hypokalaemia
Hipopotasemia severa aguda secundaria a voriconazol. Causas farmacológicas infrecuentes de hipopotasemia
, M.. González Rozasb, S.. Álvarez Tundidorc, M.. Pineda Alonsod
b Servicio de Medicina Interna, Hospital Vega Baja, Alicante,
c Servicio de Nefrolog??a, Hospital Virgen de la Concha, Zamora,
d Servicio de Medicina Interna, Hospital R??o Hortega, Valladolid,
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To the Editor,

Hypokalaemia is one of the most common metabolic disorders in clinical practice. We report the case of a man who had acute severe hypokalaemia secondary voriconazole, which was resolved without incident.

Hypokalaemia is defined as a decrease in plasma potassium to below 3.5mmol/l and is one of the most common metabolic disorders in clinical practice. Drugs are one of the most common causes of hypokalaemia, primarily through two mechanisms: they promote the movement of potassium into the cell and increase its renal elimination.1

We report the case of a 62-year-old man with a 15-year history of sporadic cerebellar ataxia, without other diseases, who arrived at the emergency department with a fever of one week duration. During admission, he had severe acute respiratory failure secondary to bilateral pneumonia. Treatment was initiated with linezolid, amikacin and piperacillin/ tazobactam empirically. A bronchoscopy was performed with sampling, from which Candidaspp. were isolated, therefore voriconazole was added to the treatment. A control analysis was performed before the introduction of antifungal agents which showed the red cells, white cells, platelets and coagulation were normal. In the biochemical analysis, renal function, liver function and ions showed no abnormalities. At 24 hours after initiation of the voriconazole treatment, the patient had potassium levels of 2.1mmol/l without any associated clinical or electrocardiographic abnormalities. Intravenous replacement with potassium chloride and oral supplements was initiated, and the potassium values returned to normal at 3 days.

In this case, the patient was taking 2 drugs that might predispose a decrease in potassium levels: an aminoglycoside,2 whose tubular toxicity effect has been widely described, and linezolid, which rarely causes hypokalaemia.3 The levels were normal with both drugs, but there was a severe, acute fall after adding voriconazole, without severe repercussions for the patient.

Voriconazole is a broad spectrum, antifungal agent in the azole family. It has excellent bioavailability, both orally and intravenously. It is metabolised in the liver by the cytochrome P-450 pathway and its metabolites have no antifungal activity. A dose adjustment is needed in patients with moderate liver function impairment. Renal clearance was 85% as inactive metabolites. In addition, the elimination of unmetabolised voriconazole is slight, so the oral formulation does not require dosage adjustment in kidney failure. However, intravenous administration should be avoided in patients with creatinine clearance below 50ml/min, as its excipient, cyclodextrin, can accumulate.4

Voriconazole is well tolerated. The most common side effect, unique among the azoles, is a reversible disturbance of vision, photopsia, which does not usually require discontinuation of the therapy. The following side effects are photosensitivity and increased liver enzyme levels. Less common are vomiting, diarrhoea, abdominal pain and visual hallucinations. Due to its hepatic metabolism, voriconazol can interact with numerous medications.2

Hypokalaemia is not a common side effect. Studies have compared it to amphotericin B, the prevalence of hypokalaemia is 18.8% and only 2.4% have potassium levels below 2.5mmol/l.3,5

Many new drugs are increasingly being reported to be involved in various electrolyte disturbances (Table 1). Therefore, the medication that all patients with hypokalaemia receive should be examined, including both drugs traditionally associated with hypokalaemia, such as diuretic agents, beta-adrenergic agonists and amphotericin B, and new antibiotic, antiretroviral and immunosuppressant drugs.


Table 1. Drugs leading to hypokalaemia

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Tejada-Cifuentes F. Alteraciones del equilibrio del potasio: hipopotasemia. Rev Clin Med Fam 2008;2(3):129-33.
Mac??as-Garrido E, Garc??a-Frade F. Hipopotasemia en pacientes hospitalizados. Med Int Mex 2008;24(1):3-7.
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Walsh T, Pappas P,??Winston DJ,??Lazarus HM,??Pettersen F,??Raffalli J,??et al. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 2007; [Pubmed]
Nefrología (English Edition)

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