Pancytopenia due to Paludrine® (Proguanil Hydrochloride)

M.H.M.G. Houben, MD, Department of Internal Medicine, Catharina Hospital, Michelangelolaan 2, NL-5602 ZA Eindhoven (The Netherlands) Dear Sir, We wish to report on severe pancytopenia in a renal transplant recipient with chronic renal failure that occurred after administration of Paludrine® (proguanil hydrochloride; in the following referred to as proguanil) as a prophylactic antimalarial drug and to present hitherto unpublished dosage recommendations for proguanil in patients with renal impairment. A 25-year-old man went to India in July 1993 for a fortnight holiday. He received proguanil as antimalarial prophylaxis at a daily dosage of 200 mg. His original renal diagnosis was endocapiUary proliferative glomerulonephritis; this disease recurred in both renal transplants (1985 and 1992). One week before departure, the serum creatinine concentration was 398 μmol/l (creatinine clearance 10 ml/min). His additional medication included furosemide, felodipine, alu-col, disodium pamidronate, calcitriol, pred-nisone, and immuran (100 mg daily). SponTable 1. Recommended dosage of proguanil in patients with renal impairment Proguanil dosage Creatinine clearance ml/min/1.73 m2 200 mg once daily 100 mg once daily 50 mg every 2nd day 50 mg once weekly > 60 20-60 10-20 < IO taneous haemorrhages and epistaxis developed 2 weeks after receiving proguanil. Upon admission to our hospital he appeared pale, cushingoid, and dehydrated. Laboratory findings included anaemia (haemoglobin 5.0mmol/l), leucopenia (leucocytes 2.7/nl) with granulopenia (1.28/nl), and thrombope-nia (17/nl). The serum creatinine level had increased to 641 μmol/l. It was concluded that the pancytopenia was caused by a proguanil intoxication. Proguanil and immuran were withheld; additional treatment included thrombocyte concentrates, rehydration, and folic acid. Renal replacement therapy had to be restarted. Both thrombopenia and leucopenia disappeared after 10 days. He eventually made a full recovery though maintenance therapy had to be continued. Proguanil is generally considered a safe and effective antimalarial drug with few reported side effects [1]. To our knowledge, only two reports of three similar cases with renal impairment and pancytopenia caused by proguanil have been published [2,3]. Proguanil and its active metabolite cycloguanil, a potent inhibitor of dihydrofolate reduc-tase, are predominantly excreted by the kidneys [4, 5]. Therefore, accumulation of the drug is to be anticipated in patients with renal failure, and the dosage has to be adapted in patients with