494 BRITISH MEDICAL JOURNAL VOLUME 284 13 FEBRUARY 1982 Br Med J (Clin Res Ed): first published as 10.1136/bmj.284.6314.494 on 13 February 1982. Downloaded from Lesson of the Week

Ventricular fibrillation induced by xipamide

PAUL ALTMANN, J J HAMBLIN

Xipamide (Diurexan) and indapamide (Natrilix) have been introduced as new antihypertensive agents. They are marketed Any diuretic, unless specifically a potassium- as being more effective than the thiazide diuretics but not as sparing one, may cause profound hypokalaemia potent as beta-blockers. They are both thiazide-related, being chemically similar to chlorthalidone. It is claimed that they lower blood pressure without causing an appreciable diuresis, and that the incidence of hypokalaemia in hypertensive patients is remained normal. Her progress was complicated by a chest much lower than with the other thiazide diuretics. Thus many infection, but she is now well and continues to attend for patients have been started on treatment with one of these two follow-up. drugs, and they are especially popular with general practitioners because the regimen is one tablet a day.1 2 Patients who are referred to our outpatient department or who come as inpatients Discussion taking these drugs are frequently severely hypokalaemic and moreover are symptomatically so. Xipamide and indapamide should not cause such profound problems, according to the manufacturers.3 The results of studies of the treatment of hypertension with these two drugs have shown that plasma potassium concentrations remained well Case report within the normal range, even without supplementation, or that On 26 August 1981 a woman aged 64 was brought to the at the usual dose for hypertension potassium supplementation accident centre having collapsed. She was semiconscious and had would not normally be an essential part of treatment5-7; and multifocal ectopic beats with short runs of ventricular tachy- "side effects have not been a problem with xipamide administra- cardia. Before any treatment could be started she developed tion."' Nevertheless, other studies have shown the equipotency ventricular fibrillation, which immediately responded to a DC of xipamide as compared to other diuretics such as frusemide and shock of 200 joules. She continued to have an alarming number chlorthalidone,9 and one such study showed that "potassium of multifocal ventricular ectopic beats, and her mental state excretion was greater following xipamide in the dose of 40 mg remained unchanged. She was started on maximal doses of than after 50 mg of hydrochlorthiazide, the difference being http://www.bmj.com/ lignocaine. After she was admitted to the cardiac care unit it statistically significant" (F Kruck, data files, E Merck Ltd). was discovered that her general practitioner had been treating Thus, the findings on the subject seem to be contradictory. her for hypertension since February with xipamide 20 mg per We feel strongly that neither xipamide nor indapamide day. During the week before admission she had become in- should be marketed as hypotensive diuretics that do not require creasingly unwell, with generalised weakness and muscle pains potassium supplements. These drugs are potent diuretics. and had seen her general practitioner the day before. On admission her plasma potassium concentration was We have reported this -case to the Committee on Safety of 1-2 mmol(mEq)/l, with a bicarbonate of more than 40 mmol Medicines. on 27 September 2021 by guest. Protected copyright. (mEq)/l. She was very confused and restless after defibrillation and was started on 80 mmol of potassium per hour intravenously and the electrolyte concentration estimated hourly. In one hour References had disappeared, and she the multifocal ectopics completely 1 Weber JCP, et al. Once daily treatment of mild to moderate hypertension remained in sinus rhythm thereafter. She remained severely with xipamide: a controlled study. Br J7 Clin Pharmacol 1977 ;4 :283-8. hypokalaemic, however, and required a total of 760 mmol of 2 Murphy MA, Bowker CH. The use of indapamide in the UK (general potassium intravenously in the first 24 hours. The plasma practice multicentre study). International symposium on hypertension rose to 4-4 and her mental and Natrilix, October 1979. potassium concentration then mmol, 3Diurexan, anti-hypertensive diuretic. E Merck Limited. 1981. state returned to normal. Intravenous treatment was stopped, 4 Natrilix: a development on the diuretics in the treatment of hypertension. but her plasma potassium concentration dropped again to Servier Laboratories Limited. 1980. 2-4 mmol(mEq)/l, and she was started on oral supplements of 5Castro M. Xipamide (Diurexan) in essential hypertension: a 24 month 36 mmol per day as effervescent potassium tablets. After two study. Curr Med Res Opin 1980;6:416-22. 6Lentini S, et al. Clinical trial ofxipamide in the treatment of hypertension. days her plasma potassium concentration had once more Jf Int Med Res 1980;8:38-43. returned to normal, and her electrolytes subsequently have 7Anavekar SN, et al. Evaluation of indapamide in the treatment of hyper- tension. 3rournal of Cardiovascular Pharmacology 1979;1:389-94. 8 Davies PS, Prichard BNC. A dose-response study of xipamide in hyper- tension used in combination with other anti-hypertensive drugs. Y Int Med Res 1975;3:389-94. Southend Hospital, Essex SSO ORY 9 Hempelman FW, Leuschner F, Liebenow W. The saluretic effect of PAUL ALTMANN, medical registrar xipamide in normal subjects. Arzneimittelforsch 1975;25:2. J J HAMBLIN, FRCP, consultant physician (Accepted 3 November 1981)