Reported Adverse Drug Reaction Cases
- ADRAC, Thomas M. Diuretics, ACE inhibitors and NSAIDs - the triple whammy. MJA 2000; 172: 184-5.
- Boyd IW, Mathew TH, Thomas MC. COX-2 inhibitors and renal failure: the triple whammy revisited. MJA 2000; 173: 274 (corr. MJA 2000; 173: 504).
- ADRAC. ACE inhibitor, diuretic and NSAID: a dangerous combination. Aust Adv Drug React Bull 2003; 22: 14-15.
Beware the triple whammy!
ADRAC has previously warned prescribers about the 'triple whammy' - the combination of an ACE inhibitor (ACEI) or an angiotensin II receptor antagonist (A2RA), a diuretic and an NSAID (including a COX-2 selective NSAID), which may predispose vulnerable patients to renal failure.1,2,3 Risk factors include advanced age, pre-existing renal impairment and dehydration. In 2005, ADRAC received 21 reports of renal failure in patients who were exposed to the triple whammy. In a number of cases, precipitating factors included an acute illness, dehydration, digoxin toxicity or the recent addition of an NSAID to a patient already on an ACEI or an A2RA and a diuretic.
The National Prescribing Service (NPS) has recently released Indicators of Quality Prescribing in Australian General Practice: a manual for users, available from the NPS website. One of the process indicators is entitled Good prescribing (avoiding the 'triple whammy') and reinforces the message that risk of the triple whammy should be avoided if possible and extreme caution should be taken with ACEIs or A2RAs and NSAIDs in patients with renal impairment.
It should be remembered that there are now many combination products available that contain both an ACEI or an A2RA and a diuretic.
Some of the more commonly used combinations are shown in the Table. ADRAC advises that prescribers avoid the triple whammy where possible. However, if these drugs are necessary, prescribers should be alert for situations such as illness, dehydration or initiation of an NSAID, which may predispose patients on this combination to renal failure, and advise patients to seek medical advice during such episodes.
|ACEI or A2RA/diuretic combination||Product name/s|
|Perindopril/indapamide||Coversyl Plus; Perigard-D; Perigard-DF|
|Enalapril/HCT||Renitec Plus; Enace-D; Enapril-HT; Enzide; Invozide; Normace-D;Tenam-HT; Vasonorm-H; Viviril-D|
|Captopril/HCT||Capozide; Coverex Plus; Angiopril-DU|
|Irbesartan/HCT||Avapro HCT; Karvezide; Irovel-H; Xarb-H|
|Telmisartan/HCT||Micardis Plus; Pritor Plus; Telmitop HC; Telsar-H; Telvas-H|
HCT - hydrochlorothiazide; Entries in Bold are of Indian Brands
Australian Adverse Drug Reactions Bulletin, Volume 5, Number 5, October 2006