Amiloride
Sources réglementaires consultées
Indications approuvées
- Traitement adjuvant à un thiazidique ou à un autre diurétique kaliurétique dans l'insuffisance cardiaque congestive ou l'hypertension afin de corriger ou prévenir l'hypokaliémie, notamment lorsque son évitement est important, par exemple chez les patients sous digitaliques ou présentant des arythmies.
Contre-indications
Absolues
- Kaliémie supérieure à 5,5 mEq/L.
- Utilisation concomitante d'autres diurétiques épargneurs de potassium.
- Suppléments de potassium ou substituts de sel contenant du potassium, sauf hypokaliémie sévère ou réfractaire sous surveillance étroite.
- Anurie, insuffisance rénale aiguë ou chronique et néphropathie diabétique.
- Hypersensibilité à l'amiloride.
Mises en garde cliniques
- Mise en garde encadrée · Une hyperkaliémie potentiellement mortelle peut survenir, surtout en cas d'insuffisance rénale, de diabète et chez le sujet âgé. Surveiller la kaliémie à l'instauration, après les modifications de dose et lors de maladies affectant la fonction rénale. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0cc2d44-436a-47e8-a890-589882fff4c4
- Mise en garde majeure · Si l'urée sanguine dépasse 30 mg/dL, si la créatinine sérique dépasse 1,5 mg/dL ou en cas de diabète, ne pas utiliser sans surveillance fréquente et rigoureuse des électrolytes, de la créatinine et de l'urée. — DailyMed setid e0cc2d44-436a-47e8-a890-589882fff4c4
- Mise en garde majeure · Une hyperkaliémie peut survenir chez les patients diabétiques même sans néphropathie diabétique reconnue. Éviter l'amiloride si possible ; s'il est utilisé, surveiller fréquemment les électrolytes et la fonction rénale. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0cc2d44-436a-47e8-a890-589882fff4c4
- Mise en garde majeure · Chez les patients gravement malades exposés à une acidose métabolique ou respiratoire, n'instaurer le traitement antikaliurétique qu'avec prudence et surveiller fréquemment l'équilibre acido-basique, car l'acidose peut augmenter rapidement la kaliémie. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0cc2d44-436a-47e8-a890-589882fff4c4
- Mise en garde majeure · En cas d'hépatopathie sévère préexistante, une encéphalopathie hépatique avec tremblements, confusion ou coma et une aggravation de l'ictère ont été rapportées avec les diurétiques, y compris l'amiloride ; surveiller étroitement. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e0cc2d44-436a-47e8-a890-589882fff4c4
Interactions médicamenteuses
- SévèreIEC, ARA-II, ciclosporine ou tacrolimus
Mécanisme: La rétention additive de potassium augmente le risque d'hyperkaliémie.
Recommandation: Éviter si possible ; en cas d'association, surveiller étroitement la kaliémie et la fonction rénale.
DailyMed setid e0cc2d44-436a-47e8-a890-589882fff4c4
- SévèreLithium
Mécanisme: Les diurétiques réduisent la clairance du lithium et augmentent sa toxicité.
Recommandation: Éviter généralement ; en cas d'association, surveiller les concentrations de lithium.
DailyMed setid e0cc2d44-436a-47e8-a890-589882fff4c4
- ModéréeAnti-inflammatoires non stéroïdiens
Mécanisme: Ils peuvent réduire les effets diurétique et antihypertenseur ; l'indométacine peut augmenter la kaliémie et le risque rénal.
Recommandation: Surveiller la réponse, la kaliémie et la fonction rénale.
DailyMed setid e0cc2d44-436a-47e8-a890-589882fff4c4
Effets indésirables
Communs (≥1%)
Céphalées · Nausées ou anorexie · Diarrhée · Vomissements · Faiblesse · Fatigue · Douleur abdominale · Crampes musculaires
Rares mais graves
Hyperkaliémie avec arythmie · Ictère · Hémorragie gastro-intestinale · Encéphalopathie
Grossesse et allaitement
Pendant la grossesse, n'utiliser qu'en cas de nécessité clairement établie. Pendant l'allaitement, les données animales montrent un passage dans le lait ; décider d'interrompre l'allaitement ou le médicament selon son importance clinique.
Bibliographie récente (PubMed)
Nephrogenic diabetes insipidus (NDI) is characterized by the inability to concentrate urine that results in polyuria and polydipsia, despite having normal or elevated plasma concentrations of arginine vasopressin (AVP). In this study, we review the clinical aspects and diagnosis of NDI, the various etiologies, current treatment options and potential future developments. NDI has different clinical manifestations and approaches according to the etiology. Hereditary forms of NDI are mainly caused by mutations in the genes that encode key proteins in the AVP signaling pathway, while acquired causes are normally associated with specific drug exposure, especially lithium, and hydroelectrolytic disorders. Clinical manifestations of the disease vary according to the degree of dehydration and hyperosmolality, being worse when renal water losses cannot be properly compensated by fluid intake. Regarding the diagnosis of NDI, it is important to consider the symptoms of the patient and the diagnostic tests, including the water deprivation test and the baseline plasma copeptin measurement, a stable surrogate biomarker of AVP release. Without proper treatment, patients may developcomplications leading to high morbidity and mortality, such as severe dehydration and hypernatremia. In that sense, the treatment of NDI consists in decreasing the urine output, while allowing appropriate fluid balance, normonatremia, and ensuring an acceptable quality of life. Therefore, therapeutic options include nonpharmacological interventions, including sufficient water intake and a low-sodium diet, and pharmacological treatment. The main medications used for NDI are thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and amiloride, used isolated or in combination.
Amiloride has been proposed as an alternative to spironolactone for treating resistant hypertension. However, no randomized clinical trials have compared the efficacy of spironolactone and amiloride in patients with resistant hypertension. To determine whether amiloride is noninferior to spironolactone in reducing home-measured systolic blood pressure (SBP) in patients with resistant hypertension. Prospective, open-label, blinded end-point randomized clinical trial conducted at 14 sites in South Korea. From November 16, 2020, to February 29, 2024, 118 patients with home SBP of 130 mm Hg or greater after a 4-week run-in period with a fixed-dose triple medication combination (angiotensin receptor blocker, calcium channel blocker, and thiazide) were enrolled. Patients were randomized in a 1:1 ratio to receive 12.5 mg/d of spironolactone (n = 60) or 5 mg/d of amiloride (n = 58). If home SBP remained 130 mm Hg or greater and serum potassium was less than 5.0 mmol/L after 4 weeks, dosages were increased to 25 mg/d and 10 mg/d, respectively. The primary end point was the between-group difference in home SBP change at week 12, with a noninferiority margin of -4.4 mm Hg for the lower bound of the confidence interval. Secondary end points included achievement rates of home- and office-measured SBP of less than 130 mm Hg. The median age of the study population was 55 years, with 70% male. There were no differences between groups in demographic characteristics other than use of α-blockers (8.6% in the amiloride group and 0% in the spironolactone group). The mean baseline home SBPs were 141.5 (SD, 7.9) mm Hg and 142.3 (SD, 8.5) mm Hg in the amiloride and spironolactone groups, respectively. At week 12, mean home SBP measurements were changed from baseline by -13.6 (SD, 8.6) mm Hg and -14.7 (SD, 11.0) mm Hg in the amiloride and spironolactone groups, respectively (between-group difference in change, -0.68 mm Hg; 90% CI, -3.50 to 2.14 mm Hg), with amiloride demonstrating noninferi
Resistant hypertension is a condition where blood pressure levels remain elevated above target despite changes in lifestyle and concurrent use of at least three antihypertensive agents, including a long-acting calcium channel blocker (CCB), a blocker of the renin-angiotensin system (ACE inhibitor or angiotensin receptor blocker) and a diuretic. To be diagnosed as resistant hypertension, maintaining adherence to therapy is required along with confirmation of blood pressure levels above target by out-of-office blood pressure measurements and exclusion of secondary causes of hypertension. The key management points of this condition include lifestyle changes such as reduced sodium and alcohol intake, regular physical activity, weight loss and discontinuation of substances that can interfere with blood pressure control. It is also recommended that current treatment be rationalised, including single pill combination treatment where antihypertensive drugs should be provided at the maximum tolerated dose. It is further recommended that current drugs be replaced with a more appropriate and less difficult treatment regimen based on the patient's age, ethnicity, comorbidities and risk of drug-drug interactions. The fourth line of treatment for patients with resistant hypertension should include mineralocorticoid receptor antagonists such as spironolactone, as demonstrated in the PATHWAY-2 trial and meta-analyses. Alternatives to spironolactone include amiloride, doxazosin, eplerenone, clonidine and beta-blockers, as well as any other antihypertensive drugs not already in use. New approaches under research are selective non-steroidal mineralocorticoid receptor antagonists such as finerenone, esaxerenone and ocedurenone, selective aldosterone synthase inhibitors such as baxdrostat, and dual endothelin antagonist aprocitentan. Amiloride is a potassium-sparing diuretic used in the therapy of edema often in combination with thiazide diuretics. Amiloride has been linked to rare case