Long-term use and tolerability of Irbesartan for control of hypertension

INTRODUCTION:

The renin-angiotensin-aldosterone system (RAAS) is one of the most complex and important systems in controlling the blood pressure and fluid balance in the body. Dysregulation of the RAAS plays an important role in the pathogenesis of cardiovascular and renal disorders such as hypertension, myocardial infarction, heart failure, and chronic kidney disease. Angiotensin receptor blockers (ARBs) have been available for management of hypertension.

Irbesartan is a well-established angiotensin receptor blocker, approved worldwide for the treatment of hypertension. It lowers blood pressure over 24 hours. The usual starting dosage is 150 mg once daily and can be up titrated to 300 mg once daily. It is also approved for the treatment of nephropathy in patients with hypertension and type 2 diabetes mellitus. 300 mg once daily is the recommended maintenance dosage.

RELEVANCE:

Angiotensin-receptor blockers (ARBs) is an effective antihypertensive agent with an impressive safety profile and placebo-like tolerability. It provides benefits beyond the reduction in blood pressure in relation to heart failure, type II diabetes and renal insufficiency. Irbesartan, an ARB is recognized by national and international guidelines management of hypertension with or without type 2 diabetes or renal disease.

OBJECTIVES:

To determine the pharmacokinetic and pharmacodynamics characteristic of ARBs which focuses on recent clinical evidences and studies about the therapeutic efficacy and tolerability of Irbesartan when used as an oral monotherapy or combination therapy in essential hypertension, diabetic nephropathy and cardiac disease.

HIGHLIGHTS:

Irbesartan in monotherapy is found to be very effective in lowering both systolic and diastolic blood pressure. It is effective in producing a sustained 24-hour blood pressure control. It’s effect on blood pressure manifest within 2 weeks starting treatment and achieved maximum reduction after 2-6 weeks. In cases if mild-to-moderate hypertension, it also showed equal efficacy but better tolerability compared with other major antihypertensive classes.

Another study showed results that Irbesartan does not also affect renal hemodynamics and renal salt handling when combined with COX-2 inhibitors. It is strictly contraindicated in the second and third trimester of pregnancy and during lactation and it has been found to induce renal vasodilatation without altering glomerular filtration rate, to improve endothelial function, and to reduce oxidative stress and inflammation in the kidney.

Irbesartan improved microalbuminuria also in a normotensive subgroup of diabetic patients with early stage microalbuminuric nephropathy and significantly reduced QT and corrected QT interval dispersion with a reduction in the risk of arrhythmias in cardiac disease. A dosage of 150-300 mg once daily was found to induce greater left ventricular mass index regression.

Irbesartan as monotherapy or as combination therapy with hydrocholorthiazide was associated with low discontinuation rates for adverse events and low incidences of serious adverse events. Persistence with a drug can be regarded as a good general indicator of the satisfaction of both patients and physicians with the efficacy and tolerability of the treatment.

CONCLUSION:

Irbesartan is an effective antihypertensive drug in variety of mild – to – moderate hypertensive population. It is found to be effective on patients with diabetes, obesity, renal insufficiency and cardiovascular disease. Its action slows the progression of early stage and late stage renal disease in hypertensive patients with type 2 diabetes and reduces the risks of heart failure episodes. Treatment with Irbesartan in hypertensive patients with type 2 diabetes and nephropathy resulted in improved life expectancy and appeared to be cost-saving and scores well for patient acceptation and adherence rates.