Olmesartan (Benicar, Olmecip)

Indications

Congestive Heart Failure (CHF) (see Congestive Heart Failure, [[Congestive Heart Failure]])
Diabetic Nephropathy (see Diabetes Mellitus, [[Diabetes Mellitus]])
Hypertension (see Hypertension, [[Hypertension]])

Pharmacology

Angiotensin II Receptor Blocker (ARB) (see Angiotensin II Receptor Blockers, [[Angiotensin II Receptor Blockers]])

Metabolism

xxx

Administration

PO: xxx

Dose Adjustment

Hepatic
Renal

Concomitant Administration of ACE Inhibitors and ARBS

Combination ACE Inhibitor and ARB Therapy Increases the Risk of Adverse Effects [MEDLINE]: including hyperkalemia, medication discontinuation due to adverse effects, worsened renal function, and symptomatic hypotension
- Combination ACE Inhibitor and ARB Therapy Does Not Increase the Rate of Malignancy [MEDLINE]
- Recommendation: it is recommended to not use combination ACE inhibitor and ARB therapy

Adverse Effects

Allergic/Immunologic Adverse Effects

Angioedema (see Urticaria-Angioedema, [[Urticaria-Angioedema]])

Epidemiology: less common with ARB’s than with ACE inhbitors
- Telmisartan (0.1%) has a lower incidence of angioedema than ramipril (0.3%) [MEDLINE]
- Cross-Reactivity
  - In patients with ACE-inhibitor-associated angioedema, the risk of development of any subsequent ARB-associated angioedema is 2-17%
  - In patients with ACE-inhibitor-associated angioedema, the risk of development of subsequent confirmed ARB-associated angioedema is 0-9.2%
Physiology: class effect (common to all ARB’s)

Cardiovascular Adverse Effects

Hypotension (see Hypotension, [[Hypotension]])

Epidemiology: more common with ARB’s than with ACE inhibitors
- Telmisartan has significantly higher rate of symptomatic hypotension (2.6%) vs ramipril (1.7%) [MEDLINE]
Physiology: class effect (common to all ARB’s)
- Due to basic pharmacology of ARB’s

Syncope (see Syncope, [[Syncope]])

Epidemiology: ramipril (0.2%) and telmisartan (0.2%) have similar rates of syncope requiring discontinuation of the drug [MEDLINE]

Endocrinologic Adverse Effects

Drug-Induced Hypoaldosteronism (see Hypoaldosteronism, [[Hypoaldosteronism]])
- Hyperkalemia (see Hyperkalemia, [[Hyperkalemia]])
- Non-Anion Gap Metabolic Acidosis (see Metabolic Acidosis-Normal Anion Gap, [[Metabolic Acidosis-Normal Anion Gap]])

Gastrointestinal Manifestations

Sprue-Like Enteropathy

Epidemiology: occurs months-years after initiation of drug
Clinical
- Diarrhea
- Weight Loss
Treatment: resolves after discontinuation of olmesartan
Rechallenge with Olmesartan: sometimes results in recurrence of the symptoms

Pulmonary Adverse Effects

Cough (see Cough, [[Cough]])

Epidemiology: less common with ARB’s than with ACE-Inhibitors
- Ramipril has higher incidence of cough (4.2%) than telmisartan (1.1%) [MEDLINE]
Physiology: class effect (common to all ARB’s)

Renal Adverse Effects

Acute Kidney Injury (AKI) (see Acute Kidney Injury, [[Acute Kidney Injury]])

Epidemiology
- Ramipril (1.9%) and telmisartan (2.0%) demonstrate similar rates of AKI, as defined by doubling of serum creatinine [MEDLINE]

Hyperkalemia (see Hyperkalemia, [[Hyperkalemia]])

Epidemiology: similar rates of hyperkalemia are observed with ramipril (3.3%) and telmisartan (3.4%) [MEDLINE]
Physiology: due to drug-induced hypoaldosteronism (see above)

Non-Anion Gap Metabolic Acidosis (see Metabolic Acidosis-Normal Anion Gap, [[Metabolic Acidosis-Normal Anion Gap]])

Physiology: due to drug-induced hypoaldosteronism (see above)

Other Effects

ARBS’s Do Not Increase the Risk of Malignancy [http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm257670.htm]
ARBS’s Do Not Increase the Risk of Myocardial Infarction [MEDLINE]

References

Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med. 2007;167(18):1930 [MEDLINE]
Risk of angioedema with angiotensin receptor blockers in patients with prior angioedema associated with angiotensin-converting enzyme inhibitors: a meta-analysis. Ann Allergy Asthma Immunol. 2008 Nov;101(5):495-9. doi: 10.1016/S1081-1206(10)60288-8 [MEDLINE]
Potential of antihypertensive drugs for the prevention and treatment of Alzheimer’s disease. Expert Review of Neurotherapeutics 8 (9): 1286. September 2008. doi:10.1586/14737175.8.9.1285
ONTARGET Investigators: Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547 [MEDLINE]
Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet. 2008;372(9638):547 [MEDLINE]
Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ 2010; 340 (9): b5465. doi:10.1136/bmj.b5465 [MEDLINE]
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm257670.htm
Angiotensin receptor blockers and risk of myocardial infarction: meta-analyses and trial sequential analyses of 147 020 patients from randomised trials. BMJ. 2011;342:d2234 [MEDLINE]
Effects of telmisartan, irbesartan, valsartan, candesartan, and losartan on cancers in 15 trials enrolling 138,769 individuals. J Hypertens. 2011;29(4):623 [MEDLINE]