American College of Cardiology/American Heart Association (ACC/AHA) guidelines for treatment of hypertension were last published in 2018. Treatment of hypertensive urgencies and emergencies is not discussed here.

Drugs available for treatment of chronic hypertension and their dosages, adverse effects, and costs are listed in the tables. Treatment of hypertensive urgencies and emergencies is not discussed here.

A reader asked whether healthcare providers should avoid prescribing the angiotensin receptor blocker (ARB) olmesartan medoxomil (Benicar, and others) because it can cause severe GI adverse effects.

In 2013, the FDA warned that olmesartan can cause sprue-like enteropathy, a condition characterized by intestinal villous atrophy, severe chronic diarrhea, and significant unintended weight loss. The warning was based on 23 cases of serious sprue-like enteropathy associated with use of olmesartan, some occurring years after starting the drug. All patients improved after stopping olmesartan; 10 had a positive rechallenge.1 A case series describing 22 patients reported similar observations.2

Duodenal biopsies in patients with olmesartan-associated enteropathy have shown elevated CD8+ T cell counts and overexpression of interleukin-15 by epithelial cells, biomarkers similar to those seen after gluten exposure in patients with celiac disease. Mucosal recovery and lower levels of inflammatory biomarkers were observed in biopsies obtained after stopping olmesartan.3

In an observational cohort study including about 4.5 million patients in France who started ARB or angiotensin converting enzyme (ACE) inhibitor therapy over a 6-year period, exposure to olmesartan for >2 years was associated with one additional hospitalization for intestinal malabsorption per 12,550 patients, compared with exposure to another ARB or ACE inhibitor; this difference was statistically significant.4

Isolated cases of enteropathy have been reported with use of other ARBs.5-8

The absolute risk of sprue-like enteropathy with olmesartan is very low, and the effect is reversible. Patients without GI risk factors whose hypertension is well controlled on olmesartan could probably continue taking it. For patients starting antihypertensive therapy and those with GI risk factors, any of the several other ACE inhibitors or ARBs available generically9 might be a better choice. Patients taking any ARB should notify their healthcare provider if they develop severe diarrhea.

1. FDA Drug Safety Communication: FDA approves label changes to include intestinal problems (sprue-like enteropathy) linked to blood pressure medicine olmesartan medoxomil. Available at: www.fda.gov. Accessed January 18, 2018.
2. A Rubio-Tapia et al. Severe spruelike enteropathy associated with olmesartan. Mayo Clin Proc 2012; 87:732.
3. EV Marietta et al. Immunopathogenesis of olmesartan-associated enteropathy. Aliment Pharmacol Ther 2015; 42:1303.
4. M Basson et al. Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study. Gut 2016; 65:1664.
5. A Negro et al. A case of moderate sprue-like enteropathy associated with telmisartan. J Clin Med Res 2017; 9:1022.
6. HS Mandavdhare et al. Telmisartan-induced sprue-like enteropathy: a case report and a review of patients using non-olmesartan angiotensin receptor blockers. Intest Res 2017; 15:419.
7. ML Herman et al. A case of severe sprue-like enteropathy associated with valsartan. ACG Case Rep J 2015; 2:92.
8. EY Choi and BJ McKenna. Olmesartan-associated enteropathy: a review of clinical and histologic findings. Arch Pathol Lab Med 2015; 139:1242.
9. Drugs for hypertension. Med Lett Drugs Ther 2017; 59:41.

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in the US and their dosages, adverse effects, and costs are listed in the tables. Treatment of hypertensive urgencies and emergencies is not discussed here.

The FDA has approved Byvalson (Allergan), a fixed-dose combination of the beta blocker nebivolol (Bystolic) and the angiotensin receptor blocker (ARB) valsartan (Diovan, and generics), for treatment of hypertension. It is the only combination product that contains nebivolol, and the first to combine a beta blocker with an ARB.

The FDA has approved Prestalia (Symplmed), an oral fixed-dose combination of the dihydropyridine calcium channel blocker amlodipine (Norvasc, and generics) and a new salt form of the angiotensin-converting enzyme (ACE) inhibitor perindopril, for treatment of hypertension in patients not adequately controlled on monotherapy or already taking both drugs, and in those just starting therapy who are likely to need multiple drugs to control their blood pressure. The new salt form (perindopril arginine) is more stable and has a longer shelf-life than perindopril erbumine (Aceon, and generics). Two other ACE inhibitor/calcium channel blocker combinations, benazepril/amlodipine (Lotrel, and generics) and trandolapril/verapamil ER (Tarka, and generics), have been available in the US for many years.

The FDA has approved a fixed-dose combination of the angiotensin receptor blocker (ARB) azilsartan and the thiazide-like diuretic chlorthalidone as Edarbyclor (Takeda) for treatment of hypertension

Drugs available in the US for treatment of chronic hypertension, with their dosages and adverse effects, are listed in the tables that begin on page 2. Combination products are listed on page 8. Drugs for treatment of hypertensive emergencies are not discussed here. They were reviewed previously.

The angiotensin receptor blocker (ARB) azilsartan medoxomil (Edarbi – Takeda) was recently approved by the FDA for oral treatment of hypertension, either alone or combined with other drugs. It is the eighth ARB approved for this indication.

The FDA has approved aliskiren/amlodipine/hydrochlorothiazide (Amturnide) for treatment of hypertension, with no restrictions except that it should not be used for initial therapy. A combination of the direct renin inhibitor aliskiren and the calcium channel blocker amlodipine (Tekamlo) was approved earlier for initial treatment.1

Use of combination tablets is, of course, more convenient than taking the components separately, and as long as all the same doses are available and the cost is no greater, there is no reason not to use them.

Aliskiren alone or in combination has not been shown to improve clinical outcomes.2 Whether it offers any advantage over the angiotensin receptor blockers (ARBs), which are also available in various antihypertensive combinations, remains to be determined.

1. Aliskiren/amlodipine (Tekamlo): another combination tablet for hypertension. Med Lett Drugs Ther 2010; 52:94.

2. Drugs for hypertension. Treat Guidel Med Lett 2009; 7:1.

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Many patients with hypertension require more than one drug to control their blood pressure. Tribenzor (Daiichi Sankyo), recently approved by the FDA for treatment of hypertension, combines the calcium channel blocker amlodipine (Norvasc, and others), the angiotensin receptor blocker (ARB) olmesartan (Benicar)and the most commonly prescribed diuretic, hydrochlorothiazide (HCTZ). Tribenzor is not approved for initial therapy, but is recommended for patients not adequately controlled on any 2-drug combination of a calcium channel blocker, an ARB or a diuretic.

The FDA has approved Twynsta (Boehringer Ingelheim), a fixed-dose combination of the calcium-channel blocker (CCB) amlodipine and the angiotensin receptor blocker (ARB) telmisartan, for treatment of hypertension.

Readers have asked us to update our 2004 article on tablet splitting. Breaking drug tablets in half is a common practice, but the FDA recently advised consumers against it (FDA Consumer Health Information, July 2009).

Drugs available in the US for treatment of chronic hypertension, with their dosages, adverse effects and costs, are listed in the tables that begin on page 2. Combination products are listed on page 9. Drugs for treatment of hypertensive emergencies are not discussed here. They were reviewed in Treatment Guidelines (volume 1, page 19, December 2002) and in The Medical Letter (volume 50, page 73, September 22, 2008).

The FDA has approved Exforge (Novartis) and Azor (Daiichi Sankyo), the first combinations of a calcium channel blocker (CCB) with an angiotensin receptor blocker (ARB) for treatment of hypertension. Amlodipine is the CCB in both products. The ARBs are valsartan in Exforge and olmesartan in Azor. All 3 of these drugs are available in fixed-dose combinations with other antihypertensive drugs.

Drugs available in the US for treatment of chronic hypertension, with their dosages, adverse effects and costs, are listed in the tables that begin on page 40. Combination products are listed on page 47. Drugs for treatment of hypertensive emergencies are not discussed here.

Angiotensin receptor blockers (ARBs) are widely used as an alternative to angiotensin converting enzyme (ACE) inhibitors for treatment of hypertension because they lower blood pressure without inducing a cough. It has not been established that they provide the same cardiac benefits as ACE inhibitors. Recently, an editorial in the British Medical Journal suggested that ARBs may increase the risk of myocardial infarction.

The importance of adequate control of hypertension in preventing organ damage and death is well established, but the choice of drugs is still controversial. Three recent drug trials, one supporting initial therapy with a diuretic, the second favoring an angiotensin converting enzyme (ACE) inhibitor, and the third showing equivalence between a calcium-channel blocker and an angiotensin-receptor blocker (ARB) have intensified the debate.

The choice of drugs for treatment of chronic heart failure continues to evolve. It has become increasingly recognized that drugs used in heart failure produce beneficial effects through neurohormonal as well as hemodynamic mechanisms. The treatment of decompensated heart failure is not discussed here; drugs used for this indication were reviewed in Cardiovascular Drugs in the ICU, Treatment Guidelines from The Medical Letter 2002; 1:19.

Drugs available in the US for treatment of chronic hypertension, with their dosages, adverse effects and costs, are listed in the table that begins on page 35. Combination products are listed on page 39. Drugs for treatment of hypertensive emergencies were discussed in Treatment Guidelines volume 1, issue 4, page 19, December 2002.

Olmesartan medoxomil (Benicar - Sankyo), a substituted imidazole, is the seventh oral angiotensin II receptor blocker (ARB) approved by the FDA for treatment of hypertension.