Hypertension:

Indications for: BENICAR

Hypertension.

Clinical Trials:

Adult Hypertension

  • The efficacy of Benicar was demonstrated in 7 placebo-controlled studies at doses ranging from 2.5mg to 80mg for 6–12 weeks, each showing statistically significant reductions in peak and trough blood pressure. 
  • A total of 2693 patients (2145 Benicar; 548 placebo) with essential hypertension were studied.

Benicar once daily lowered diastolic and systolic blood pressure, in which the response was dose related, as shown (see full labeling for graph). A Benicar 20mg daily dose produces a trough sitting blood pressure (BP) reduction over placebo of about 10/6 mmHg; while a 40mg daily dose produces a trough sitting BP reduction of about 12/7 mmHg. Benicar doses >40mg had little additional effect. The onset of the antihypertensive effect occurred within 1 week and was largely manifest after 2 weeks.

The blood pressure lowering effect was maintained throughout the 24-hour period with Benicar once daily, with trough-to-peak ratios for systolic and diastolic response between 60 and 80%.

The blood pressure lowering effect of Benicar, with/without hydrochlorothiazide, was maintained in patients treated for up to 1 year. There was no evidence of tachyphylaxis during long-term treatment with Benicar or rebound effect following abrupt withdrawal of olmesartan medoxomil after 1 year of treatment.

The antihypertensive effect of Benicar was similar in men and women and in patients older and younger than 65 years. The effect was smaller in black patients (usually a low-renin population), as has been seen with ACE inhibitors, beta-blockers and other angiotensin receptor blockers. Benicar had an additional blood pressure lowering effect when added to hydrochlorothiazide.

Pediatric Hypertension

  • The efficacy of Benicar in the pediatric population was evaluated in a randomized, double-blind study involving 302 hypertensive patients aged 6–16 years. 
  • Study population consisted of an all-black cohort of 112 patients and a mixed racial cohort of 190 patients, including 38 black patients. 
  • The etiology of the hypertension was predominantly essential hypertension (87% of the black cohort; 67% of the mixed cohort). 
  • Patients who weighed 20 to <35kg were randomized to 2.5 or 20mg of Benicar once daily; those who weighed ≥35kg were randomized to 5 or 40mg of Benicar once daily. 
  • At the end of 3 weeks, patients were re-randomized to continuing Benicar or to taking placebo for up to 2 weeks. 

During the initial dose-response phase, Benicar significantly reduced both systolic and diastolic blood pressure in a weight-adjusted, dose-dependent manner. Overall, the two dose levels of Benicar (low and high) significantly reduced systolic blood pressure by 6.6 and 11.9 mmHg from the baseline, respectively. These reductions in systolic blood pressure included both drug and placebo effect.

During the randomized withdrawal to placebo phase, mean systolic blood pressure at trough was 3.2 mmHg lower and mean diastolic blood pressure at trough was 2.8 mmHg lower in patients continuing Benicar versus those withdrawn to placebo. These differences were statistically different. As observed in adult populations, the blood pressure reductions were smaller in black patients.

In the same study, 59 patients aged 1–5 years who weighed ≥5 kg received 0.3mg/kg of Benicar once daily for 3 weeks in an open-label phase and then were randomized to receiving Benicar or placebo in a double-blind phase. At the end of the second week of withdrawal, the mean systolic/diastolic blood pressure at trough was 3/3 mmHg lower in the group randomized to Benicar; this difference in blood pressure was not statistically significant (95% CI, -2 to 7/-1 to 7).

Adult Dosage:

Individualize. ≥16yrs: Monotherapy, not volume-depleted: initially 20mg once daily; may increase to max 40mg once daily after 2 weeks. Volume-depleted (eg, concomitant diuretic): consider lower initial dose.

Children Dosage:

Individualize. <6yrs: not recommended. 6–16yrs: (20kg to <35kg): initially 10mg once daily; may increase to max 20mg once daily after 2 weeks; (≥35kg): initially 20mg once daily; may increase to max 40mg once daily after 2 weeks. Tabs may be prepared as an oral suspension if unable to swallow: see full labeling.

BENICAR Contraindications:

Concomitant aliskiren in patients with diabetes.

Boxed Warning:

Fetal toxicity.

BENICAR Warnings/Precautions:

Fetal toxicity may develop; discontinue if pregnancy is detected. Correct salt/volume depletion before initiating therapy, or monitor closely. Renal impairment: monitor for worsening renal function. Severe CHF. Renal artery stenosis. Monitor serum potassium. Possibly less effective in black patients. Elderly. Neonates. Pregnancy: monitor. Nursing mothers: not recommended.

BENICAR Classification:

Angiotensin II receptor blocker (ARB).

BENICAR Interactions:

See Contraindications. Concomitant K+-sparing diuretics, K+ supplements, K+-containing salt substitutes may cause hyperkalemia. May be antagonized by, and renal toxicity potentiated by NSAIDs, including selective COX-2 inhibitors; monitor renal function periodically in elderly and/or volume-depleted. Dual inhibition of the renin-angiotensin system with ARBs, ACEIs or aliskiren may increase risk of hypotension, hyperkalemia, renal function changes; monitor closely. Avoid concomitant aliskiren in renal impairment (CrCl <60mL/min). Take at least 4hrs before colesevelam HCl dose. May increase lithium levels; monitor.

Adverse Reactions:

Dizziness, possible sprue-like enteropathy, renal dysfunction, hyperkalemia, rhabdomyolysis (rare).

Metabolism:

Following the rapid and complete conversion of olmesartan medoxomil to olmesartan during absorption, there is virtually no further metabolism of olmesartan. 

Drug Elimination:

Total plasma clearance of olmesartan is 1.3 L/h, with a renal clearance of 0.6 L/h. 

Renal (~35–50%), fecal via the bile (remainder). Half-life: ~13 hours.

Generic Drug Availability:

YES

How Supplied:

Tabs 5mg—30; 20mg, 40mg—30, 90, 1×30, 10×10, 6×30