Benicar

— THERAPEUTIC CATEGORIES —
  • Hypertension
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Benicar Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Olmesartan medoxomil 5mg, 20mg, 40mg; tabs.

    Pharmacological Class

    Angiotensin II receptor blocker (ARB).

    How Supplied

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

    How Supplied

    Benicar is supplied as:

    • 5 mg yellow, round, film-coated, non-scored tablets debossed with Sankyo on one side and C12 on the other side
      • Bottles of 30
    • 20 mg white, round, film-coated, non-scored tablets debossed with Sankyo on one side and C14 on the other side
      • Bottles of 30, 90
      • Blisters of 1×30, 10×10, 6×30
    • 40 mg white, oval-shaped, film-coated, non-scored tablets debossed with Sankyo on one side and C15 on the other side
      • Bottles of 30, 90
      • Blisters of 1×30, 10×10, 6×30

    Storage

    Store at 20–25° C (68–77° F).

    Manufacturer

    Cosette Pharmaceuticals, Inc.

    Generic Availability

    YES

    Mechanism of Action

    Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle.

    Benicar Indications

    Indications

    Hypertension.

    Benicar Dosage and Administration

    Adult

    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

    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.

    Administration

    Preparation of Suspension (for 200mL of a 2mg/mL suspension)

    • Add 50mL of Purified Water to an amber polyethylene terephthalate (PET) bottle containing twenty Benicar 20mg tablets and allow to stand for a minimum of 5mins. 
    • Shake the container for at least 1min and allow the suspension to stand for at least 1min.
    • Repeat 1-min shaking and 1-min standing for 4 additional times. 
    • Add 100mL of ORA-Sweet® and 50mL of ORA-Plus®1 to the suspension and shake well for at least 1min. 
    • The suspension should be refrigerated at 2–8° C (36–46° F) and can be stored for up to 4 weeks. 
    • Shake the suspension well before each use and return promptly to the refrigerator.

    Benicar Contraindications

    Contraindications

    Concomitant aliskiren in patients with diabetes.

    Benicar Boxed Warnings

    Boxed Warning

    Fetal toxicity.

    Benicar Warnings/Precautions

    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.

    Warnings/Precautions

    Fetal Toxicity 

    • Benicar can cause fetal harm when given to a pregnant woman. 
    • Use of drugs that act on the renin-angiotensin system (RAS) during the 2nd and 3rd trimesters of pregnancy reduces fetal renal function and increases fetal/neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. 
    • Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. 
    • When pregnancy is detected, discontinue Benicar as soon as possible.

    Morbidity in Infants 

    • Use of Benicar in children <1 year of age is not recommended. 
    • Drugs that act directly on the renin-angiotensin-aldosterone system (RAAS) can have effects on the development of immature kidneys.

    Hypotension in Volume- or Salt-Depleted Patients 

    • In patients with an activated renin-angiotensin-aldosterone system, such as volume- and/or salt-depleted patients (eg, being treated with high doses of diuretics), symptomatic hypotension may occur after starting treatment with Benicar. 
    • Initiate treatment under close medical supervision; consider starting at a lower dose. 
    • If hypotension does occur, place the patient in the supine position and, if necessary, give an IV infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, and can usually be continued without difficulty once the blood pressure has stabilized. 

    Impaired Renal Function 

    • Inhibiting the renin-angiotensin-aldosterone system (RAAS) can decrease renal function in susceptible individuals treated with Benicar. 
    • In patients whose renal function may depend upon the activity of the renin-angiotensin-aldosterone system (eg, those with severe CHF), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and, rarely, with acute renal failure and/or death; similar results may occur in those treated with Benicar.
    • In patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported from studies of ACE inhibitors.

    Sprue-like Enteropathy

    • Severe, chronic diarrhea with substantial weight loss has been reported in patients taking olmesartan months to years after drug initiation. 
    • Intestinal biopsies of patients often demonstrated villous atrophy. 
    • If a patient develops these symptoms during olmesartan treatment, exclude other etiologies.
    • Consider alternative antihypertensive therapy in cases where no other etiology is identified.

    Hyperkalemia

    • Serum potassium should be monitored in patients receiving Benicar. 
    • Drugs that inhibit the renin angiotensin system can cause hyperkalemia. 
    • Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of K+-sparing diuretics, K+ supplements and/or K+-containing salt substitutes.

    Pregnancy Considerations

    Benicar can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the 2nd and 3rd trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. 

    When pregnancy is detected, discontinue Benicar as soon as possible. Consider alternative antihypertensive therapy during pregnancy.

    Nursing Mother Considerations

    There is no information regarding the presence of olmesartan in human milk, the effects on the breastfed infant, or the effects on milk production. 

    Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

    Pediatric Considerations

    Benicar was generally well tolerated in pediatric patients, and the adverse experience profile was similar to that described for adults. Benicar has not been shown to be effective for hypertension in children <6 years of age.

    Use of Benicar in children <1 year of age is not recommended.

    Geriatric Considerations

    No overall differences in effectiveness or safety were observed between elderly patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

    Renal Impairment Considerations

    No initial dosage adjustment is recommended for patients with moderate to marked renal impairment (CrCl <40mL/min).

    Hepatic Impairment Considerations

    No initial dosage adjustment is recommended for patients with moderate to marked hepatic dysfunction.

    Other Considerations for Specific Populations

    The antihypertensive effect of Benicar 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 Pharmacokinetics

    Absorption

    Olmesartan medoxomil is rapidly and completely bioactivated by ester hydrolysis to olmesartan during absorption from the GI tract.
    The absolute bioavailability of olmesartan is ~26%.

    After oral administration, the peak plasma concentration (Cmax) of olmesartan is reached after 1–2 hours. Food does not affect the bioavailability of olmesartan.

    Distribution

    Volume of distribution: ~17 L. Plasma protein bound: 99%; does not penetrate red blood cells.

    Metabolism

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

    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.

    Benicar Interactions

    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.

    Benicar Adverse Reactions

    Adverse Reactions

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

    Benicar Clinical Trials

    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).

    Benicar Note

    Not Applicable

    Benicar Patient Counseling

    Patient Counseling

    Pregnancy 

    • Advise female patients of childbearing age about the consequences of exposure to Benicar during pregnancy. Discuss treatment options with women planning to become pregnant.
    • Tell patients to report pregnancies to their physicians as soon as possible.

    Lactation 

    • Advise nursing women not to breastfeed during treatment with Benicar.

    Hyperkalemia

    • Advise patients not to use K+ supplements or salt substitutes that contain K+ without consulting their healthcare provider.

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