Benicar HCT

Benicar HCT is a prescription medication used to treat high blood pressure. Benicar HCT is a single product containing 2 medications: olmesartan and hydrochlorothiazide. Olmesartan is in a class of medications called angiotensin II receptor antagonists. It works by blocking the action of certain natural substances that tighten the blood vessels, allowing the blood to flow more smoothly and the heart to pump more efficiently. Hydrochlorothiazide belongs to a group of drugs called thiazide diuretics, which work by stopping reabsorption of salt into your body. This prevents fluid from building up in the body.

This medication comes in tablet form. It is taken once daily, with or without food.

Common side effects include nausea, a condition of excess of uric acid in the blood (hyperuricemia), dizziness, and an infection that affects the nose, throat, and airways (upper respiratory tract infection).

Serious side effects have been reported with Benicar HCT. See the "Benicar HCT Precautions" section. 

Common side effects of Benicar HCT include the following:

• nausea
• a condition of excess of uric acid in the blood (hyperuricemia)
• dizziness
• an infection that affects the nose, throat, and airways (upper respiratory tract infection)

This is not a complete list of Benicar HCT side effects. Ask your doctor or pharmacist for more information. 

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. 

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Benicar HCT falls into category D. When pregnancy is detected, discontinue Benicar HCT as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the unborn baby.

Do not use if you are pregnant. If you become pregnant, stop taking this medicine and tell your doctor right away.

You should not use this medicine if you are unable to urinate.

If you have diabetes, do not use hydrochlorothiazide and olmesartan together with any medication that contains aliskiren (such as Tekturna or Tekamlo).

You should not use this medicine if you are allergic to hydrochlorothiazide or olmesartan, if you are unable to urinate.

If you have diabetes, do not use hydrochlorothiazide and olmesartan together with any medication that contains aliskiren (such as Tekturna or Tekamlo).

You may also need to avoid taking hydrochlorothiazide and olmesartan with aliskiren if you have kidney disease.

To make sure hydrochlorothiazide and olmesartan is safe for you, tell your doctor if you have ever had:

• kidney disease;

• liver disease;

• congestive heart failure;

• glaucoma;

• low or high levels of potassium in your blood;

• asthma or allergies;

• high cholesterol or triglyceride levels;

• gout;

• lupus;

• diabetes; or

• an allergy to penicillin or sulfa drugs.

Do not use if you are pregnant. If you become pregnant, stop taking this medicine and tell your doctor right away. Hydrochlorothiazide and olmesartan can cause injury or death to the unborn baby if you take the medicine during your second or third trimester.

Hydrochlorothiazide can pass into breast milk and may cause side effects in the nursing baby. You should not breast-feed while using this medicine.

Take this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

Take this medicine with or without food.

If you are also using colesevelam (Welchol®), take it at least 4 hours after taking Benicar HCT®.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For high blood pressure:
    • Adults—One tablet once a day. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food.
• Keep taking Benicar HCT as you have been told by your doctor or other health care provider, even if you feel well.
• To gain the most benefit, do not miss doses.
• This medicine may cause you to pass urine more often. To keep from having sleep problems, try to take before 6 pm.
• Take this medicine at the same time of day.
• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

The following adverse reactions with Benicar HCT are described elsewhere:

• Hypotension in Volume- or Salt-Depleted Patients [see Warnings and Precautions (5.2)]
• Impaired Renal Function [see Warnings and Precautions (5.3)]
• Hypersensitivity Reactions [see Warnings and Precautions (5.4)]
• Electrolyte and Metabolic Imbalances [see Warnings and Precautions (5.5)]
• Acute Myopia and Secondary Angle-Closure Glaucoma [see Warnings and Precautions (5.6)]
• Systemic Lupus Erythematosus [see Warnings and Precautions (5.7)]
• Sprue-Like Enteropathy [see Warnings and Precautions (5.8)]

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Olmesartan medoxomil and hydrochlorothiazide

The concomitant use of olmesartan medoxomil and hydrochlorothiazide was evaluated for safety in 1243 hypertensive patients. Treatment with olmesartan medoxomil and hydrochlorothiazide was well tolerated, with an incidence of adverse events similar to that of placebo. Adverse reactions were generally mild, transient and not dependent on the dose of olmesartan medoxomil and hydrochlorothiazide.

The rate of withdrawals for adverse events in all trials of hypertensive patients was 2.0% (25/1243) on olmesartan medoxomil plus hydrochlorothiazide and 2.0% (7/342) on placebo.

In a placebo-controlled, factorial clinical trial of olmesartan medoxomil (2.5 mg to 40 mg) and hydrochlorothiazide (12.5 mg to 25 mg), the following adverse reactions reported in Table 1 occurred in >2% of patients, and more often on the olmesartan medoxomil and hydrochlorothiazide combination than on placebo.

Other adverse reactions that have been reported with an incidence of greater than 1.0%, whether or not attributed to treatment, in the more than 1200 hypertensive patients treated with olmesartan medoxomil and hydrochlorothiazide in controlled or open-label trials are listed below.

Body as a Whole: chest pain, back pain, peripheral edema
Central and Peripheral Nervous System: vertigo
Gastrointestinal: abdominal pain, dyspepsia, gastroenteritis, diarrhea
Liver and Biliary System: SGOT increased, GGT increased, ALT increased
Metabolic and Nutritional: creatine phosphokinase increased
Musculoskeletal: arthritis, arthralgia, myalgia
Respiratory System: coughing
Skin and Appendages Disorders: rash
Urinary System: hematuria

Facial edema was reported in 2/1243 patients receiving olmesartan medoxomil and hydrochlorothiazide. Angioedema has been reported with angiotensin II receptor antagonists, including Benicar HCT.

Hydrochlorothiazide

Other adverse reactions that have been reported with hydrochlorothiazide are listed below:

Body as a Whole: weakness
Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation
Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia
Hypersensitivity: purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions
Metabolic: glycosuria, hyperuricemia
Musculoskeletal: muscle spasm
Nervous System/Psychiatric: restlessness
Renal: renal dysfunction, interstitial nephritis
Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis
Special Senses: transient blurred vision, xanthopsia

Clinical Laboratory Test Findings

Creatinine/blood urea nitrogen (BUN): Minor elevations in creatinine and BUN occurred in 1.7% and 2.5% respectively, of patients taking Benicar HCT and 0% and 0% respectively, given placebo in controlled clinical trials.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Benicar HCT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Body as a Whole: Asthenia
Gastrointestinal: Vomiting
Metabolic: Hyperkalemia
Musculoskeletal: Rhabdomyolysis
Skin and Appendages: Alopecia, pruritus

Data from one controlled trial and an epidemiologic study have suggested that high-dose olmesartan may increase cardiovascular (CV) risk in diabetic patients, but the overall data are not conclusive. The randomized, placebo-controlled, double-blind ROADMAP trial (Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention trial, n=4447) examined the use of olmesartan, 40 mg daily, vs. placebo in patients with type 2 diabetes mellitus, normoalbuminuria, and at least one additional risk factor for CV disease. The trial met its primary endpoint, delayed onset of microalbuminuria, but olmesartan had no beneficial effect on decline in glomerular filtration rate (GFR). There was a finding of increased CV mortality (adjudicated sudden cardiac death, fatal myocardial infarction, fatal stroke, revascularization death) in the olmesartan group compared to the placebo group (15 olmesartan vs. 3 placebo, HR 4.9, 95% confidence interval [CI], 1.4, 17), but the risk of non-fatal myocardial infarction was lower with olmesartan (HR 0.64, 95% CI 0.35, 1.18).

The epidemiologic study included patients 65 years and older with overall exposure of > 300,000 patient-years. In the sub-group of diabetic patients receiving high-dose olmesartan (40 mg/d) for > 6 months, there appeared to be an increased risk of death (HR 2.0, 95% CI 1.1, 3.8) compared to similar patients taking other angiotensin receptor blockers. In contrast, high-dose olmesartan use in non-diabetic patients appeared to be associated with a decreased risk of death (HR 0.46, 95% CI 0.24, 0.86) compared to similar patients taking other angiotensin receptor blockers. No differences were observed between the groups receiving lower doses of olmesartan compared to other angiotensin blockers or those receiving therapy for < 6 months.

Overall, these data raise a concern of a possible increased CV risk associated with the use of high-dose olmesartan in diabetic patients. There are, however, concerns with the credibility of the finding of increased CV risk, notably the observation in the large epidemiologic study for a survival benefit in non-diabetics of a magnitude similar to the adverse finding in diabetics.

Agents Increasing Serum Potassium

Coadministration of Benicar HCT with other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

Lithium

Increases in serum lithium concentrations and lithium toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists or hydrochlorothiazide. Monitor serum lithium levels during concomitant use.

Non-Steroidal Anti-Inflammatory Agents including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)

Olmesartan medoxomil

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists (including olmesartan medoxomil) may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving olmesartan medoxomil and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including olmesartan medoxomil may be attenuated by NSAIDs including selective COX-2 inhibitors.

Hydrochlorothiazide

In some patients the administration of a NSAID can reduce the diuretic, natriuretic, and antihypertensive effects of thiazide diuretics. Therefore, monitor blood pressure closely.

Dual Blockade of the Renin Angiotensin System

Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Most patients receiving the combination of two RAS inhibitors do not obtain any additional benefit compared to monotherapy. In general, avoid combined use of RAS inhibitors. Closely monitor blood pressure, renal function and electrolytes in patients on Benicar HCT and other agents that affect the RAS.

Do not co-administer aliskiren with Benicar HCT in patients with diabetes [see Contraindications (4)]. Avoid use of aliskiren with Benicar HCT in patients with renal impairment (GFR <60 ml/min).

Colesevelam Hydrochloride

Concurrent administration of bile acid sequestering agent colesevelam hydrochloride reduces the systemic exposure and peak plasma concentration of olmesartan. Administration of olmesartan at least 4 hours prior to colesevelam hydrochloride decreased the drug interaction effect. Consider administering olmesartan at least 4 hours before the colesevelam hydrochloride dose [see Clinical Pharmacology (12.3)].

Use of Hydrochlorothiazide with Other Drugs

When administered concurrently the following drugs may interact with thiazide diuretics:

Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.

Ion exchange resins: Staggering the dosage of hydrochlorothiazide and ion exchange resins (e.g., cholestyramine, colestipol) such that hydrochlorothiazide is administered at least 4 hours before or 4 – 6 hours after the administration of resins would potentially minimize the interaction [see Clinical Pharmacology (12.3)].

Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia.

Benicar HCT is supplied as follows:

Tablets are packaged as follows:

Storage

Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature].

Pregnancy: Advise female patients of childbearing age about the consequences of exposure to Benicar HCT during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible [see Use in Specific Populations (8.1)].

Symptomatic hypotension and syncope: Advise patients that lightheadedness can occur, especially during the first days of therapy, and to report this symptom to a healthcare provider. Inform patients that dehydration from inadequate fluid intake, excessive perspiration, vomiting, or diarrhea may lead to an excessive fall in blood pressure. If syncope occurs advise patients, to contact their healthcare provider.

Potassium Supplements: Advise patients not to use potassium supplements or salt substitutes containing potassium without consulting their healthcare provider.

Acute myopia and secondary angle-closure glaucoma: Advise patients to discontinue Benicar HCT and seek immediate medical attention if they experience symptoms of acute myopia or secondary angle-closure glaucoma [see Warnings and Precautions (5.6)].

Manufactured for Daiichi Sankyo, Inc., Parsippany, New Jersey 07054

Copyright © Daiichi Sankyo, Inc. 2016. All rights reserved.

AU: Use is contraindicated. UK: Use is not recommended during the first trimester of pregnancy and is contraindicated during the second and third trimesters. US: This drug should not be used during pregnancy unless there are no alternatives and the benefit outweighs the risk to the fetus. AU TGA pregnancy category: D US FDA pregnancy category: D Comments: Adequate methods of contraception should be encouraged.

Animal studies have revealed evidence of fetal toxicity. Neonatal thrombocytopenia or fetal or neonatal jaundice have been reported with maternal thiazide therapy. In humans, use of drugs that act on the renin angiotensin system (RAS) during the second and third trimesters increases fetal and neonatal morbidity and death. There are no controlled data in human pregnancy. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.