Elsartan

Elsartan 10 mg Tablet: Each tablet contains 10 mg of Elsartan.

Elsartan 20 mg Tablet: Each tablet contains 20 mg of Elsartan.

Elsartan 40 mg Tablet: Each tablet contains 40 mg of Elsartan.

Elsartan (Elsartan), a prodrug, which is hydrolysed to the active metabolite Elsartan during absorption from the gastrointestinal tract. Elsartan is a selective AT₁ subtype angiotensin II receptor antagonist.

Elsartan is described chemically as (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylate. Alternatively, it can be described as 2,3-dihydroxy-2-butenyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonate.

Its empirical formula is C₂₉H₃₀N₆O₆.

Elsartan is a white to light yellowish-white powder or crystalline powder with a molecular weight of 558.59. It is practically insoluble in water and sparingly soluble in methanol.

Elsartan is indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs. There are no controlled trials demonstrating risk reduction with Elsartan.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

It may be used alone or in combination with other antihypertensive agents.

Elsartan is used alone or together with other medicines to treat high blood pressure (hypertension). High blood pressure adds to the workload of the heart and arteries. If it continues for a long time, the heart and arteries may not function properly. This can damage the blood vessels of the brain, heart, and kidneys, resulting in a stroke, heart failure, or kidney failure. Lowering blood pressure can reduce the risk of strokes and heart attacks.

Elsartan is an angiotensin II receptor blocker (ARB). It works by blocking a substance in the body that causes the blood vessels to tighten. As a result, Elsartan relaxes the blood vessels. This lowers blood pressure and increases the supply of blood and oxygen to the heart.

Elsartan is available only with your doctor's prescription.

Adult Hypertension

Dosage must be individualized. The usual recommended starting dose of Elsartan is 20 mg once daily when used as monotherapy in patients who are not volume-contracted. For patients requiring further reduction in blood pressure after 2 weeks of therapy, the dose of Elsartan may be increased to 40 mg. Doses above 40 mg do not appear to have greater effect. Twice-daily dosing offers no advantage over the same total dose given once daily.

No initial dosage adjustment is recommended for elderly patients, for patients with moderate to marked renal impairment (creatinine clearance <40 mL/min) or with moderate to marked hepatic dysfunction. For patients with possible depletion of intravascular volume (e.g., patients treated with diuretics, particularly those with impaired renal function), initiate Elsartan under close medical supervision and give consideration to use of a lower starting dose.

Elsartan may be administered with or without food.

If blood pressure is not controlled by Elsartan alone, a diuretic may be added. Elsartan may be administered with other antihypertensive agents.

Pediatric Hypertension (6 to 16 years of age)

Dosage must be individualized. For children who can swallow tablets, the usual recommended starting dose of Elsartan is 10 mg once daily for patients who weigh 20 to <35 kg (44 to 77 lb), or 20 mg once daily for patients who weigh ≥35 kg. For patients requiring further reduction in blood pressure after 2 weeks of therapy, the dose of Elsartan may be increased to a maximum of 20 mg once daily for patients who weigh <35 kg or 40 mg once daily for patients who weigh ≥35 kg.

Children <1 year of age must not receive Elsartan for hypertension.

For children who cannot swallow tablets, the same dose can be given using an extemporaneous suspension as described below. Follow the suspension preparation instructions below to administer Elsartan as a suspension.

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

Add 50 mL of Purified Water to an amber polyethylene terephthalate (PET) bottle containing twenty Elsartan 20 mg tablets and allow to stand for a minimum of 5 minutes. Shake the container for at least 1 minute and allow the suspension to stand for at least 1 minute. Repeat 1-minute shaking and 1-minute standing for four additional times. Add 100 mL of Ora-Sweet®* and 50 mL of Ora-Plus®* to the suspension and shake well for at least 1 minute. 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.

* Ora-Sweet® and Ora-Plus® are registered trademarks of Paddock Laboratories, Inc.

See also:
What is the most important information I should know about Elsartan?

Hypersensitivity to Elsartan or to any of the excipients of Elsartan.

Biliary obstruction.

Do not co-administer aliskiren with Elsartan in patients with diabetes.

Use in pregnancy: There is no experience with the use of Elsartan in pregnant women. However, drugs that act directly on the renin-angiotensin system administered during the 2nd and 3rd trimesters of pregnancy have been reported to cause foetal and neonatal injury (hypotension, renal dysfunction, oliguria and/or anuria, oligohydramnios, skull hypoplasia, intrauterine growth retardation, lung hypoplasia, facial abnormalities, limb contracture) and even death.

Thus, as for any drug in this class, Elsartan is contraindicated during the 2nd and 3rd trimesters of pregnancy. In addition, Elsartan must not be used during the 1st trimester. If pregnancy occurs during therapy, Elsartan must be discontinued as soon as possible.

Use in lactation: Elsartan is excreted in the milk of lactating rats, but it is not known whether Elsartan is excreted in human milk. Mothers must not breastfeed if they are taking Elsartan.

Use Elsartan as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Take Elsartan by mouth with or without food.
• If you cannot swallow tablets, ask your doctor or pharmacist about preparing a suspension of Elsartan.
• If you also take colesevelam, take it at least 4 hours after you take Elsartan.
• Take Elsartan on a regular schedule to get the most benefit from it. Taking Elsartan at the same time each day will help you remember to take it.
• Continue to take Elsartan even if you feel well. Do not miss any doses.
• If you miss a dose of Elsartan, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Elsartan.

Elsartan is used to treat high blood pressure (hypertension), prevention and treatment of heart attack (Myocardial Infarction) and heart failure; when heart is unable to pump sufficient blood. It is also used in patients of diabetes with kidney failure.

See also:
What other drugs will affect Elsartan?

Elsartan

No significant drug interactions were reported in studies in which Elsartan was co-administered with hydrochlorothiazide, digoxin or warfarin in healthy volunteers. The bioavailability of Elsartan was not significantly altered by the co-administration of antacids [Al(OH)3/Mg(OH)2]. Elsartan is not metabolized by the cytochrome P450 system and has no effects on P450 enzymes; thus, interactions with drugs that inhibit, induce or are metabolized by those enzymes are not expected.

Hydrochlorothiazide

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

Alcohol, Barbiturates, Or Narcotics– potentiation of orthostatic hypotension may occur.

Antidiabetic Drugs (oral agents and insulin)– dosage adjustment of the antidiabetic drug may be required.

Other Antihypertensive Drugs– additive effect or potentiation.

Cholestyramine and Colestipol Resins– absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. Single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85 and 43 percent, respectively.

Corticosteroids, ACTH– intensified electrolyte depletion, particularly hypokalemia.

Pressor Amines (e.g. Norepinephrine)– possible decreased response to pressor amines but not sufficient to preclude their use.

Skeletal Muscle Relaxants, Non depolarizing (e.g. Tubocurarine)– possible increased responsiveness to the muscle relaxant.

Lithium– should not generally be given with diuretics. Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations before use of such preparation with Elsartan-hydrochlorothiazide.

Non-steroidal Anti-inflammatory Drugs– in some patients the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when Elsartan-hydrochlorothiazide tablets and non-steroidal anti-inflammatory agents are used concomitantly, the patients should be observed closely to determine if the desired effect of the diuretic is obtained

See also:
What are the possible side effects of Elsartan?

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.

Adult Hypertension

Elsartan has been evaluated for safety in more than 3825 patients/subjects, including more than 3275 patients treated for hypertension in controlled trials. This experience included about 900 patients treated for at least 6 months and more than 525 for at least 1 year. Treatment with Elsartan was well tolerated, with an incidence of adverse reactions similar to placebo. Events generally were mild, transient and had no relationship to the dose of Elsartan.

The overall frequency of adverse reactions was not dose-related. Analysis of gender, age and race groups demonstrated no differences between Elsartan and placebo-treated patients. The rate of withdrawals due to adverse reactions in all trials of hypertensive patients was 2.4% (i.e., 79/3278) of patients treated with Elsartan and 2.7% (i.e., 32/1179) of control patients. In placebo-controlled trials, the only adverse reaction that occurred in more than 1% of patients treated with Elsartan and at a higher incidence versus placebo was dizziness (3% vs. 1%).

The following adverse reactions occurred in placebo-controlled clinical trials at an incidence of more than 1% of patients treated with Elsartan, but also occurred at about the same or greater incidence in patients receiving placebo: back pain, bronchitis, creatine phosphokinase increased, diarrhea, headache, hematuria, hyperglycemia, hypertriglyceridemia, influenza-like symptoms, pharyngitis, rhinitis and sinusitis.

The incidence of cough was similar in placebo (0.7%) and Elsartan (0.9%) patients.

Other potentially important adverse reactions that have been reported with an incidence of greater than 0.5%, whether or not attributed to treatment, in the more than 3100 hypertensive patients treated with Elsartan monotherapy in controlled or open-label trials are listed below.

Body as a Whole: chest pain, peripheral edema

Central and Peripheral Nervous System: vertigo

Gastrointestinal: abdominal pain, dyspepsia, gastroenteritis, nausea

Heart Rate and Rhythm Disorders: tachycardia

Metabolic and Nutritional Disorders: hypercholesterolemia, hyperlipemia, hyperuricemia

Musculoskeletal: arthralgia, arthritis, myalgia

Skin and Appendages: rash

Facial edema was reported in five patients receiving Elsartan. Angioedema has been reported with angiotensin II antagonists.

Laboratory Test Findings: In controlled clinical trials, clinically important changes in standard laboratory parameters were rarely associated with administration of Elsartan.

Hemoglobin and Hematocrit: Small decreases in hemoglobin and hematocrit (mean decreases of approximately 0.3 g/dL and 0.3 volume percent, respectively) were observed.

Liver Function Tests: Elevations of liver enzymes and/or serum bilirubin were observed infrequently. Five patients (0.1%) assigned to Elsartan and one patient (0.2%) assigned to placebo in clinical trials were withdrawn because of abnormal liver chemistries (transaminases or total bilirubin). Of the five Elsartan patients, three had elevated transaminases, which were attributed to alcohol use, and one had a single elevated bilirubin value, which normalized while treatment continued.

Pediatric Hypertension

No relevant differences were identified between the adverse experience profile for pediatric patients aged 1 to 16 years and that previously reported for adult patients.

Post-Marketing Experience

The following adverse reactions have been reported in post-marketing experience. 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, angioedema, anaphylactic reactions

Gastrointestinal: Vomiting, sprue-like enteropathy

Metabolic and Nutritional Disorders: Hyperkalemia

Musculoskeletal: Rhabdomyolysis

Urogenital System: Acute renal failure, increased blood creatinine levels

Skin and Appendages: Alopecia, pruritus, urticaria

Data from one controlled trial and an epidemiologic study have suggested that high-dose Elsartan may increase cardiovascular (CV) risk in diabetic patients, but the overall data are not conclusive. The randomized, placebo-controlled, double-blind ROADMAP trial (Randomized Elsartan And Diabetes MicroAlbuminuria Prevention trial, n=4447) examined the use of Elsartan, 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 Elsartan 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 Elsartan group compared to the placebo group (15 Elsartan vs. 3 placebo, HR 4.9, 95% confidence interval [CI], 1.4, 17), but the risk of non-fatal myocardial infarction was lower with Elsartan (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 Elsartan (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 Elsartan 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 Elsartan 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 Elsartan 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.