Eprosartan

Eprosartan is an antihypertensive agent belonging to Angiotensin II Receptor Blocker.

Eprosartan is approved for the treatment of Hypertension. It is also used to treat Diabetic Nephropathy and Congestive Heart Failure.

Following a single oral dose of Eprosartan of 300 mg, its absolute bioavailability is roughly 13%. After taking an oral dose of Eprosartan while fasting, plasma concentrations reach their peak 1 to 2 hours later. Eprosartan has a high (almost 98%) and consistent plasma protein binding across the concentration range achieved with therapeutic dosages. Eprosartan is primarily excreted as an unchanged metabolite by biliary and renal excretion. The amount of an oral dose that is recovered in the faeces and urine is 61% and 37%, respectively. Oral dose of <2% is eliminated in the urine as a glucuronide.

Eprosartan shows common side effects like swelling of the face, eyes, hands, throat, tongue, lips, lower legs or feet, ankles, hoarseness of voice, difficulty breathing or swallowing etc.

Eprosartan is available in the form of Tablet.

Eprosartan is available in India, EU, US, Canada, Australia, Switzerland, and Germany.

Eprosartan belonging to the Angiotensin II Receptor Blocker, acts as an antihypertensive agent. Eprosartan works by relaxing blood vessels so blood can flow more easily.

By blocking angiotensin II from binding to the AT1 receptor, which is present in many tissues, Eprosartan prevents the effects of angiotensin II that cause the body to secrete aldosterone and vasoconstrictors (e.g., vascular smooth muscle, adrenal gland). The AT2 receptor is also present in numerous organs, however it is unknown if it affects cardiovascular homeostasis. At the AT1 receptor, Eprosartan doesn't show any partial agonist action. It has a 1,000-fold higher affinity for the AT1 receptor than the AT2 receptor. Eprosartan is competitive and reversible inhibitor of the AT1 receptor, according to in vitro binding studies.

The onset of action of Eprosartan occurs within 1-2 hours of its administration.

The Duration of Action for Eprosartan in the body is approximately 24 hours.

The Tmax was found within 1-2 hours following the administration of Eprosartan and the Cmax was about 5 to 2000 ng/mL.

Eprosartan is available in the form of tablets.

Eprosartan comes as a tablet to take by mouth. Usually it is taken once or twice a day with or without food

Eprosartan is approved for the treatment of Hypertension. Eprosartan is used alone or in combination with other medicines. Lowering of high blood pressure helps prevent strokes, heart attacks, and kidney problems. This drug works by relaxing blood vessels so blood can flow more easily.

Eprosartan is an antihypertensive agent belonging to Angiotensin II Receptor Blocker. By selectively blocking angiotensin II from binding to the AT1 receptor in numerous tissues, Eprosartan inhibits the effects of angiotensin II that cause vasoconstriction and the release of aldosterone. Eprosartan is approved for the treatment of hypertension. Lowering of high blood pressure helps prevent strokes, heart attacks, and kidney problems.

Eprosartan is approved for use in the following clinical indications

• Hypertension

Eprosartan is indicated for the treatment of hypertension. Lowering of high blood pressure helps prevent strokes, heart attacks, and kidney problems. This drug works by relaxing blood vessels so blood can flow more easily. Eprosartan may be used alone or in combination with other antihypertensives such as diuretics and calcium channel blockers.

Although not approved, there have been certain off-label indications. These include:

• Diabetic Nephropathy

Eprosartan used as a first-line agent in the treatment of diabetic nephropathy.

• Congestive Heart Failure

Eprosartan used as a second-line agent in the treatment of congestive heart failure (only in those intolerant of ACE inhibitors).

• Hypertension

Recommends initial dose of 600 mg once daily as monotherapy in adults without intravascular volume depletion.

Usual dosage: Dose of 400–800 mg daily, given in 1 dose or 2 divided doses; limited experience with higher dosages. Some state 600–800 mg daily, given in 1 dose or 2 divided doses.

If effectiveness diminishes toward the end of dosing interval in patients treated once daily, consider increasing dosage or administering drug in two divided doses.

• Diabetic Nephropathy

A recommended medicine for managing patients with diabetes mellitus and persistent albuminuria who have urinary albumin excretion levels that are moderately elevated (30–300 mg/24 hours) or higher (>300 mg/24 hours); this medication slows the rate at which the renal disease progresses in these patients.

Eprosartan is available in various strengths as 400mg and 600mg.

Hypertension:

Potassium Rich Foods: Eprosartan may cause high blood potassium levels. Hence, avoid potassium-rich Food while taking this medication.

The dietary restriction should be individualized based on patient requirements.

Eprosartan is contraindicated in the following patients:

• Hypersensitivity
• Bilateral renal artery stenosis
• Do not coadminister with aliskiren in patients has diabetes
• Pregnancy

• Fetal Toxicity

Pregnancy Category D

In the second and third trimesters of pregnancy, taking medications that affect the renin-angiotensin system decreases foetal renal function and raises foetal and newborn morbidity and mortality. The resulting oligohydramnios can lead to skeletal abnormalities and hypoplastic foetal lungs. Skull hypoplasia, anuria, renal failure, hypotension and death are examples of potential newborn side effects. Eprosartan should be discontinued as soon as pregnancy is found. These undesirable effects are usually linked to using these medications throughout the second and third trimesters of pregnancy. In the majority of epidemiologic research assessing foetal anomalies following exposure to antihypertensive use in the first trimester, medications influencing the renin-angiotensin system have not been separated from other antihypertensive medicines. To ensure the better effect for both mother and foetus, maternal hypertension during pregnancy must be well managed.

Inform the mother about every potential risks to the foetus in the unlikely event that there is no suitable alternative to therapy with medications affecting the renin-angiotensin system for a specific patient. To evaluate the intra-amniotic environment, perform successive ultrasonography examinations. Eprosartan should be discontinued if oligohydramnios is found, unless the mother's life is in danger. Depending on the week of pregnancy, foetal testing may be necessary. However, patients and doctors should be aware that oligohydramnios might not develop until after the foetus has suffered irreparable harm. Infants who have experienced Eprosartan exposure in utero should be closely monitored for oliguria, hypotension, and hyperkalemia.

In pregnant rabbits given oral dosage as low as 10 mg Eprosartan/kg/day, it has been demonstrated that Eprosartan mesylate causes maternal and foetal toxicities (maternal and foetal mortality, poor maternal body weight and food consumption, resorptions, abortions, and litter loss). No maternal or fetal adverse effects were observed at 3 mg/kg/day; this oral dose yielded a systemic exposure (AUC) to unbound Eprosartan 0.8 times that achieved in humans given 400 mg twice a day. No adverse effects on in utero or postnatal development and offspring maturation were observed when Eprosartan mesylate was given to pregnant rats at oral doses up to 1000 mg Eprosartan/kg/day.

• Hypotension In Volume- And/or Salt-Depleted Patients

Symptomatic hypotension may happen in patients with an active renin-angiotensin system, such as those who are volume- and/or salt-depleted or receiving diuretic therapy. Eprosartan administration should either begin with the correction of these conditions or under under medical supervision. The patient should be treated in the supine position and, if necessary, given an intravenous infusion of normal saline if hypotension develops. A brief hypotensive reaction does not exclude ongoing therapy, which is usually easy to continue when the blood pressure has balanced.

Consumption of alcohol with Eprosartan can lower blood pressure resulting in drowsiness, dizziness or fainting; therefore, is better to avoid alcohol while taking Eprosartan.

Eprosartan is excreted in animal milk. Eprosartan may pass into human milk, however this is unknown. Considering that many medications are excreted in human milk and so that Eprosartan may produce major negative effects in nursing infants, a choice should be taken regarding whether to stop breastfeeding or to stop the medication, taking into account the significance of the drug to the mother.

Pregnancy Category C: (1st trimester); D (2nd and 3rd trimesters)

Avoid use in pregnancy. When pregnancy is detected, discontinue the use of Eprosartan as soon as possible. It acts directly on the renin-angiotensin system and can cause injury and death to the developing fetus.

The food warning while consuming Eprosartan is that it should be taken in concentrations during its consumption

Potassium Rich Foods: Eprosartan may cause high blood potassium levels. Hence, avoid potassium-rich Food while taking this medicine.

The adverse reactions related to Eprosartan can be categorized as

Common Adverse effects

• Fatigue
• Upper respiratory infection
• Cough
• Abdominal pain

Less Common Adverse effects

• Facial edema
• Dizziness
• Headache
• Neutropenia
• Back pain
• Muscle pain

• Dual Blockade of The Renin-Angiotensin System (RAS)

As compared to monotherapy, dual blockage of the RAS with ACE inhibitors, aliskiren, or angiotensin receptor blockers increases the risk of hypotension, hyperkalemia, and abnormalities in renal function (including acute renal failure). Most patients who receive two RAS inhibitors in combination do not benefit any more than they would with monotherapy. RAS inhibitors should not be used in combination. When patients are on Eprosartan or other RAS-affecting medications, closely monitor to their blood pressure, kidney function, and electrolytes.

Do not co-administer aliskiren with Eprosartan in patients with diabetes. Avoid use of aliskiren with Eprosartan in patients with renal impairment (GFR < 60 ml/min).

It has been demonstrated that Eprosartan has no impact on the pharmacodynamics of warfarin and glyburide as well as the pharmacokinetics of digoxin. As a result, no dosage modifications are required when using these medicines together. Inhibitors of the CYP450 enzyme would not be anticipated to affect the metabolism of Eprosartan because it is not metabolised by the cytochrome P450 system, and studies have shown that the CYP3A and 2C9-potent inhibitors ketoconazole and fluconazole have no effect on the pharmacokinetics of Eprosartan. Furthermore, ranitidine has no impact on the pharmacokinetics of Eprosartan.

Eprosartan (up to 400 mg twice a day or 800 mg every day) doses have been safely used with a thiazide diuretic hydrochlorothiazide. Eprosartan doses of up to 300 mg twice a day have been safely used simultaneously with sustained-release calcium channel blockers (sustained-release nifedipine) with no clinically significant adverse interactions.

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

The co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, such as Eprosartan, may worsen renal function in patients who are elderly, volume-depleted (including those receiving diuretic therapy), or who have compromised renal function. This could lead to acute renal failure. Usually, these effects are reversible. Patients using Eprosartan and NSAIDs should have their renal function routinely checked.

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

• Lithium

Lithium toxicity and serum lithium concentration increases have been observed when angiotensin II receptor agonists and lithium are administered concurrently. Monitor serum lithium levels during concomitant use.

The common side of Eprosartan include the following

Less common

• Burning or painful urination or changes in urinary frequency
• Cough
• Fever
• sore throat

Rare

• Dizziness, light headedness, or fainting
• swollen face, lips, limbs, or tongue

• Pregnancy

Pregnancy Category C (first trimester) and D (second and third trimesters):

Drugs that act directly on the renin-angiotensin system may cause fetal and neonatal morbidity and death when administered to the pregnant women. Several dozen cases have been reported in the world literature in patients who were taking angiotensin-converting enzyme inhibitors. When pregnancy is detected, Eprosartan should be discontinued as soon as possible. During the second and third trimesters of pregnancy, taking medications that directly affect the renin-angiotensin system has been related to foetal and neonatal harm, including hypotension, neonatal skull hypoplasia, anuria, reversible or permanent renal failure, and even death. There have also been reports of oligohydramnios, which is likely the outcome of diminished foetal renal function; in this situation, oligohydramnios has been linked to foetal limb contractures, craniofacial abnormalities, and hypoplastic lung development. Additionally documented conditions include prematurity, intrauterine growth restriction, and patent ductus arteriosus, though it is unclear whether these conditions were brought on by drug exposure. These negative side effects do not seem to be the result of first trimester-only intrauterine medication exposure. Mothers should be informed if their embryos and foetuses are only exposed to an angiotensin II receptor antagonist during the first trimester. However, doctors should advise their patients to stop taking Eprosartan as soon as possible once they learn they are pregnant. Rarely, possibly less frequently than once every thousand pregnancies, will there be no effective alternative to a medication that affects the renin-angiotensin system. In these unusual situations, the mothers should be informed of the possible risks to their fetuses, and repeated ultrasound tests should be done to evaluate the intra-amniotic environment.

If oligohydramnios is seen, Eprosartan should be stopped unless the mother's life is thought to be in danger. Depending on the week of pregnancy, contraction stress testing (CST), a nonstress test (NST), or biophysical profiling (BPP) may be necessary. However, patients and physicians should be aware that oligohydramnios might not appear until after the foetus has suffered irreparable harm.

• Nursing Mothers

Eprosartan is excreted in animal milk. Eprosartan may pass into human milk, however this is unknown. Considering that many medications are excreted in human milk and so that Eprosartan may produce major negative effects in nursing infants, a choice should be taken regarding whether to stop breastfeeding or to stop the medication, taking into account the significance of drug to the mother.

• Pediatric Use

Patients under the age of 18 year have not been investigated for Eprosartan pharmacokinetics. Hence, safety and effectiveness in pediatric patients have not been established.

• Geriatric Use

29% (681 of 2,334) of the patients taking Eprosartan in clinical investigations were 65 years of age or older, and 5% (124 of 2,334) were 75 years of age or older. The reduction in diastolic and systolic pressure of blood with Eprosartan was however less in patients over 65 compared to younger people, according to pooled data from randomised studies. Eprosartan at 200 mg twice daily (and optionally increased to 300 mg twice daily) lowered diastolic blood pressure on average by 3 mmHg in a study that included only participants over the age of 65. (placebo corrected). Both younger and older patients had negative experiences.

Limited data are available related to overdosage. If an overdose occurs, the proper symptomatic and supportive care should be administered. When rats, mice, and dogs received oral doses of up to 3000 mg of Eprosartan per kilogram of body weight, there was no mortality.

Pharmacodynamic

Angiotensin-converting enzyme [kininase II] enzyme that converts , angiotensin I into angiotensin II, the primary pressor of the renin-angiotensin system. Vasoconstriction, stimulation of aldosterone synthesis and release, heart stimulation, and renal salt reabsorption are only a few of its actions. Eprosartan selectively inhibits angiotensin II binding to the AT1 receptor, which has a number of effects including vasodilation, a decrease in vasopressin secretion, and a decrease in the generation and secretion of aldosterone. A reduction in blood pressure is the final effect.

Pharmacokinetics

• Absorption

Following a single 300 mg oral dose of Eprosartan, its absolute bioavailability is approximately 13%. After taking an oral dose of Eprosartan while fasting, plasma concentrations reach their peak 1 to 2 hours later. Eprosartan use with food produces varied variations (25%) in Cmax and AUC values, that don't appear clinically significant, and slows absorption. Over the dose range of 100 mg to 800 mg, plasma concentrations of Eprosartan rise in a somewhat less than dose-proportional way. Following several 600 mg oral doses, the mean terminal elimination half-life of Eprosartan was 20 hours. With prolonged use, Eprosartan does not considerably accumulate.

• Distribution

Eprosartan has a high, continuous plasma protein binding rate of 98% over the concentration range achieved with therapeutic doses.

• Metabolism and Excretion

Eprosartan is predominantly excreted as an unchanged compound by biliary and renal excretion. The amount of an oral dose that is eliminated in the urine as glucuronide is less than 2%. Following oral and intravenous administration of [14C] Eprosartan to human volunteers, there are no detectable active metabolites. The single drug-related substance detected in the plasma and faeces was Eprosartan. Following the intravenous administration of [14C] Eprosartan, approximately 37% of the material is recovered in the urine and 61% in the faeces.

90% of the [14C] Eprosartan oral dose is recovered in the faeces, and just 7% is recovered in the urine. An acyl glucuronide of Eprosartan made up around 20% of the radioactivity excreted in the urine, with the remaining 80% being unchanged Eprosartan.