Olmesartan

Olmesartan is an antihypertensive agent belonging to the Angiotensin II receptor blocker class. Olmesartan is approved for the treatment of hypertension, alone or with other antihypertensive agents, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and heart attacks.

The absolute bioavailability of Olmesartan is approximately 26%. After oral administration, the peak plasma concentration (Cmax) of Olmesartan is reached after 1 to 2 hours. The volume of distribution of Olmesartan is approximately 17 L. Olmesartan is highly bound to plasma proteins (99%) and does not penetrate red blood cells. Following the rapid and complete conversion of Olmesartan medoxomil to Olmesartan during absorption, there is virtually no further metabolism of Olmesartan. Total plasma clearance of Olmesartan is 1.3 L/h, with a renal clearance of 0.6 L/h. Approximately 35% to 50% of the absorbed dose is recovered in urine while the remainder is eliminated in feces via the bile.

The common side effects associated with Olmesartan include cough, nausea, headache, diarrhea, upset stomach, etc.

Olmesartan is available in the form of tablets.

Olmesartan is available in India, US, Canada, Japan, Europe, South America, Thailand, Philippines.

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

Olmesartan is both reversible and selective, binding to the AT-I receptor at an affinity of over 12000 times its affinity for AT-II subtypes. This molecule inhibits these receptors at the adrenal gland and vascular smooth muscle sites, specifically the arterioles. Physiologically, angiotensin II binds to the AT-I/AT-II receptors, resulting in aldosterone release from the adrenal gland causing arteriolar vasoconstriction. The competitive binding of Olmesartan antagonizes these effects to help lower blood pressure by decreasing arteriolar resistance through vasodilation, which lowers blood pressure. Olmesartan competitively blocks the binding of AT-II to its receptor, thus inhibiting the release of aldosterone from the zona glomerulosa of the adrenal cortex. The reduction in serum aldosterone, in turn, results in reduced expression of ENaC channels within the distal collecting tubule of the nephron leading to decreased sodium reabsorption

The time taken for Olmesartan to show its effect is not clinically established.

Olmesartan effect may remain in your body for approximately 24 hours.

The Tmax was found within 1-2 hours following the administration of Olmesartan, and the Cmax was about 220-2100 ng/mL.

Olmesartan is available in the form of Tablets.

Olmesartan tablet is taken as directed by the physician, and the regular tablet is often taken once a day swallowed with plenty of water, with or without Food.

Olmesartan is approved for the treatment of Hypertension or high blood pressure, which helps in lowering high blood pressure and reduces the risk of strokes and heart attacks.

Olmesartan is also found to bring about regression of proteinuria in diabetic and nondiabetic, hypertensive patients with kidney diseases and those with renal failure.

Olmesartan is an antihypertensive agent belonging to Angiotensin II Receptor Blocker which blocks vasoconstrictor and aldosterone secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to AT1 receptor. Hence the relaxation of blood vessels, so blood flows more efficiently to treat high blood pressure or Hypertension.

Olmesartan is approved for use in the following clinical indications:

• Hypertension

Olmesartan is an angiotensin II receptor blocker that works by inhibiting a compound in the body that leads to blood vessel tightening. As a result, Olmesartan relaxes the blood vessels lowering the blood pressure and increasing the blood supply and oxygen to the heart.

Adult Hypertension: The recommended initial dose of Olmesartan is 20 mg once daily when used as monotherapy in patients who are not volume contracted. For patients requiring a further decrease in blood pressure after two weeks of therapy, the dose of Olmesartan is increased to 40 mg. For patients with impaired renal function and treatment with diuretics with possible depletion of intravascular volume, Olmesartan is initiated with a low starting dose under close medical supervision.

Pediatric Hypertension: Dosage is individualized. The usual recommended initial dose of Olmesartan is 10 mg once daily for patients who weigh <35 kg or 20 mg once every day for patients who weigh ≥35 kg for pediatric patients. For patients requiring a further decrease in blood pressure after two weeks of therapy, the dose of Olmesartan is increased to a maximum of 20 mg once daily for patients who weigh <35 kg. Use of Olmesartan in children under one year of age is not recommended.

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

• Delay Progression of proteinuria in Diabetes Mellitus

Olmesartan have been a recommendation to help lower microalbuminuria in patients with diabetes mellitus.

• Cardiovascular Disease

Olmesartan can also lower cardiovascular events and mortality in ischemic heart disease in clinical practice. However, ARB medications are inferior when compared to the use of ACE inhibitors. While ACE inhibitors are generally considered first-line agents in the treatment of hypertension, they can cause a bradykinin-induced cough, deterring patients from its use. In patients who cannot tolerate ACE-inhibitor medications due to side effects, the recommendation is to change from ACE-I to ARB medication, such as Olmesartan.

Olmesartan is available in the form of tablets.

• Adult Hypertension: The recommended initial dose of Olmesartan is 20 mg once daily when used as monotherapy in patients who are not volume contracted. For patients requiring a further decrease in blood pressure after two weeks of therapy, the dose of Olmesartan is increased to 40 mg. For patients with impaired renal function and treatment with diuretics with possible depletion of intravascular volume, Olmesartan is initiated with a low starting dose under close medical supervision.
• Pediatric Hypertension: Dosage is individualized. The usual recommended initial dose of Olmesartan is 10 mg once daily for patients who weigh <35 kg or 20 mg once every day for patients who weigh ≥35 kg for pediatric patients. For patients requiring a further decrease in blood pressure after two weeks of therapy, the dose of Olmesartan is increased to a maximum of 20 mg once daily for patients who weigh <35 kg. Use of Olmesartan in children under one year of age is not recommended.
• Delay Progression of proteinuria in Diabetes Mellitus: In patients with diabetes mellitus, at a dose of 40 mg daily prevents or delays the time to the first occurrence of microalbuminuria in patients who have type 2 diabetes, as well as at least one other cardiovascular risk factor, and normoalbuminuria.
• Cardiovascular Disease:

In patients with chronic cardiovascular disease, short-term (12 weeks) and long-term treatment with Olmesartan 40mg was well tolerated, lowered BP more effectively.

Olmesartan is available in dosage strengths of 5mg, 20mg, and 40mg.

Olmesartan is available in the dosage form of Tablets.

• Hypertension:

Salt substitutes containing potassium are avoided, and low salt or low sodium diet is maintained systematically.

The dietary restriction should be individualized as per patient requirements.

Olmesartan may be contraindicated in the following:

• Do not co-administer aliskiren with Olmesartan in patients with diabetes.
• Hypersensitivity
• Concurrent use of ACE inhibitors
• Pregnancy (especially second/third trimester)
• Severe renal impairment
• History of hypotension
• Hyperkalemia

• Fetal Toxicity: Olmesartan can cause fetal damage when administered to a pregnant female. There is a disturbance in the fetal renal function and an increase in fetal and neonatal morbidity and death with the use of drugs that act on the renin-angiotensin system (RAS) during the second and third trimesters of pregnancy.
• Morbidity In Infants: The use of Olmesartan in children less than one year of age is not recommended. Drugs directly acting on the renin-angiotensin-aldosterone system (RAAS) 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, symptomatic hypotension may be anticipated after initiation of treatment with Olmesartan. Patients that are treated with high doses of diuretics have an activated renin-angiotensin-aldosterone system, such as in volume or salt-depleted patients; symptomatic hypotension may be anticipated after initiation of treatment with Olmesartan.
• Impaired Renal Function: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals treated with Olmesartan. In patients whose renal function may depend upon the activity of the renin-angiotensin aldosterone system (e.g., patients with severe congestive heart failure), treatment with angiotensin converting enzyme (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 be anticipated in patients treated with Olmesartan.
• 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 treatment with Olmesartan, exclude other etiologies. Consider alternative antihypertensive therapy in cases where no other etiology is identified.
• Hyperkalemia: Serum potassium should be monitored in patients receiving Olmesartan. 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 potassium-sparing diuretics, potassium supplements and/or potassium-containing salt substitutes.

Intake of alcohol with Olmesartan can cause drowsiness, dizziness, lightheadedness, or fainting; therefore, is better to avoid alcohol while taking Olmesartan.

It is not known whether Olmesartan is excreted in human milk, but Olmesartan is secreted at low concentration in the milk of lactating rats. 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.

Olmesartan is an angiotensin II receptor blocker that should not be initiated during pregnancy as it can lead to fetal harm when administered to pregnant women. Olmesartan can reduce fetal renal function and result in oligohydramnios related to skeletal deformities. Patients planning pregnancy should be considered alternative antihypertensive treatments with an established safety profile for use in pregnancy.

Olmesartan is used in caution with food rich in potassium, such as bananas, nuts, and sweet potatoes, as it can lead to hyperkalemia.

• Common: Blood in the urine, body pain, chills, cough or cough producing mucus, difficulty with breathing, ear congestion, fever, headache, loss of voice, runny or stuffy nose.
• Infrequent adverse effects: Confusion, dark-colored urine, diarrhea (severe) with weight loss, dizziness, hives or itching
• Rare adverse effects: Bladder pain, bloating or swelling of the face, arms, hands, lower legs, chest pain, cloudy urine, burning or painful urination, fast or irregular heartbeat or pulse, frequent urge to urinate, joint pain, stiffness, or swelling.

• Agents Increasing Serum Potassium

Concomitant use of Olmesartan with other agents that block the renin-angiotensin system, potassium-sparing diuretics (e.g., spironolactone, triamterene, amiloride), potassium supplements, salt substitutes containing potassium or other drugs that may increase potassium levels (e.g., heparin) may lead to increases in serum potassium. If co-medication is considered necessary, monitoring of serum potassium is advisable.

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

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.

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

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 Olmesartan and other agents that affect the RAS.

• Lithium

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

• 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

The common side of Olmesartan includes the following:

Major side effects

• Back pain
• Headache
• Chills
• Nasal congestion
• Unusual tiredness and weakness
• Blood in urine
• Diarrhea
• Dry mouth
• Dizziness
• Nausea
• Upset stomach

Minor side effects

• Joint pain
• Swelling of feet and lower legs
• Bladder pain
• Skin rash

The use of the molecule Olmesartan should be prudent in the following group of special populations:

Pregnancy

• Pregnancy Category D

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformities. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Olmesartan as soon as possible. These adverse outcomes are usually associated with use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Olmesartan, unless it is considered lifesaving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Olmesartan for hypotension, oliguria, and hyperkalemia.

• Nursing Mothers

It is not known whether olmesartan is excreted in human milk, but olmesartan is secreted at low concentration in the milk of lactating rats. 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 Use

Neonates with a history of in utero exposure to Olmesartan: If oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function. The antihypertensive effects of Olmesartan were evaluated in one randomized, double-blind clinical study in pediatric patients 1 to 16 years of age. The pharmacokinetics of Olmesartan were evaluated in pediatric patients 1 to 16 years. Olmesartan was generally well tolerated in pediatric patients, and the adverse experience profile was similar to that described for adults. Olmesartan has not been shown to be effective for hypertension in children <6 years of age.

Children <1 year of age must not receive Olmesartan for hypertension. The renin-angiotensin aldosterone system (RAAS) plays a critical role in kidney development. RAAS blockade has been shown to lead to abnormal kidney development in very young mice. Administering drugs that act directly on the renin angiotensin aldosterone system (RAAS) can alter normal renal development.

• Geriatric Use

Of the total number of hypertensive patients receiving Olmesartan in clinical studies, more than 20% were 65 years of age and over, while more than 5% were 75 years of age and older. 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.

• Hepatic Impairment

Increases in AUC0-¥ and Cmax were observed in patients with moderate hepatic impairment compared to those in matched controls, with an increase in AUC of about 60%. No initial dosage adjustment is recommended for patients with moderate to marked hepatic dysfunction.

• Renal Impairment

Patients with renal insufficiency have elevated serum concentrations of Olmesartan compared to subjects with normal renal function. After repeated dosing, the AUC was approximately tripled in patients with severe renal impairment (creatinine clearance <20 mL/min). No initial dosage adjustment is recommended for patients with moderate to marked renal impairment (creatinine clearance <40 mL/min).

Limited data are available related to overdosage in humans. The most likely manifestations of overdosage would be hypotension and tachycardia; bradycardia could be encountered if parasympathetic (vagal) stimulation occurs. If symptomatic hypotension occurs, initiate supportive treatment. The dialyzability of Olmesartan is unknown.

Pharmacodynamics:

Olmesartan doses of 2.5 mg to 40 mg restrict the pressor effects of angiotensin I infusion. The prolongation of the inhibitory effect was related to dose, with doses of Olmesartan >40 mg, which inhibit at 24 hours. The Plasma concentrations of angiotensin I and angiotensin II rise after single and repeated administration of Olmesartan to hypertensive patients. Recurrent administration of up to 80 mg Olmesartan has minimal influence on aldosterone levels and no effect on serum potassium.

Pharmacokinetics

Absorption:

Olmesartan medoxomil undergoes rapid and complete bioactivation by hydrolysis with the ester to olmesartan in the course of absorption from the gastrointestinal tract. The bioavailability of Olmesartan is approximately 26%. After administration, the peak plasma concentration of olmesartan is gained after 1 to 2 hours. Food does not impact the bioavailability of olmesartan. It can be administered with or without food. The bioavailability of Olmesartan is 26%, and the peak plasma concentration of olmesartan is reached after 1-2 hours of oral administration.

Distribution:

The volume of distribution of olmesartan is about 17 L. Olmesartan is bound to plasma proteins and does not enter red blood cells. The protein binding is constant level at plasma olmesartan concentrations well above the range achieved with recommended doses.

Metabolism And Excretion

After the rapid and complete conversion of olmesartan medoxomil to olmesartan in the course of absorption, there is no further metabolism of olmesartan. The total plasma clearance of olmesartan is 1.3 L/h, with a renal clearance of 0.6 L/h. About 50% of the absorbed dose is recovered in urine, while the leftover is eliminated in feces via the bile. Olmesartan shows linear pharmacokinetics after single oral doses of up to 320 mg and multiple oral doses of up to 80 mg. Steady-state levels of olmesartan are reached within 3 to 5 days, and no accumulation in plasma occurs with once-daily dosing.