Olmat 20

Olmat 20 which contains the salt Olmesartan 20 mg is an antihypertensive agent belonging to Angiotensin II Receptor Blocker and is approved for use in the following clinical indications:

• Hypertension

Olmat 20 is an angiotensin II receptor blocker that works by inhibiting a compound in the body that leads to blood vessel tightening. As a result, Olmat 20 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 Olmat 20 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 Olmat 20 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

Olmat 20 has been a recommendation to help lower microalbuminuria in patients with diabetes mellitus.

• Cardiovascular Disease

Olmat 20 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 their 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 Olmat 20.

Olmat 20 contains the salt Olmesartan 20 mg and is available in the form of tablets.

• Adult Hypertension: The recommended initial dose of Olmat 20 is 20mg 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 40mg. For patients with impaired renal function and treatment with diuretics with possible depletion of intravascular volume, Olmat 20 is initiated with a low starting dose under close medical supervision.
• Pediatric Hypertension: Dosage is individualized. The usual recommended initial dose of Olmesartan is 10mg once daily for patients who weigh <35 kg or 20mg 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 20mg 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, a dose of 40mg 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 normo-albuminuria.
• Cardiovascular Disease: In patients with chronic cardiovascular disease, short-term (12 weeks) and long-term treatment with Olmesartan 40mg was well tolerated, lowering BP more effectively.

• Fetal Toxicity: Olmat 20 can cause fetal damage when administered to a pregnant female. There is a disturbance in 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 Olmat 20 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 Olmat 20. 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 Olmat 20.
• 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 Olmat 20. 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 Olmat 20.
• Sprue-Like Enteropathy: Severe, chronic diarrhea with substantial weight loss has been reported in patients taking Olmat 20 months to years after drug initiation. Intestinal biopsies of patients often demonstrated villous atrophy. If a patient develops these symptoms during treatment with Olmat 20, exclude other etiologies. Consider alternative antihypertensive therapy in cases where no other etiology is identified.
• Hyperkalemia: Serum potassium should be monitored in patients receiving Olmat 20. 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.

Olmat 20 contains the salt Olmesartan 20 mg and can cause the following reactions:

• 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 Olmat 20 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 Olmat 20 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 Olmat 20 medoxomil and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including Olmat 20 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 the combined use of RAS inhibitors. Closely monitor blood pressure, renal function, and electrolytes in patients on Olmat 20 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 Olmat 20. 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 Olmat 20. Administration of Olmat 20 at least 4 hours prior to colesevelam hydrochloride decreased the drug interaction effect. Consider administering Olmat 20 at least 4 hours before the colesevelam hydrochloride dose.

The use of the molecule Olmat 20 contains the salt Olmesartan 20 mg 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 Olmat 20 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 Olmat 20, 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 Olmat 20 for hypotension, oliguria, and hyperkalemia.

• Nursing Mothers

It is not known whether Olmat 20 is excreted in human milk, but Olmat 20 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 Olmat 20: 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 Olmat 20 were evaluated in one randomized, double-blind clinical study in pediatric patients 1 to 16 years of age. The pharmacokinetics of Olmat 20 were evaluated in pediatric patients 1 to 16 years. Olmat 20 was generally well tolerated in pediatric patients, and the adverse experience profile was similar to that described for adults. Olmat 20 has not been shown to be effective for hypertension in children <6 years of age.

Children <1 year of age must not receive Olmat 20 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 Olmat 20 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 Olmat 20 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).

Pharmacodynamics:

Olmat 20 doses of 2.5mg to 40mg restrict the pressure effects of angiotensin I infusion. The prolongation of the inhibitory effect was related to dose, with doses of Olmat 20 >40mg, which inhibit at 24 hours. The Plasma concentrations of angiotensin I and angiotensin II rise after single and repeated administration of Olmat 20 to hypertensive patients. Recurrent administration of up to 80mg of Olmat 20 has minimal influence on aldosterone levels and no effect on serum potassium.

Pharmacokinetics

Absorption:

Olmat 20 undergoes rapid and complete bioactivation by hydrolysis with the ester to Olmat 20 in the course of absorption from the gastrointestinal tract. The bioavailability of Olmat 20 is approximately 26%. After administration, the peak plasma concentration of Olmat 20 is gained after 1 to 2 hours. Food does not impact the bioavailability of Olmat 20. It can be administered with or without food. The bioavailability of Olmat 20 is 26%, and the peak plasma concentration of Olmat 20 is reached after 1-2 hours of oral administration.

Distribution:

The volume of distribution of Olmat 20 is about 17 L. Olmat 20 is bound to plasma proteins and does not enter red blood cells. The protein binding is constant level at plasma Olmat 20 concentrations well above the range achieved with recommended doses.

Metabolism And Excretion

After the rapid and complete conversion of Olmat 20 in the course of absorption, there is no further metabolism of Olmat 20. The total plasma clearance of Olmat 20 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. Olmat 20 shows linear pharmacokinetics after single oral doses of up to 320mg and multiple oral doses of up to 80mg. Steady-state levels of Olmat 20 are reached within 3 to 5 days, and no accumulation in plasma occurs with once-daily dosing.