Olmesat Id

Uses

Indapamide is used for the treatment of essential hypertension . It is effective in treating hypertension in patients with renal function impairment, although its diuretic effect is reduced. Indapamide is also used for the treatment of salt and fluid retention associated with congestive heart failure.

Olmesartan is used for the treatment of mild to moderate essential hypertension. Olmesartan may be used alone or in combination with thiazide diuretic.

Olmesat Id is also used to associated treatment for these conditions: High Blood Pressure (Hypertension), Recurrent Nephrolithiasis, Sodium and fluid retentionDiabetic Nephropathy, High Blood Pressure (Hypertension), Severe Hypertension, Moderate Hypertension

How Olmesat Id works

Indapamide acts on the nephron, specifically at the proximal segment of the distal convoluted tubule where it inhibits the Na+/Cl- cotransporter, leading to reduced sodium reabsorption. As a result, sodium and water are retained in the lumen of the nephron for urinary excretion. The effects that follow include reduced plasma volume, reduced venous return, lower cardiac output, and ultimately decreased blood pressure.

Interestingly, it is likely that thiazide-like diuretics such as indapamide have additional blood pressure lowering mechanisms that are unrelated to diuresis. This is exemplified by the observation that the antihypertensive effects of thiazides are sustained 4-6 weeks after initiation of therapy, despite recovering plasma and extracellular fluid volumes.

Some studies have suggested that indapamide may decrease responsiveness to pressor agents while others have suggested it can decrease peripheral resistance. Although it is clear that diuresis contributes to the antihypertensive effects of indapamide, further studies are needed to investigate the medication’s ability to decrease peripheral vascular resistance and relax vascular smooth muscle.

Olmesartan belongs to the angiotensin II receptor blocker (ARB) family of drugs, which also includes telmisartan, candesartan, losartan, valsartan, and irbesartan. ARBs selectively bind to angiotensin receptor 1 (AT1) and prevent the protein angiotensin II from binding and exerting its hypertensive effects. As the principal pressor agent of the renin-angiotensin system, Angiotensin II causes vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal reabsorption of sodium. Olmesartan blocks the vasoconstrictor effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in vascular smooth muscle. Its action is, therefore, independent of the pathways for angiotensin II synthesis. Overall, olmesartan's physiologic effects lead to reduced blood pressure, lower aldosterone levels, reduced cardiac activity, and increased excretion of sodium.

Olmesartan also effects on the renin-angiotensin aldosterone system (RAAS) plays an important role in hemostasis and regulation of kidney, vascular, and cardiac functions. Pharmacological blockade of RAAS via AT1 receptor blockade inhibits negative regulatory feedback within RAAS, which is a contributing factor to the pathogenesis and progression of cardiovascular disease, heart failure, and renal disease. In particular, heart failure is associated with chronic activation of RAAS, leading to inappropriate fluid retention, vasoconstriction, and ultimately a further decline in left ventricular function. ARBs have been shown to have a protective effect on the heart by improving cardiac function, reducing afterload, increasing cardiac output and preventing ventricular hypertrophy and remodelling.

Dosage

Olmesat Id dosage

One tablet daily preferably in the morning. In more sever case Indapamide can be combine with other categories of anti-hypertensive agent. The safety and effectiveness in pediatric patients have not been established

Adult:Dosage must be individualized. The usual initial dose is 10 mg once daily. In patients whose blood pressure is not adequately controlled at this dose, the dose may be increased to 20 mg once daily as the optimal dose. For patients requiring further reduction in blood pressure after 2 weeks of therapy, the dose of Olmesartan may be increased to 40 mg. Doses above 40 mg do not appear to have greater effect.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Geriatric Use: Of the total number of hypertensive patients receiving Olmesartan Medoxomil 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.

Side Effects

Side effects of Indapamide include headache, anorexia, gastric irritation,nausea, vomiting, constipation, diarrhoea etc.

Common or very common: Arthritis, chest pain, cough, fatigue, gastro-intestinal disturbances, haematuria, hypertriglyceridaemia, hyperuricaemia, influenza-like symptoms, musculoskeletal pain, peripheral edema, pharyngitis, rhinitis, urinary-tract infection.

Uncommon: Angina, rash, vertigo.

Very rare: Headache, myalgia, pruritus, thrombocytopenia, urticaria.

Toxicity

Indapamide overdose symptoms may include but are not limited to nausea, vomiting, gastrointestinal disorders, electrolyte disturbances and weakness. Other signs of overdose include respiratory depression and severe hypotension. In cases of overdose, supportive care interventions may be necessary to manage symptoms. Emesis and gastric lavage may be recommended to empty the stomach; however, patients should be monitored closely for any electrolyte or fluid imbalances.

The reported LD50 of olmesartan in dogs was reported to be greater of 1500 mg/kg. Overdose is expressed as hypotension, tachycardia, and bradycardia when there is parasympathetic stimulation. In case of overdose, supportive treatment is recommended.

Olmesartan was shown to be safe on carcinogenic and fertility studies. However, in in vitro mutagenic studies showed a potential to induce chromosomal aberrations in cells and it tested positive for thymidine kinase mutations in the mouse lymphoma assay.

Precaution

Monitoring of potassium and uric acid serum levels is recommended, especially in subjects with a predisposition or sensitivity to hypokalemia and in patients with gout. Although no allergic manifestations have been reported during clinical trials, patients with a history of allergy to sulfonamide derivatives should be closely monitored.

Fetal/Neonatal Morbidity and Mortality: Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature of patients who were taking angiotensin converting enzyme inhibitors. When pregnancy is detected, Olmesartan Medoxomil should be discontinued as soon as possible.

Hypotension in Volume- or Salt-Depleted Patients: In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with Olmesartan Medoxomil. Treatment should start under close medical supervision. If hypotension does occur, the patient should be placed in the supine position and, if necessary, given an intravenous infusion of normal saline.

Interaction

Other antihypertensive: Indapamide may add to or potentiate the action of other antihypertensive drugs.

Norepinephrine: Indapamide like thiazides, may decrease arterial responsiveness to norepinephrine.

Lithium: In general, diuretics should not be given concomitantly with lithium because they reduce its renal clearance and add a high risk of lithium toxicity.

No significant drug interactions were reported in studies in which Olmesartan Medoxomil was co-administered with digoxin or warfarin in healthy volunteers. The bioavailability of Olmesartan was not significantly altered by the co-administration of antacids [Al(OH)3/Mg(OH)2]. Olmesartan Medoxomil 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.

Volume of Distribution

Some sources report an apparent volume of distribution of 25 L for indapamide, while others report a value of approximately 60 L.

17 L[L5566]

Elimination Route

The bioavailability of indapamide is virtually complete after an oral dose and is unaffected by food or antacids. Indapamide is highly lipid-soluble due to its indoline moiety - a characteristic that likely explains why indapamide’s renal clearance makes up less than 10% of its total systemic clearance. The Tmax occurs approximately 2.3 hours after oral administration. The Cmax and AUC_0-24 values are 263 ng/mL and 2.95 ug/hr/mL, respectively.

When taken orally, the prodrug olmesartan medoxomil is rapidly absorbed in the gastrointestinal tract and metabolized to olmesartan. The esterification with medoxomil was created with the intention of increasing olmesartan bioavailability from 4.5% to 28.6%.

Oral administration of 10-160 mg of olmesartan has been shown to reach peak plasma concentration of 0.22-2.1 mg/L after 1-3 hours with an AUC of 1.6-19.9mgh/L. The pharmacokinetic profile of olmesartan has been observed to be nearly linear and dose-dependent under the therapeutic range. The steady-state level of olmesartan is achieved after once a day dosing during 3 to 5 days.[L5566]

Half Life

Indapamide is characterized by biphasic elimination. In healthy subjects, indapamide's elimination half-life can range from 13.9 to 18 hours. The long half-life is conducive to once-daily dosing.

The mean plasma olmesartan half-life is reported to be from 10-15 hours after multiple oral administration.

Clearance

Indapamide's renal and hepatic clearance values are reported to be 1.71 mL/min and 20-23.4 mL/min, respectively.

Total plasma clearance is 1.3 L/h and the renal clearance is 0.6 L/h.[L5566]

Elimination Route

An estimated 60-70% of indapamide is eliminated in the urine, while 16-23% is eliminated in the feces.

The main elimination route of olmesartan is in the unchanged form through the feces. From the systemically bioavailable dose, about 10-16% is eliminated in the urine.

Pregnancy & Breastfeeding use

There are no adequate and well-controlled studies in pregnant women and so Indapamide is not recommended. Mothers taking Indapamide should not breast feed.

Pregnancy Categories C (first trimester) and D (second and third trimesters).

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.

Contraindication

This drug must not be taken in the following conditions:

• Hypersensitivity to sulfonamides
• Severe renal failure
• Hepatic encephalopathy or severe hepatic failure
• Hypokalaemia

Olmesartan is contraindicated in patients who are hypersensitive to any component of this product.

Special Warning

Hepatic Impairment: Dose should not exceed 20 mg daily in moderate impairment.

Renal Impairment: Max. 20 mg daily if eGFR 20–60 mL/minute/1.73 m2. Avoid if eGFR less than 20 mL/minute/1.73 m2.

Acute Overdose

Symptoms: These could include: allergies, skin rashes, epigastric pain, nausea, photosensitivity, dizziness, weakness and paraesthesia.Treatment: Treatment is supportive and symptomatic, directed at correcting the electrolyte abnormalities.

Only limited information is available regarding overdosage in humans. The most likely effect of overdosage is hypotension. In the event of overdosage, the patient should be carefully monitored and treatment should be symptomatic and supportive. No information is available regarding the dialysability of olmesartan.

Storage Condition

Store in a cool and dry place. Protect from light and moisture.

Keep out of the reach of children. Keep in the original package in a cool & dry place. Protect from light and moisture.

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