Olmesar Av

Uses

Atorvastatin is an HMG-CoA reductase inhibitor used to lower lipid levels and reduce the risk of cardiovascular disease including myocardial infarction and stroke.

Atorvastatin is indicated for the treatment of several types of dyslipidemias, including primary hyperlipidemia and mixed dyslipidemia in adults, hypertriglyceridemia, primary dysbetalipoproteinemia, homozygous familial hypercholesterolemia, and heterozygous familial hypercholesterolemia in adolescent patients with failed dietary modifications.

Dyslipidemia describes an elevation of plasma cholesterol, triglycerides or both as well as to the presence of low levels of high-density lipoprotein. This condition represents an increased risk for the development of atherosclerosis.

Atorvastatin is indicated, in combination with dietary modifications, to prevent cardiovascular events in patients with cardiac risk factors and/or abnormal lipid profiles.

Atorvastatin can be used as a preventive agent for myocardial infarction, stroke, revascularization, and angina, in patients without coronary heart disease but with multiple risk factors and in patients with type 2 diabetes without coronary heart disease but multiple risk factors.

Atorvastatin may be used as a preventive agent for non-fatal myocardial infarction, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure and angina in patients with coronary heart disease.

Prescribing of statin medications is considered standard practice following any cardiovascular events and for people with a moderate to high risk of development of CVD. Statin-indicated conditions include diabetes mellitus, clinical atherosclerosis (including myocardial infarction, acute coronary syndromes, stable angina, documented coronary artery disease, stroke, trans ischemic attack (TIA), documented carotid disease, peripheral artery disease, and claudication), abdominal aortic aneurysm, chronic kidney disease, and severely elevated LDL-C levels.

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

Olmesar Av is also used to associated treatment for these conditions: Anginal Pain, Cardiovascular Disease (CVD), Coronary Artery Disease (CAD), Coronary artery thrombosis, Dysbetalipoproteinemia, Fredrickson Type III lipidemia, Heterozygous Familial Hypercholesterolemia, High Blood Pressure (Hypertension), High Cholesterol, Homozygous Familial Hypercholesterolemia, Hospitalizations, Hypertriglyceridemias, Mixed Dyslipidemias, Mixed Hyperlipidemia, Myocardial Infarction, Non-familial hypercholesterolemia, Postoperative Thromboembolism, Primary Hypercholesterolemia, Stroke, Transient Ischemic Attack, Elevation of serum triglyceride levels, Heterozygous familial hyperlipidemia, Non-familial hyperlipidemia, Non-fatal myocardial infarction, Primary Hyperlipidemia, Revascularization procedures, Revascularization process, Thrombotic events, Cardiovascular Primary Prevention, Secondary prevention cardiovascular eventDiabetic Nephropathy, High Blood Pressure (Hypertension), Severe Hypertension, Moderate Hypertension

How Olmesar Av works

Atorvastatin is a statin medication and a competitive inhibitor of the enzyme HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase, which catalyzes the conversion of HMG-CoA to mevalonate, an early rate-limiting step in cholesterol biosynthesis. Atorvastatin acts primarily in the liver, where decreased hepatic cholesterol concentrations stimulate the upregulation of hepatic low-density lipoprotein (LDL) receptors, which increases hepatic uptake of LDL. Atorvastatin also reduces Very-Low-Density Lipoprotein-Cholesterol (VLDL-C), serum triglycerides (TG) and Intermediate Density Lipoproteins (IDL), as well as the number of apolipoprotein B (apo B) containing particles, but increases High-Density Lipoprotein Cholesterol (HDL-C).

In vitro and in vivo animal studies also demonstrate that atorvastatin exerts vasculoprotective effects independent of its lipid-lowering properties, also known as the pleiotropic effects of statins. These effects include improvement in endothelial function, enhanced stability of atherosclerotic plaques, reduced oxidative stress and inflammation, and inhibition of the thrombogenic response. Statins were also found to bind allosterically to β2 integrin function-associated antigen-1 (LFA-1), which plays an essential role in leukocyte trafficking and T cell activation.

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

Olmesar Av dosage

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

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

The reported LD50 of oral atorvastatin in mice is higher than 5000 mg/kg. In cases of overdose with atorvastatin, there is reported symptoms of complicated breathing, jaundice, liver damage, dark urine, muscle pain, and seizures. In case of overdose, symptomatic treatment is recommended and due to the high plasma protein binding, hemodialysis is not expected to generate significant improvement.

In carcinogenic studies with high doses of atorvastatin, evidence of rhabdomyosarcoma, fibrosarcoma, liver adenoma, and liver carcinoma were observed.

In fertility studies with high doses of atorvastatin, there were events of aplasia, aspermia, low testis and epididymal weight, decreased sperm motility, decreased spermatid head concentration and increased abnormal sperm.

Atorvastatin was shown to not be mutagenic in diverse mutagenic assays.

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

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

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

The reported volume of distribution of atorvastatin is of 380 L.

17 L[L5566]

Elimination Route

Atorvastatin presents a dose-dependent and non-linear pharmacokinetic profile. It is very rapidly absorbed after oral administration. After the administration of a dose of 40 mg, its peak plasma concentration of 28 ng/ml is reached 1-2 hours after initial administration with an AUC of about 200 ng∙h/ml. Atorvastatin undergoes extensive first-pass metabolism in the wall of the gut and the liver, resulting in an absolute oral bioavailability of 14%. Plasma atorvastatin concentrations are lower (approximately 30% for Cmax and AUC) following evening drug administration compared with morning. However, LDL-C reduction is the same regardless of the time of day of drug administration.

Administration of atorvastatin with food results in prolonged Tmax and a reduction in Cmax and AUC.

Breast Cancer Resistance Protein (BCRP) is a membrane-bound protein that plays an important role in the absorption of atorvastatin. Evidence from pharmacogenetic studies of c.421C>A single nucleotide polymorphisms (SNPs) in the gene for BCRP has demonstrated that individuals with the 421AA genotype have reduced functional activity and 1.72-fold higher AUC for atorvastatin compared to study individuals with the control 421CC genotype. This has important implications for the variation in response to the drug in terms of efficacy and toxicity, particularly as the BCRP c.421C>A polymorphism occurs more frequently in Asian populations than in Caucasians. Other statin drugs impacted by this polymorphism include fluvastatin, simvastatin, and rosuvastatin.

Genetic differences in the OATP1B1 (organic-anion-transporting polypeptide 1B1) hepatic transporter encoded by the SCLCO1B1 gene (Solute Carrier Organic Anion Transporter family member 1B1) have been shown to impact atorvastatin pharmacokinetics. Evidence from pharmacogenetic studies of the c.521T>C single nucleotide polymorphism (SNP) in the gene encoding OATP1B1 (SLCO1B1) demonstrated that atorvastatin AUC was increased 2.45-fold for individuals homozygous for 521CC compared to homozygous 521TT individuals.[A181493] Other statin drugs impacted by this polymorphism include simvastatin, pitavastatin, rosuvastatin, and pravastatin.

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

The half-life of atorvastatin is 14 hours while the half-life of its metabolites can reach up to 30 hours.

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

Clearance

The registered total plasma clearance of atorvastatin is of 625 ml/min.

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

Elimination Route

Atorvastatin and its metabolites are mainly eliminated in the bile without enterohepatic recirculation. The renal elimination of atorvastatin is very minimal and represents less than 1% of the eliminated dose.

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

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

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

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

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

Innovators Monograph

You find simplified version here Olmesar Av