Olmetec

Olmetec

olmesartan

Manufacturer:

Pfizer

Distributor:

Zuellig
Full Prescribing Info
Contents
Olmesartan medoxomil.
Description
Olmetec 10 mg Tablet: Each tablet contains 10 mg of olmesartan medoxomil.
Olmetec 20 mg Tablet: Each tablet contains 20 mg of olmesartan medoxomil.
Olmetec 40 mg Tablet: Each tablet contains 40 mg of olmesartan medoxomil.
OLMETEC (olmesartan medoxomil), a prodrug, which is hydrolysed to the active metabolite olmesartan during absorption from the gastrointestinal tract. Olmesartan is a selective AT1 subtype angiotensin II receptor antagonist.
Olmesartan medoxomil is described chemically as (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylate. Alternatively, it can be described as 2,3-dihydroxy-2-butenyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[p-(o-1H-tetrazol-5-ylphenyl)benzyl]imidazole-5-carboxylate, cyclic 2,3-carbonate.
Its empirical formula is C29H30N6O6.
Olmesartan medoxomil is a white to light yellowish-white powder or crystalline powder with a molecular weight of 558.59. It is practically insoluble in water and sparingly soluble in methanol.
Action
Pharmacologic Category: Antihypertensive (Angiotensin II Receptor Blocker).
Pharmacology: Pharmacodynamics: Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of the 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 pathway of angiotensin II synthesis.
Oral doses of olmesartan medoxomil 2.5 to 40 mg inhibited the pressor response to exogenous angiotensin I infusion.
Plasma concentrations of angiotensin I, angiotensin II and plasma renin activity increased after single or repeated administration of olmesartan medoxomil to healthy subjects or hypertensive patients. Olmesartan medoxomil administration had little effect on plasma levels of aldosterone.
In clinical trials in hypertensive patients, olmesartan medoxomil treatment resulted in a dose-dependent reduction in arterial blood pressure. The blood pressure-lowering effect of olmesartan medoxomil in a once-daily regimen was maintained throughout the 24-hour dose interval. The efficacy of olmesartan medoxomil, with or without added hydrochlorothiazide as needed, was maintained for up to at least 1 year. There was no evidence of rebound hypertension following interruption of therapy at the 1 year time point.
Olmesartan medoxomil was effective in lowering blood pressure regardless of gender, age or race, although the effect appeared to be somewhat less in black patients (usually a low-renin population).
Clinical Trials: The Randomized Olmesartan And Diabetes Microalbuminuria Prevention (ROADMAP) clinical study included 4447 patients with type 2 diabetes, normoalbuminuria and at least one additional cardiovascular risk factor. Patients were randomized to olmesartan 40 mg daily or placebo. The trial met its primary endpoint, delayed onset of microalbuminuria. For the secondary endpoints, which the study was not designed to formally assess, cardiovascular events occurred in 96 patients (4.3%) with olmesartan and in 94 patients (4.2%) with placebo. The incidence of cardiovascular mortality was higher with olmesartan compared to placebo treatment [15 patients (0.67%) vs. 3 patients (0.14%) (HR=4.94, 95% CI=1.43-17.06)], but the risk of non-fatal myocardial infarction was lower with olmesartan (HR 0.64, 95% CI 0.35, 1.18).
Pharmacokinetics: Absorption and Distribution: Following oral administration, olmesartan medoxomil is rapidly metabolized to its pharmacologically active metabolite, olmesartan. The mean absolute bioavailability of olmesartan from a tablet formulation was found to be about 26%.
The mean peak plasma concentration of olmesartan is reached within about 2 hours after oral dosing with olmesartan medoxomil, and olmesartan plasma concentrations increase approximately linearly with increasing single or repeated oral doses over the therapeutic range.
Food does not affect the bioavailability of olmesartan.
No clinically relevant gender-related differences in the pharmacokinetics of olmesartan have been observed.
Olmesartan is highly bound to plasma protein (99%). The mean volume of distribution after intravenous dosing is in the range of 16-29 L.
In rats, olmesartan crossed the blood-brain barrier poorly, if at all. Olmesartan crossed the placental barrier in rats and was distributed to the fetus. Olmesartan was distributed to milk at low levels in rats.
Metabolism and Elimination: Following the rapid and complete conversion of olmesartan medoxomil to olmesartan during absorption, there is virtually no further metabolism of olmesartan. Approximately 30% to 50% of the systematically absorbed drug is excreted in the urine whilst the remainder is excreted in feces (via the bile).
Depending on ethnic origin, the terminal elimination half-life of olmesartan varied between 6-15 hours. Steady state was reached after the first few doses and no further accumulation was evident with repeated dosing. Renal clearance was approximately 0.5-0.7 L/h.
Pharmacokinetics in Special Populations: Elderly: In Caucasian patients, the AUC at steady state was increased by about 33% in elderly patients. These increases in bioavailability corresponded to reductions in renal clearance of about 30% in elderly.
Renal Impairment: In patients with renal insufficiency, serum concentrations of olmesartan were elevated 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).
The pharmacokinetics of olmesartan in patients undergoing hemodialysis has not been studied.
Hepatic Impairment: Mean olmesartan AUC after single oral administration to patients with moderate hepatic impairment was increased by about 48% compared with healthy controls (total group), or by about 60% when compared with, matched controls only.
Interactions: No significant pharmacokinetic interactions were observed in studies in which olmesartan medoxomil was co-administered with digoxin or warfarin in healthy volunteers. The bioavailability of olmesartan was not significantly affected by antacid (aluminum, magnesium hydroxide). 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 these enzymes are not expected.
Drug Interaction with Bile Acid Sequestering Agent, Colesevelam: Concomitant administration of 40 mg olmesartan medoxomil and 3750 mg colesevelam hydrochloride in healthy subjects resulted in 28% reduction in Cmax and 39% reduction in AUC of olmesartan. Lesser effects, 4% and 15% reduction in Cmax and AUC respectively, were observed when olmesartan medoxomil was administered 4 hours prior to colesevelam hydrochloride (see Interactions).
Toxicology: Preclinical Safety Data: Preclinical carcinogenicity studies revealed no clinically relevant risk for humans.
In reproductive studies in rats, olmesartan medoxomil did not affect fertility. In common with other angiotensin II antagonists, survival of offspring was reduced following exposure to olmesartan medoxomil and pelvic dilatation of the kidney was seen after exposure of the dams in late pregnancy and lactation. In common with other antihypertensive agents, olmesartan medoxomil was shown to be more toxic to pregnant rabbits than to pregnant rats; however, there was no indication of a fetotoxic effect.
Indications/Uses
Olmesartan medoxomil is indicated for the treatment of hypertension.
Dosage/Direction for Use
Usual Adult Dose: The usual recommended dose of olmesartan medoxomil is in the range 10-40 mg once daily, adjusted according to patient need. If required, further antihypertensive therapy may be used concomitantly with olmesartan medoxomil to achieve blood pressure control.
Elderly: No initial dosage adjustment is recommended for elderly patients.
Renal Impairment: Dosage of olmesartan medoxomil should be individualized in patients with renal impairment.
There is no experience in the use of olmesartan medoxomil in patients requiring dialysis. See Precautions for further information on renal impairment.
Hepatic Impairment: No initial dosage adjustment is recommended in patients with mild to moderate hepatic impairment.
Children: The safety and efficacy of olmesartan medoxomil have not been established in children.
Overdosage
Only limited data relevant to overdosage with olmesartan medoxomil in humans are available. The most likely effect of overdosage is hypotension. In the event of overdosage, treatment should be supportive.
No information is available regarding the dialysability of olmesartan.
Contraindications
Olmesartan medoxomil is contraindicated in patients who are hypersensitive to any component of the tablet, such as microcrystalline cellulose, low substituted hydroxypropylcellulose, lactose, hydroxypropylcellulose and magnesium stearate, talc, titanium dioxide and hypromellose.
Patients who become pregnant should discontinue the use of olmesartan medoxomil as soon as possible unless no alternative to a drug acting on the renin-angiotensin system can be found. See Use in Pregnancy & Lactation.
Do not co-administer aliskiren with olmesartan medoxomil in patients with diabetes (see Interactions).
Special Precautions
Volume- or Salt-Depleted Patients and Patients with Activated Renin-Angiotensin System: 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 following the initiation of treatment with olmesartan medoxomil.
Impaired Renal Function: In patients whose renal function may depend predominantly on the activity of the renin-angiotensin system, treatment with drugs that affect this system has been associated with azotemia, oliguria or, rarely, acute renal failure.
There is an increased risk of renal insufficiency when patients with bilateral renal artery stenosis (or stenosis of the artery to a single functioning kidney) are treated with medicinal products that affect the renin-angiotensin system.
Sprue-Like Enteropathy: Severe, chronic diarrhea with substantial weight loss has been reported in patients taking olmesartan medoxomil months to years after drug initiation. Intestinal biopsies of patients often demonstrated villous atrophy. If a patient develops these symptoms during treatment with olmesartan medoxomil, exclude other etiologies. Consider discontinuation of olmesartan medoxomil in cases where no other etiology is identified.
Use In Pregnancy & Lactation
Use in Pregnancy: Use of drugs which act directly on the renin-angiotensin system during the second and third trimesters of pregnancy has been associated with fetal injury and even death. Patients who become pregnant whilst using olmesartan medoxomil should discontinue treatment as soon as possible.
Use in Lactation: 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.
Adverse Reactions
Clinical Trial Experience: Dizziness has been reported commonly (≥1% <10% incidence) in clinical trials with olmesartan medoxomil.
Post-Launch Experience: In post-launch experience, adverse drug reactions which have been reported very rarely (<0.01% incidence) are: Peripheral edema, headache, cough, abdominal pain, nausea, vomiting, diarrhea, sprue-like enteropathy, anaphylactic reaction, rash, pruritus, angioedema, acute renal failure, increased hepatic enzymes, increased blood creatinine, hyperkalemia, myalgia and asthenic conditions, such as asthenia, fatigue, lethargy, malaise.
Drug Interactions
Use with 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.
Dual Blockade of the Renin-Angiotensin System (RAS): Dual blockade of the RAS with angiotensin receptor antagonists, ACE inhibitors or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy. Monitor blood pressure, renal function and electrolytes in patients on olmesartan and other agents that affect the RAS.
Use with Aliskiren: Do not co-administer aliskiren with olmesartan medoxomil in patients with diabetes (see Contraindications) because dual use is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): NSAIDs and ARBs may act synergistically by decreasing glomerular filtration. The concomitant use of NSAIDs and ARBs may increase the risk of worsening renal function.
Additionally, the antihypertensive effect of ARBs, including olmesartan, may be attenuated by NSAIDs, including selective COX2 inhibitors.
Use with 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 (see Pharmacology under Actions).
Storage
Store at temperatures not exceeding 30°C.
ATC Classification
C09CA08 - olmesartan medoxomil ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
Presentation/Packing
FC tab 10 mg (white, circular, with C13 embossed on one side) x 30's. 20 mg (white, circular, with C14 embossed on one side) x 30's. 40 mg (white, oval, with C15 embossed on one side) x 30's.
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