Instructions Cardosal 20 mg film-coated tablets 20 mg blister No. 28
Composition
active ingredient: olmesartan medoxomil;
1 film-coated tablet contains 20 mg of olmesartan medoxomil;
Excipients: microcrystalline cellulose, low-substituted hydroxypropylcellulose, lactose monohydrate, hydroxypropylcellulose, magnesium stearate, titanium dioxide (E 171), talc, hypromellose.
Dosage form
Film-coated tablets.
Main physicochemical properties: round tablets, white in color, film-coated, with a characteristic odor, approximately 8.5 mm in diameter, embossed with "C14" on one side.
Pharmacotherapeutic group
Angiotensin II receptor blockers. ATC code C09C A08.
Pharmacological properties
Pharmacodynamics.
Pharmacodynamic properties.
Olmesartan medoxomil is a potent, orally active, selective angiotensin II receptor (type AT1) antagonist. It is expected to block all actions of angiotensin II mediated by the AT1 receptor, regardless of the source and route of synthesis of angiotensin II. Selective antagonism of the AT1 angiotensin II receptor results in increases in plasma renin levels and concentrations of angiotensin I and II, and some reduction in plasma aldosterone concentrations.
Angiotensin II is the main vasoactive hormone of the renin-angiotensin-aldosterone system and plays an important role in the pathophysiology of arterial hypertension through type 1 (AT1) receptors.
Clinical efficacy and safety.
In hypertension, olmesartan medoxomil produces a dose-dependent, sustained reduction in blood pressure. There is no evidence of hypotension after the first dose, tachyphylaxis during long-term treatment, or withdrawal syndrome after discontinuation of treatment.
A single daily dose of olmesartan medoxomil provides effective and gentle blood pressure reduction over 24 hours. A single daily dose of the drug provides the same blood pressure reduction as when using its daily dose divided into 2 doses throughout the day.
With continuous treatment, the maximum reduction in blood pressure is achieved 8 weeks after the start of therapy, although a significant reduction in blood pressure is observed after 2 weeks of treatment. When used together with hydrochlorothiazide, an additional reduction in blood pressure is observed and such concomitant use of the drugs is well tolerated.
The effect of olmesartan on mortality and morbidity is still unknown.
The Olmesartan and Prevention of Microalbuminuria in Diabetes (ROADMAP) trial, which enrolled 4447 patients with type 2 diabetes, normoalbuminuria, and at least one cardiovascular risk factor, examined whether olmesartan treatment delayed the onset of microalbuminuria. During a follow-up study lasting a median of 3.2 years, patients received olmesartan or placebo in addition to other antihypertensive medications other than angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs).
By the criterion of clinical observations of the primary endpoint, the study demonstrated a significant reduction in the primary endpoint of prolongation of time to microalbuminuria in the olmesartan group.
After adjustment for blood pressure variability, this risk reduction was no longer statistically significant. Microalbuminuria developed in 8.2% (178 of 2160) of patients in the olmesartan group and in 9.8% (210 of 2139) of patients in the placebo group.
According to the clinical follow-up criteria for secondary endpoints, cardiovascular events occurred in 96 patients (4.3%) in the olmesartan group and 94 patients (4.2%) in the placebo group. The incidence of cardiovascular deaths was higher with olmesartan than with placebo [15 patients (0.7%) versus 3 patients (0.1%)], despite similar incidences of non-fatal stroke [14 patients (0.6%) versus 8 patients (0.4%)], non-fatal myocardial infarction [17 patients (0.8%) versus 26 patients (1.2%)], and deaths from other non-cardiovascular causes [11 patients (0.5%) versus 12 patients (0.5%)]. Overall mortality was numerically higher with olmesartan [26 patients (1.2%) versus 15 patients (0.7%)], which was mainly a result of a higher number of deaths due to cardiovascular disease.
The primary composite endpoint (time to first doubling of serum creatinine, end-stage renal disease, all-cause mortality) occurred in 116 patients in the olmesartan group (41.1%) and 129 patients in the placebo group (45.4%) [relative risk (RR) 0.97 (95% confidence interval (CI) 0.75–1.24); p = 0.791]. The secondary composite endpoint related to cardiovascular disease occurred in 40 patients in the olmesartan group (14.2%) and 53 patients in the placebo group (18.7%). This composite cardiovascular endpoint included cardiovascular death in 10 (3.5%) patients receiving olmesartan compared with 3 (1.1%) patients in the placebo group, overall mortality in 19 (6.7%) patients compared with 20 (7.0%) patients, non-fatal stroke in 8 (2.8%) patients compared with 11 (3.9%) patients, and non-fatal myocardial infarction in 3 (1.1%) patients compared with 7 (2.5%) patients, respectively.
Pediatric population
The antihypertensive effects of olmesartan medoxomil in the paediatric population were evaluated in a randomised, double-blind, placebo-controlled study involving 302 patients aged 6 to 17 years. The study group consisted of black patients (112 patients) and a mixed race group (190 patients) (38 of whom were black). The cause of hypertension was predominantly essential hypertension (87% of the black group and 67% of the mixed group). Patients weighing 20 to < 35 kg were randomized to receive 2.5 mg olmesartan medoxomil (low dose) or 20 mg (high dose) once daily, and patients weighing ≥ 35 kg were randomized to receive 5 mg (low dose) or 40 mg (high dose) once daily. Olmesartan medoxomil, at a dose adjusted for body weight, significantly reduced both systolic and diastolic blood pressure. Olmesartan medoxomil significantly reduced systolic blood pressure by 6.6 and 11.9 mm Hg (from baseline), respectively, at both the low and high doses. This effect was also observed during the 2-week withdrawal phase in the additional randomised groups, during which both mean systolic and diastolic blood pressure showed a statistically significant recovery in the placebo group compared with the olmesartan medoxomil group. In the paediatric population, treatment was effective in both primary and secondary hypertension. As in adults, blood pressure was reduced to a lesser extent in black children. In the same study, 59 patients aged 1 to 5 years and weighing ≥ 5 kg received 0.3 mg/kg olmesartan medoxomil once daily for 3 weeks in an open-label phase and were then randomised to either olmesartan medoxomil or placebo in a double-blind phase. At 2 weeks after discontinuation, mean systolic/diastolic blood pressure at trough was 3/3 mmHg lower in the olmesartan medoxomil randomised group; this difference in blood pressure was not statistically significant (95% CI -2 to 7/-1 to 7).
Other information
Two large randomized controlled trials, the ONTARGET study (a global endpoint study of telmisartan alone and in combination with ramipril) and the VA NEPHRON-D study (a study of diabetic nephropathy conducted by the US Department of Veterans Affairs), examined the use of a combination of ACE inhibitors with ARBs.
The ONTARGET study was conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus with signs of developing complications. The VA NEPHRON-D study was conducted in patients with type 2 diabetes mellitus and diabetic nephropathy.
These studies showed that, compared with monotherapy, the use of combination therapy did not lead to a significant beneficial effect on renal and/or cardiovascular outcomes and mortality, but caused an increased risk of hyperkalemia, acute kidney injury and/or hypotension. Given the similar pharmacodynamic properties of ACE inhibitors and ARBs II, the conclusions obtained are valid for other representatives of these drug categories. Thus, ACE inhibitors and ARBs II should not be used together in patients with diabetic nephropathy.
The ALTITUDE (Aliskiren in Type 2 Diabetes with Cardiovascular and Renal Endpoints) trial investigated the benefit of adding aliskiren to standard therapy with ACE inhibitors or ARBs in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. The trial was quickly stopped due to an increased risk of adverse events. Compared with placebo, patients in the aliskiren group had a numerically higher incidence of cardiovascular death and stroke, and related adverse events and serious adverse events (hyperkalemia, hypotension, and renal dysfunction) were also more common in patients in the aliskiren group.
Absorption and distribution.
Olmesartan medoxomil is a prodrug. It is rapidly converted to the pharmacologically active metabolite olmesartan by esterases in the intestinal mucosa and in the portal blood during absorption from the gastrointestinal tract.
No intact olmesartan medoxomil or unchanged side chain of the medoxomil group was detected in plasma or excretion products. The mean absolute bioavailability of olmesartan from the tablet formulation is 25.6%.
The mean maximum plasma concentration (Cmax) of olmesartan is reached approximately 2 hours after oral administration, and plasma concentrations increase almost linearly with increasing single oral doses up to 80 mg.
Food has virtually no effect on the bioavailability of olmesartan, so olmesartan medoxomil can be used regardless of meals.
No clinically significant gender differences were observed in the pharmacokinetics of olmesartan.
The binding of olmesartan medoxomil to plasma proteins is extensive (99.7%), but the potential for clinically significant shifts in protein binding when olmesartan is coadministered with other highly protein-bound medicinal products is low (as evidenced by the lack of clinically significant interactions between olmesartan medoxomil and warfarin). The binding of olmesartan to blood cells is negligible. The mean volume of distribution after intravenous administration is small (16–29 L).
Metabolism and excretion.
Total plasma clearance was generally 1.3 L/h (CL, 19%) and was relatively slow compared to hepatic circulation (approximately 90 L/h). Following a single oral dose of 14C-labeled olmesartan medoxomil, 10–16% of the administered radioactivity was excreted in the urine (the majority within 24 hours of dosing), with the remainder excreted in the faeces. Based on the systemic availability (25.6%), it can be estimated that absorbed olmesartan is eliminated both renally (approximately 40%) and via the liver and biliary tract (approximately 60%). All of the excreted radioactivity was identified as olmesartan. No other significant metabolite was identified. Enterohepatic recirculation of olmesartan is minimal. Since a significant proportion of olmesartan is excreted via the biliary tract, the use of the drug in patients with biliary obstruction is contraindicated (see section "Contraindications").
The terminal elimination half-life of olmesartan ranged from 10 to 15 hours after multiple oral administration. Steady state was achieved after the first few doses, with no further accumulation observed after 14 days of repeated dosing. Renal clearance was approximately 0.5–0.7 L/h and was independent of dose.
Pharmacokinetics in special patient groups.
Pediatric population
The pharmacokinetics of olmesartan were studied in hypertensive patients aged 1 to 16 years. Olmesartan clearance in these patients was similar to that in adult patients when adjusted for body weight.
There is no information on pharmacokinetics in pediatric patients with renal impairment.
Elderly people (65 years and older)
In hypertensive patients, the area under the concentration-time curve (AUC) at steady state was increased by approximately 35% in elderly patients (aged 65–75 years) and by approximately 44% in patients aged 75 years and older, compared with younger patients. This may be due, at least in part, to the average decrease in renal function in this patient group.
Kidney dysfunction
In patients with mild, moderate or severe renal impairment, steady-state AUC values increased by 62%, 82% and 179%, respectively, compared to those in healthy control volunteers (see sections 4.2 and 4.4).
Liver dysfunction
After a single oral dose, the AUC of olmesartan in patients with mild or moderate hepatic impairment was 6% and 65% higher, respectively, than in healthy volunteers. 2 hours after dosing, the unbound fraction of olmesartan in healthy volunteers and patients with mild and moderate hepatic impairment was 0.26%, 0.34% and 0.41%, respectively. After repeated dosing, the mean AUC of olmesartan in patients with moderate hepatic impairment was 65% higher than in healthy volunteers. The mean Cmax of olmesartan was similar in patients with hepatic impairment and in healthy volunteers. Olmesartan medoxomil has not been evaluated in patients with severe hepatic impairment (see sections 4.2 and 4.4).
Interaction with other drugs.
Colesevelam (bile acid sequestrant):
The half-life of olmesartan was reduced by 50-52%, regardless of whether it was administered simultaneously with colesevelam hydrochloride or 4 hours before the administration of this drug (see section “Interaction with other medicinal products and other forms of interaction”).
Preclinical safety data
In chronic toxicity studies in rats and dogs, the effects of olmesartan medoxomil were similar to other AT1 receptor antagonists and ACE inhibitors: increased blood urea (BUN) and creatinine (due to functional changes in the kidneys caused by AT1 receptor blockade), decreased heart weight, decreased red blood cell parameters (erythrocyte concentration, hemoglobin, hematocrit), and histological signs of kidney damage (foci of renal epithelial regeneration, thickening of the basement membrane, dilation of the renal tubules).
These undesirable effects, which are due to the pharmacological action of olmesartan medoxomil, have also occurred in preclinical studies with other AT1 receptor antagonists and ACE inhibitors and may be reduced by concomitant oral administration of sodium chloride.
Increased plasma renin activity and hypertrophy/hyperplasia of the juxtaglomerular cells of the kidneys were observed in both animal species. These changes, which are typical of the class of ACE inhibitors and other AT1 receptor antagonists, do not appear to be of clinical relevance.
Like other AT1 receptor antagonists, olmesartan medoxomil increases the frequency of chromosome breaks in cell culture in vitro. However, similar effects were not reproduced in several in vivo studies where olmesartan medoxomil was administered orally at very high doses, up to 2000 mg/kg. Overall, the data from a comprehensive genotoxicity study indicate that olmesartan is unlikely to be genotoxic in clinical use.
No carcinogenic effects of olmesartan were observed in a two-year study in rats and two six-month studies in transgenic mice.
In reproductive toxicity studies in rats, olmesartan medoxomil had no effect on fertility or was teratogenic. As with other angiotensin II receptor antagonists, offspring survival was reduced after exposure to olmesartan medoxomil, and dilatation of the renal pelvis was observed in dams treated late in pregnancy and during lactation. As with other antihypertensive drugs, olmesartan medoxomil was more toxic to pregnant rabbits than to pregnant rats, but was not fetotoxic.
Indication
Treatment of essential hypertension in adult patients.
Treatment of arterial hypertension in children and adolescents aged 6 to 18 years.
Contraindication
Hypersensitivity to the active substance or to one of the components of the medicinal product (see "Composition").
Pregnant women or women planning to become pregnant (see "Special instructions", "Use during pregnancy or breastfeeding").
Biliary tract obstruction (see "Pharmacokinetics").
The concomitant use of olmesartan medoxomil with aliskiren-containing products is contraindicated in patients with diabetes mellitus and renal insufficiency (glomerular filtration rate (GFR) < 60 ml/min/1.73 m2) (see Interactions with other medicinal products and other forms of interaction, Pharmacodynamics).
Interaction with other medicinal products and other types of interactions
Effects of other drugs on olmesartan medoxomil.
Other drugs with hypotensive effect
The hypotensive effect of olmesartan medoxomil may be increased when used concomitantly with other antihypertensive drugs.
ACE inhibitors, angiotensin II receptor blockers, or aliskiren
Dual blockade of the renin-angiotensin-aldosterone system (RAAS) through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher incidence of side effects such as hypotension, hyperkalemia and decreased renal function (including acute renal failure) compared with the separate use of drugs acting on the RAAS (see "Contraindications", "Special instructions for use", "Pharmacodynamics").
Potassium supplements and potassium-sparing diuretics
Concomitant use of drugs that act on the renin-angiotensin-aldosterone system with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that may increase potassium levels (e.g. heparin) may increase serum potassium levels, therefore such concomitant use is not recommended (see "Special warnings and precautions for use").
Nonsteroidal anti-inflammatory drugs (NSAIDs)
NSAIDs, including acetylsalicylic acid at a dose of more than 3 g per day, as well as COX-2 inhibitors and angiotensin II receptor antagonists, may act synergistically, reducing glomerular filtration. The simultaneous use of these drugs is associated with the risk of acute renal failure. In such cases, it is necessary to monitor renal function at the beginning of treatment and ensure adequate fluid intake in the patient's body.
Bile acid sequestrant colesevelam
Concomitant use of the bile acid sequestrant colesevelam hydrochloride reduces the systemic exposure to peak plasma concentrations of olmesartan and shortens its half-life. Administration of olmesartan medoxomil at least 4 hours before colesevelam hydrochloride reduces their interaction. Therefore, olmesartan medoxomil should be administered at least 4 hours before colesevelam hydrochloride (see Pharmacokinetics).
Other drugs
A modest decrease in the bioavailability of olmesartan medoxomil was observed after treatment with antacids (magnesium-aluminium hydroxide). Concomitant use with warfarin and digoxin did not affect the pharmacokinetics of olmesartan medoxomil.
Effect of olmesartan medoxomil on other medicinal products.
Lithium preparations
Concomitant use of lithium with angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists has been associated with reversible increases in serum lithium concentrations and increased toxicity of lithium preparations, and this combination is not recommended (see Precautions). If concomitant use proves necessary, careful monitoring of serum lithium concentrations is recommended in such patients during treatment.
Other drugs
No clinically significant interactions of olmesartan medoxomil with warfarin, digoxin, antacid (aluminium hydroxide/magnesium hydroxide), hydrochlorothiazide and pravastatin were observed. In particular, olmesartan medoxomil did not significantly affect the pharmacodynamics or pharmacokinetics of warfarin or the pharmacokinetics of digoxin.
Olmesartan medoxomil also had no clinically significant inhibitory effect on human cytochrome P450 enzymes 1A1/2, 2A6, 2C8/9, 2C19/2D6, 2E1, 3A4 and cytochrome P450 in vitro and minimal or no induced effect on cytochrome P450 in rats. Therefore, in vivo interaction studies with known inhibitors and inducers of cytochrome P450 enzymes have not been performed and no clinically significant interactions are expected between olmesartan and drugs metabolized by the above cytochrome P450 enzymes.
Pediatric population
Drug interaction studies with olmesartan medoxomil have only been conducted in adult patients. It is not known whether the interaction data are similar in adults and children.
Application features
Decreased circulating blood volume
Patients with reduced circulating blood volume and/or low serum sodium levels due to intensive diuretic therapy, dietary salt restriction, diarrhoea or vomiting may develop symptomatic hypotension, especially after the first dose of the medicinal product. Such changes should be corrected before initiating treatment with olmesartan medoxomil.
Other conditions associated with stimulation of the renin-angiotensin-aldosterone system
Patients whose vascular tone and function depend to a greater extent on the activity of the renin-angiotensin-aldosterone system, such as those with severe congestive heart failure or renal disease including renal artery stenosis, may respond to other drugs that affect this system with acute hypotension, azotemia, oliguria or, rarely, acute renal failure. The use of angiotensin II receptor antagonists may be associated with similar effects.
Vasorenal hypertension
The use of drugs that affect the renin-angiotensin-aldosterone system in patients with bilateral renal artery stenosis of a single functioning kidney is associated with the risk of severe hypotension and renal failure.
Kidney failure and kidney transplantation
In patients with renal impairment receiving olmesartan medoxomil, periodic monitoring of serum potassium and creatinine is recommended. The use of olmesartan medoxomil is not recommended in patients with severe renal impairment (creatinine clearance less than 20 ml/min) (see Dosage and Administration, Pharmacokinetics). There is no experience with the use of olmesartan medoxomil in patients who have recently undergone kidney transplantation or in patients with end-stage renal disease (creatinine clearance less than 12 ml/min).
Liver dysfunction
Olmesartan medoxomil is not recommended for use in patients with severe hepatic impairment due to lack of experience (see “Dosage and Administration” for dosing in mild and moderate hepatic impairment).
Hyperkalemia
Before prescribing concomitant medications that affect the renin-angiotensin-aldosterone system, the potential benefits and risks of this treatment should be carefully assessed and other therapeutic options should be considered (see also section “Dual blockade of the renin-angiotensin-aldosterone system (RAAS)”). The main risk factors for hyperkalemia include:
diabetes mellitus, renal dysfunction, patients over 70 years of age;
combination with one or more drugs that affect the renin-angiotensin-aldosterone system and/or with potassium preparations. Some drugs, even classes of drugs, can cause hyperkalemia: salt substitutes, potassium-containing drugs, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs, including selective COX-2 inhibitors, heparin, immunosuppressants, e.g. ciclosporin or tacrolimus, trimethoprim;
intercurrent diseases and conditions, including dehydration, acute cardiac decompensation, metabolic acidosis, increased severity of renal disorders, sudden renal dysfunction, e.g., in infectious diseases, cell lysis, e.g., in acute limb ischemia, rhabdomyolysis, polytrauma.
In patients with such risk factors, regular monitoring of serum potassium is recommended (see Interactions with other medicinal products and other forms of interaction).
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
There is evidence that the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS associated with the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see "Interaction with other medicinal products and other types of interactions", "Pharmacodynamics").
If dual blockade therapy is considered absolutely necessary, it should only be carried out under specialist supervision and with regular and careful monitoring of renal function, electrolyte levels and blood pressure.
ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
Lithium preparations
As with other angiotensin II receptor antagonists, the concomitant use of lithium with olmesartan medoxomil is not recommended (see Interaction with other medicinal products and other forms of interaction).
Aortic stenosis or mitral stenosis; obstructive hypertrophic cardiomyopathy
Olmesartan medoxomil should be used with caution in patients with aortic or mitral stenosis or obstructive hypertrophic cardiomyopathy.
Primary aldosteronism
Patients with primary aldosteronism do not respond to antihypertensive drugs that act through inhibition of the renin-angiotensin system. Therefore, the use of olmesartan medoxomil is not recommended in such patients.
Sprue-like enteropathy
In very rare cases, severe chronic diarrhoea with significant weight loss has been reported in patients taking olmesartan for a period of several months to a year after starting treatment, possibly due to a localised delayed-type hypersensitivity reaction. Intestinal biopsy of such patients has often shown villous atrophy. If a patient develops such symptoms during treatment with olmesartan, other aetiologies should be excluded. Discontinuation of olmesartan medoxomil should be considered unless another aetiology is identified. In cases where symptoms resolve and sprue-like enteropathy is confirmed by biopsy, olmesartan medoxomil should not be restarted.
Ethnic differences
As with all angiotensin II receptor antagonists, the antihypertensive effect of olmesartan medoxomil is somewhat less in black patients than in other patients, possibly because of a higher prevalence of low-renin states in this population.
Other
A significant decrease in blood pressure during treatment with any antihypertensive agents in patients with ischemic heart disease or cerebrovascular disease can lead to myocardial infarction and stroke.
The drug contains lactose, so it should not be used in patients with congenital galactose intolerance, congenital lactase deficiency or glucose-galactose malabsorption.
Use during pregnancy or breastfeeding
Cardosal® is contraindicated in pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment with Cardosal®, its use should be discontinued immediately and replaced with another drug approved for use in pregnant women. Epidemiological data on the risk of teratogenic effects of ACE inhibitors in the first trimester of pregnancy are not conclusive; however, a small increase in risk cannot be excluded. Although there are no controlled epidemiological data on the risk of angiotensin II receptor antagonists, similar risks may exist with this class of drugs. If long-term therapy with angiotensin II receptor antagonists is essential, patients planning to become pregnant are recommended to use other antihypertensive drugs that have an established safety profile for use in pregnancy. When pregnancy is diagnosed, angiotensin II receptor antagonists should be discontinued immediately and alternative treatment should be started. During the second and third trimesters, angiotensin II receptor antagonists are known to cause foetal (renal impairment, oligohydramnios, skull ossification retardation) and neonatal (renal failure, hypotension, hyperkalaemia) toxicity (see section 4.3). If angiotensin II receptor antagonists are used during the second and third trimesters, foetal renal function and skull ossification should be assessed by ultrasound. Infants whose mothers have taken angiotensin II receptor antagonists should be observed for hypotension (see sections 4.3 and 4.4).
Breast-feeding
Olmesartan has been shown to be excreted in rat milk, but there are no similar data in humans. Women who are breastfeeding should not use Cardosal® due to the lack of experience with its use during this period. Instead of Cardosal®, other antihypertensive drugs with proven safety during breastfeeding can be used, especially when feeding infants or premature infants.
Ability to influence reaction speed when driving vehicles or other mechanisms
Cardosal® has minor or moderate influence on the ability to drive and use machines. Dizziness or fatigue may occasionally occur in patients taking antihypertensive therapy, which may impair their ability to react.
Method of administration and doses
Adults
The initial daily dose of olmesartan medoxomil is 10 mg once daily. If blood pressure reduction is insufficient, the dose should be increased to 20 mg once daily. If necessary, the dose of the drug can be increased to 40 mg once daily (maximum daily dose) or hydrochlorothiazide can be added to the treatment.
The antihypertensive effect of olmesartan medoxomil is generally observed within 2 weeks of starting treatment, with the maximum effect occurring 8 weeks after starting therapy. This should be borne in mind when considering changing the dosage regimen for any patient.
Elderly patients (65 years and older)
No dose adjustment is usually necessary in elderly patients (see recommended doses for patients with renal impairment). When increasing the daily dose to the maximum of 40 mg, blood pressure should be closely monitored.
Patients with renal impairment
The maximum daily dose for patients with mild to moderate renal impairment (creatinine clearance 20-60 ml/min) is 20 mg, as there is no experience with higher doses in this group. Olmesartan medoxomil is not indicated in severe renal impairment (creatinine clearance less than 20 ml/min) due to limited experience in such patients (see sections 4.4 and 5.2).
Liver dysfunction
In patients with mild hepatic impairment, no dose adjustment is required. In patients with moderate hepatic impairment, the initial dose of olmesartan medoxomil is 10 mg/day, and the maximum dose is 20 mg. In patients with hepatic impairment, diuretics and/or other antihypertensive agents should be co-administered.
