Olmesartan macleods 40
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- INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Olmesartan Macleods 10 / Olmesartan Macleods 10 Olmesartan Macleods 20 / Olmesartan Macleods 20 Olmesartan Macleods 40 / Olmesartan Macleods 40
- Composition:
- Pharmacological Properties
- Clinical characteristics.
- Special precautions for use.
- Dosage and Administration
- Adverse Reactions
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Olmesartan Macleods 10 / Olmesartan Macleods 10 Olmesartan Macleods 20 / Olmesartan Macleods 20 Olmesartan Macleods 40 / Olmesartan Macleods 40
Composition:
Active substance: olmesartan medoxomil;
One film-coated tablet contains olmesartan medoxomil 10 mg / 20 mg / 40 mg;
Excipients: microcrystalline cellulose; lactose monohydrate; hydroxypropylcellulose; magnesium stearate; colloidal anhydrous silicon dioxide; sodium starch glycolate (type B); coating "Instacoat Universal White A05G10022": hypromellose, hydroxypropylcellulose, talc, titanium dioxide (E 171).
Pharmaceutical form. Film-coated tablets.
Main physicochemical properties:
10 mg tablets: white, round, biconvex film-coated tablets, with engraving "С 52" on one side and smooth on the other side;
20 mg tablets: white, round, biconvex film-coated tablets, with engraving "C 53" on one side and smooth on the other side;
40 mg tablets: white, oval, biconvex film-coated tablets, with engraving "С 54" on one side and smooth on the other side.
Pharmacotherapeutic group.
Angiotensin II antagonists.
ATC code C09CA08.
Pharmacological Properties
Pharmacodynamics.
Olmesartan medoxomil is a selective angiotensin II receptor blocker (type AT1) intended for oral administration. Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldosterone system and plays a key role in the pathophysiology of arterial hypertension. It causes vasoconstriction, induces synthesis and secretion of aldosterone, stimulates cardiac activity, and promotes renal sodium reabsorption. Olmesartan inhibits the effects of angiotensin II on vasoconstriction and aldosterone secretion by blocking AT1 receptors in tissues, including vascular smooth muscle and adrenal glands. The action of olmesartan is independent of the source or pathway of angiotensin II synthesis. Selective binding of olmesartan to angiotensin II AT1 receptors leads to increased plasma renin levels and concentrations of angiotensin I and angiotensin II, as well as a slight reduction in plasma aldosterone concentration.
In patients with arterial hypertension, olmesartan medoxomil provides sustained, dose-dependent reduction in arterial blood pressure. No signs of arterial hypotension after first dose (first-dose effect), tachyphylaxis during prolonged use, or rebound hypertension after abrupt discontinuation of the drug have been observed.
Once-daily administration of olmesartan medoxomil provides effective and smooth reduction in arterial blood pressure over 24 hours until the next dose. When administered once daily, its antihypertensive effect was approximately equivalent to that achieved with twice-daily administration at the same total daily dose.
With continuous treatment, maximum reduction in arterial blood pressure is achieved within 8 weeks of initiating therapy; however, a significant antihypertensive effect is observed as early as 2 weeks after starting treatment.
The effect of olmesartan medoxomil on mortality and the incidence of complications has not been established.
The Randomized Olmesartan and Microalbuminuria Prevention in Type 2 Diabetes (ROADMAP) trial, involving 4447 patients with type 2 diabetes, normoalbuminuria, and at least one additional cardiovascular risk factor, was conducted to determine whether olmesartan therapy could delay the onset of microalbuminuria. During a mean follow-up period of 3.2 years, patients received either olmesartan or placebo in addition to other antihypertensive agents, except ACE inhibitors or ARBs.
In the primary endpoint of the study, a significant reduction in the risk of developing microalbuminuria was demonstrated with olmesartan treatment. However, after adjusting for differences in blood pressure levels, 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) in the placebo group.
In the secondary composite cardiovascular endpoint, events occurred in 96 patients (4.3%) receiving olmesartan and in 94 patients (4.2%) receiving placebo. Cardiovascular mortality was higher in the olmesartan group than in the placebo group (15 patients (0.7%) vs. 3 patients (0.1%)), despite similar rates of non-fatal stroke (14 patients (0.6%) vs. 8 patients (0.4%)), non-fatal myocardial infarction (17 patients (0.8%) vs. 26 patients (1.2%)), and non-cardiovascular mortality (11 patients (0.5%) vs. 12 patients (0.5%)). Overall mortality was numerically higher in the olmesartan group (26 patients (1.2%) vs. 15 patients (0.7%)), primarily due to higher cardiovascular mortality.
The ORIENT trial (Olmesartan Reducing Incidence of End-stage Renal Disease in Diabetic Nephropathy Trial) evaluated the effect of olmesartan on renal and cardiovascular outcomes in 577 randomized patients in Japan and China with type 2 diabetes and overt nephropathy. During a mean follow-up period of 3.1 years, patients received olmesartan or placebo in addition to other antihypertensive agents, including ACE inhibitors.
The primary composite endpoint (time to first occurrence of doubling of serum creatinine, end-stage renal disease, or all-cause mortality) was reached in 116 patients in the olmesartan group (41.1%) and in 129 patients receiving placebo (45.4%) (HR 0.97 (95% CI 0.75–1.24); p = 0.791). The secondary composite cardiovascular endpoint was reached in 40 patients receiving olmesartan (14.2%) and in 53 patients receiving placebo (18.7%). This composite cardiovascular endpoint included cardiovascular mortality in 10 (3.5%) patients receiving olmesartan and in 3 (1.1%) patients receiving placebo; overall mortality was 19 (6.7%) and 20 (7.0%), non-fatal stroke occurred in 8 (2.8%) and 11 (3.9%), and non-fatal myocardial infarction in 3 (1.1%) and 7 (2.5%), respectively.
Pharmacokinetics.
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 portal blood during absorption from the gastrointestinal tract.
Unhydrolyzed olmesartan medoxomil or unchanged medoxomil side chain have not been detected in plasma or excretory products. The mean absolute bioavailability of olmesartan in tablet form is 25.6%.
The mean peak plasma concentration (Cmax) of olmesartan medoxomil is reached approximately 2 hours after oral administration. Plasma concentrations increase nearly linearly with increasing single oral doses up to 80 mg.
Food has no clinically significant effect on the bioavailability of olmesartan; therefore, olmesartan medoxomil can be administered regardless of food intake.
No clinically significant differences in olmesartan pharmacokinetics based on gender have been observed.
Plasma protein binding of olmesartan medoxomil is 99.7%. However, the potential for clinically significant displacement due to interaction with other highly protein-bound drugs is low (supported by the absence of clinically significant interaction between olmesartan medoxomil and warfarin). Binding of olmesartan to blood cells is negligible. The mean volume of distribution after intravenous administration is small (16–29 L).
Metabolism and Elimination. Total plasma clearance is typically about 1.3 L/h (coefficient of variation (CV) 19%) and is relatively slow compared to hepatic blood flow (approximately 90 L/h). After a single oral dose of 14C-labeled olmesartan medoxomil, 10–16% of the administered radioactivity was excreted in urine (mostly within 24 hours after dose administration), and the remainder was recovered in feces. Based on a systemic availability of 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 recovered radioactivity was identified as olmesartan. No significant metabolites were detected. Enterohepatic recirculation of olmesartan is minimal.
The terminal elimination half-life of olmesartan ranges from 10 to 15 hours after multiple oral doses. Steady state is achieved after the first few doses. No accumulation was observed after 14 days of repeated administration. Renal clearance is approximately 0.5–0.7 L/h and is dose-independent.
Pharmacokinetics in Special Populations
Children. Olmesartan pharmacokinetics have been studied in children aged 1 to 16 years with hypertension. Olmesartan clearance in pediatric patients is similar to that in adults when adjusted for body weight.
There is no pharmacokinetic data available for children with renal impairment.
Elderly (aged 65 years and older). In patients with arterial hypertension, steady-state area under the concentration-time curve (AUC) increases by approximately 35% in patients aged 65–75 years and by approximately 44% in patients aged 75 years and older compared to younger patients. This may at least partly be related to reduced renal function in these patient groups.
Renal Impairment. In patients with mild, moderate, and severe renal impairment, steady-state AUC increases by 62%, 82%, and 179%, respectively, compared to healthy volunteers.
Hepatic Impairment. After a single oral dose, AUC values for olmesartan in patients with mild and moderate hepatic impairment were 6% and 65% higher, respectively, than in healthy volunteers. After repeated dosing in patients with moderate hepatic impairment, olmesartan AUC was 65% higher than in healthy volunteers. Mean Cmax values of olmesartan were similar in patients with hepatic impairment and in healthy volunteers. The effect of olmesartan medoxomil has not been evaluated in patients with severe hepatic impairment.
Clinical characteristics.
Indications.
Used for the treatment of:
- Essential hypertension in adults;
- Hypertension in children and adolescents aged 6 to 18 years.
Contraindications.
- Hypersensitivity to the active substance or to any of the excipients.
- Second and third trimesters of pregnancy.
- Biliary obstruction.
- Concomitant use of olmesartan medoxomil with products containing aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (glomerular filtration rate <60 mL/min/1.73 m²).
Special precautions.
Reduction in intravascular blood volume
In patients with volume and/or sodium depletion due to treatment with high-dose diuretics, dietary salt restriction, or diarrhea and/or vomiting, symptomatic hypotension may occur, primarily after the first dose of the medicinal product. Hypovolemia should be corrected prior to initiating treatment with olmesartan medoxomil.
Other conditions with stimulation of the renin-angiotensin-aldosterone system
In patients whose vascular tone and renal function primarily depend on the activity of the renin-angiotensin-aldosterone system (e.g., patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with other agents acting on this system has led to acute hypotension, azotemia, oliguria, and rarely, acute renal failure. Such outcomes cannot be excluded with angiotensin II receptor antagonists.
Renovascular hypertension
There is an increased risk of severe hypotension and renal failure in patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney when treated with medicinal products affecting the renin-angiotensin-aldosterone system.
Renal impairment and kidney transplantation
When olmesartan medoxomil is administered to patients with renal impairment, monitoring of serum potassium and creatinine levels is recommended. Olmesartan medoxomil is not recommended in patients with severe renal impairment (creatinine clearance <20 mL/min). 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 <12 mL/min).
Hepatic impairment
There is no experience with the use of olmesartan medoxomil in patients with severe hepatic impairment; therefore, its use is not recommended in this patient group.
Hyperkalemia
The use of medicinal products affecting the renin-angiotensin-aldosterone system may lead to hyperkalemia.
The risk of hyperkalemia, which may be fatal, is increased in elderly patients, patients with renal impairment, patients with diabetes mellitus, patients concomitantly taking other medicinal products that may increase potassium levels, and patients with intercurrent illnesses.
Prior to deciding on concomitant use of medicinal products affecting the renin-angiotensin-aldosterone system, the benefit-risk ratio should be assessed and alternative therapies considered.
The main risk factors for hyperkalemia are:
- Diabetes mellitus, renal impairment, age >70 years;
- Combination with other medicinal products affecting the renin-angiotensin-aldosterone system, or potassium supplements. Certain medicinal products or therapeutic classes may provoke hyperkalemia: potassium-containing salt substitutes, potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, nonsteroidal anti-inflammatory drugs (including selective cyclooxygenase (COX)-2 inhibitors), heparin, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim;
- Intercurrent illnesses, including dehydration, acute heart failure, metabolic acidosis, worsening renal function, sudden deterioration of kidney function (e.g., due to infections), cellular lysis (e.g., acute limb ischemia, rhabdomyolysis, extensive trauma).
Careful monitoring of serum potassium levels is recommended in patients at increased risk of hyperkalemia.
Lithium
Concomitant use of lithium with olmesartan medoxomil, as with other angiotensin II receptor antagonists, is not recommended.
Aortic or mitral valve stenosis / hypertrophic cardiomyopathy
Particular caution is required when prescribing olmesartan medoxomil, as with other vasodilators, to patients with aortic or mitral valve stenosis or obstructive hypertrophic cardiomyopathy.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism generally do not respond to antihypertensive agents acting via 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, patients taking olmesartan medoxomil have developed severe chronic diarrhea with substantial weight loss several months to a year after initiating treatment, possibly due to a localized delayed-type hypersensitivity reaction. Intestinal biopsy in these patients often shows villous atrophy. If a patient develops such symptoms during treatment with olmesartan medoxomil, other etiologies should be excluded. Olmesartan medoxomil should be discontinued if no other etiology is identified. If diarrhea symptoms do not resolve within one week after discontinuation of the medicinal product, medical advice should be sought.
Ethnic considerations
Like other angiotensin II receptor antagonists, olmesartan medoxomil may be less effective in reducing blood pressure in black patients compared to other patients, possibly due to a higher prevalence of low-renin conditions in black patients.
Other
Excessive reduction in blood pressure with any antihypertensive agent in patients with ischemic heart disease or cerebrovascular disease may lead to myocardial infarction or stroke.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
It has been demonstrated that concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure). Therefore, dual blockade of the RAAS by concomitant use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren is not recommended.
If dual blockade therapy is considered absolutely necessary, it should be administered only under specialist supervision with 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.
Olmesartan Macleods contains lactose. Patients with rare hereditary galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
Interaction with other medicinal products and other forms of interaction.
Potassium supplements and potassium-sparing diuretics
Based on experience with other agents affecting the renin-angiotensin system, concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other agents that may increase serum potassium levels (e.g., heparin) may lead to increased serum potassium levels. Therefore, such concomitant use is not recommended.
Other antihypertensive agents
The antihypertensive effect of olmesartan medoxomil may be enhanced by concomitant use of other antihypertensive agents.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Nonsteroidal anti-inflammatory medicinal products (including acetylsalicylic acid at doses >3 g/day and COX-2 inhibitors) and angiotensin II receptor antagonists may act synergistically by reducing glomerular filtration. Concomitant use of NSAIDs and angiotensin II receptor antagonists carries a risk of acute renal failure. Monitoring of renal function at the start of treatment and ensuring adequate fluid intake are recommended.
Additionally, concomitant use of NSAIDs may reduce the antihypertensive effect of angiotensin II receptor antagonists, leading to partial loss of efficacy.
Other substances
A moderate reduction in olmesartan bioavailability was observed after treatment with antacids (aluminum magnesium hydroxide). Concomitant administration of warfarin and digoxin had no effect on the pharmacokinetics of olmesartan.
Cholestyramine bile acid sequestrant
Concomitant use of the bile acid sequestrant colesevelam hydrochloride reduces the systemic exposure to peak plasma concentrations of olmesartan and shortens its elimination half-life. Administering olmesartan medoxomil at least 4 hours before colesevelam hydrochloride reduces this interaction. Therefore, olmesartan medoxomil should be administered at least 4 hours before colesevelam hydrochloride.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS)
Clinically, dual blockade of the renin-angiotensin-aldosterone system (RAAS) by combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren has been associated with a higher incidence of adverse effects, such as hypotension, hyperkalemia, and impaired renal function (including acute renal failure), compared to monotherapy with agents acting on the RAAS.
Effect of olmesartan medoxomil on other medicinal products
Lithium
Reversible increases in serum lithium concentrations and lithium toxicity have been observed during concomitant use of lithium with ACE inhibitors and angiotensin II receptor antagonists. Therefore, concomitant use of olmesartan medoxomil and lithium is not recommended. If such combination therapy is considered necessary, careful monitoring of serum lithium levels is recommended.
Other substances
No clinically significant interactions were observed with warfarin, digoxin, antacids (aluminum magnesium hydroxide), hydrochlorothiazide, and pravastatin. Specifically, olmesartan medoxomil had no significant effect on the pharmacokinetics or pharmacodynamics of warfarin or on the pharmacokinetics of digoxin.
In in vitro studies, olmesartan did not clinically significantly inhibit human cytochrome P450 enzymes 1A1/2, 2A6, 2C8/9, 2C19, 2D6, 2E1, and 3A4, and had no significant inducing effect on cytochrome P450 activity in animals. Therefore, in vivo studies on interactions with known inhibitors and inducers of cytochrome P450 enzymes were not conducted. No clinically significant interactions between olmesartan and medicinal products metabolized by the aforementioned cytochrome P450 enzymes are expected.
Children
Interaction studies have been conducted only in adults.
It is unknown whether interactions in children differ from those in adults.
Special precautions for use.
Intestinal angioedema
Cases of intestinal angioedema have been reported in patients taking angiotensin II receptor antagonists, [including olmesartan medoxomil] (see section "Adverse reactions"). These patients experienced abdominal pain, nausea, vomiting, and diarrhea. Symptoms resolved after discontinuation of angiotensin II receptor antagonists. If intestinal angioedema is diagnosed, Olmesartan Mylan should be discontinued and appropriate monitoring initiated until symptoms completely resolve.
Use during pregnancy or breastfeeding
Pregnancy. Use of angiotensin II antagonists is not recommended during the first trimester of pregnancy. Use of angiotensin II antagonists is contraindicated during the second and third trimesters of pregnancy.
Epidemiological evidence regarding teratogenic risk associated with angiotensin-converting enzyme (ACE) inhibitors during the first trimester of pregnancy has not been conclusive; however, a slight increase in risk cannot be excluded. As there are no controlled epidemiological data on the teratogenicity of angiotensin II antagonists, similar risks cannot be ruled out.
Women planning pregnancy should have their treatment with angiotensin II receptor blockers replaced with alternative antihypertensive therapies with an established safety profile during pregnancy, unless continuation of such therapy is considered essential. If pregnancy is diagnosed, treatment with angiotensin II antagonists should be stopped immediately, and alternative therapy should be initiated if necessary.
It is known that use of angiotensin II antagonists during the second and third trimesters of pregnancy causes fetal toxicity in humans (reduced renal function, oligohydramnios, delayed skull ossification) and neonatal toxicity (renal failure, hypotension, hyperkalemia).
If exposure to angiotensin II antagonists occurred during the second trimester of pregnancy, ultrasound evaluation of renal function and skull development is recommended. Infants born to mothers who took angiotensin II antagonists during pregnancy should be closely monitored for hypotension.
Lactation. Olmesartan is excreted in rat milk; however, it is unknown whether olmesartan is excreted in human milk. Due to lack of information on the use of olmesartan medoxomil during breastfeeding, the medicinal product is not recommended for use in nursing mothers. Alternative treatments with an established safety profile during breastfeeding are preferred, especially when breastfeeding a newborn or preterm infant.
Ability to affect the speed of reactions when driving or operating machinery
Olmesartan has a minor or moderate influence on the ability to drive or operate machinery. Dizziness or fatigue may occasionally occur in patients receiving antihypertensive therapy, which may impair reaction speed.
Dosage and Administration
It is recommended to take olmesartan medoxomil tablets approximately at the same time each day, with or without food, for example, during breakfast. The tablet should be swallowed with sufficient liquid (e.g., one glass of water). The tablet must not be chewed.
Adults
The recommended initial dose of olmesartan medoxomil is 10 mg once daily. For patients in whom blood pressure is not adequately controlled at this dose, the dose of olmesartan medoxomil may be increased to the optimal dose of 20 mg once daily. If additional blood pressure reduction is required, the dose of olmesartan medoxomil may be increased up to a maximum of 40 mg daily or hydrochlorothiazide therapy may be added.
The antihypertensive effect of olmesartan medoxomil is usually apparent within 2 weeks of starting treatment and reaches a maximum after approximately 8 weeks of treatment. This should be taken into account when considering a dose adjustment regimen for any patient.
Elderly (over 65 years of age)
Dosage adjustment is generally not required for elderly patients. If an increase to the maximum dose of 40 mg daily is needed, blood pressure should be carefully monitored.
Renal impairment
The maximum dose for patients with mild to moderate renal impairment (creatinine clearance 20–60 mL/min) is 20 mg of olmesartan medoxomil once daily due to limited experience with higher doses in this patient group.
The use of olmesartan medoxomil in patients with severe renal impairment (creatinine clearance <20 mL/min) is not recommended, as there is only limited experience in this patient group.
Hepatic impairment
Dosage adjustment is not required in patients with mild hepatic impairment. In patients with moderate hepatic impairment, the recommended initial dose is 10 mg of olmesartan medoxomil once daily, and the maximum dose should not exceed 20 mg once daily. Careful monitoring of blood pressure and renal function is recommended in patients with hepatitis who are already receiving diuretics and/or other antihypertensive agents. There is no experience with olmesartan medoxomil treatment in patients with severe hepatic impairment; therefore, use of the medicinal product is not recommended in this patient group. Olmesartan medoxomil must not be used in patients with biliary obstruction.
Children
Patients aged 6 to 18 years. The recommended initial dose of olmesartan medoxomil for children aged 6 years and older is 10 mg of olmesartan medoxomil once daily. In children whose blood pressure is not adequately controlled at this dose, the dose of olmesartan medoxomil may be increased to 20 mg once daily. If additional blood pressure reduction is required, the dose of olmesartan medoxomil may be increased up to a maximum of 40 mg daily in children with body weight ≥35 kg. For children with body weight <35 kg, the daily dose must not exceed 20 mg.
Other pediatric patients. Olmesartan medoxomil must not be used in children under 6 years of age due to safety concerns and lack of data in this age group.
Overdose
Only limited information on overdose in humans is available. The most likely manifestation of overdose is arterial hypotension. In case of overdose, close monitoring of the patient is required, and treatment should be symptomatic and supportive.
There is no data on removal of olmesartan medoxomil by dialysis.
Adverse Reactions
The adverse reactions most commonly observed during treatment with olmesartan medoxomil are headache (7.7%), influenza-like symptoms (4.0%), and dizziness (3.7%).
In placebo-controlled monotherapy trials, dizziness was the only treatment-related adverse reaction (incidence 2.5% with olmesartan medoxomil versus 0.9% in the placebo group).
The frequency of laboratory parameter abnormalities was slightly higher with olmesartan medoxomil compared to placebo: hypertriglyceridemia — 2.0% with olmesartan medoxomil versus 1.1% with placebo; increased creatine phosphokinase levels — 1.3% with olmesartan medoxomil versus 0.7% with placebo.
Unwanted effects identified from clinical trials of olmesartan medoxomil, post-marketing safety studies, and spontaneous reports are listed in the table. Adverse reactions are categorized by frequency as follows: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency not known (cannot be estimated from available data).
| Organ systems by MedDRA classification |
Adverse reactions |
Frequency |
| Blood and lymphatic system disorders |
Thrombocytopenia |
Uncommon |
| Immune system disorders |
Anaphylactic reaction |
Uncommon |
| Metabolism and nutrition disorders |
Hypertriglyceridemia |
Common |
| Hypercholesterolemia |
Uncommon |
|
| Hyperuricemia |
Common |
|
| Hyperkalemia |
Rare |
|
| Nervous system disorders |
Dizziness |
Common |
| Headache |
Common |
|
| Ear and labyrinth disorders |
Vertigo |
Uncommon |
| Cardiac disorders |
Angina pectoris |
Uncommon |
| Tachycardia |
Uncommon |
|
| Vascular disorders |
Arterial hypotension |
Rare |
| Respiratory, thoracic and mediastinal disorders |
Bronchitis |
Common |
| Pharyngitis |
Common |
|
| Cough |
Common |
|
| Rhinitis |
Common |
|
| Hepatobiliary disorders |
Autoimmune hepatitis* |
Not known |
| Gastrointestinal disorders |
Gastroenteritis |
Common |
| Diarrhea |
Common |
|
| Abdominal pain |
Common |
|
| Nausea |
Common |
|
| Dyspepsia |
Common |
|
| Vomiting |
Uncommon |
|
| Intestinal angioedema |
Rare |
|
| Sprue-like enteropathy (see "Special precautions") |
Very rare |
|
| Skin and subcutaneous tissue disorders |
Exanthema |
Uncommon |
| Allergic dermatitis |
Uncommon |
|
| Urticaria |
Uncommon |
|
| Rash |
Uncommon |
|
| Pruritus |
Uncommon |
|
| Alopecia |
Not known |
|
| Angioedema |
Rare |
|
| Musculoskeletal and connective tissue disorders |
Arthritis |
Common |
| Back pain |
Common |
|
| Bone pain |
Common |
|
| Myalgia |
Uncommon |
|
| Arthralgia |
Uncommon |
|
| Muscle cramps |
Rare |
|
| Renal and urinary disorders |
Hematuria |
Common |
| Urinary tract infection |
Common |
|
| Acute renal failure |
Rare |
|
| Renal function impairment |
Rare |
|
| General disorders |
Pain |
Common |
| Chest pain |
Common |
|
| Peripheral edema |
Common |
|
| Influenza-like symptoms |
Common |
|
| Increased fatigue |
Common |
|
| Facial swelling |
Uncommon |
|
| Asthenia |
Uncommon |
|
| Malaise |
Uncommon |
|
| Lethargic state |
Rare |
|
| Changes in laboratory parameters |
Elevated liver enzymes |
Common |
| Elevated blood urea levels |
Common |
|
| Elevated creatine phosphokinase levels in blood |
Common |
|
| Elevated creatinine levels in blood |
Rare |
*Cases of autoimmune hepatitis with a latency period ranging from several months to years have been reported in the post-marketing period, which were reversible upon discontinuation of olmesartan.
Isolated cases of rhabdomyolysis, temporally associated with angiotensin II receptor blockers, have been reported.
Special patient groups
Paediatric population
During two clinical studies involving children and adolescents (361 subjects) aged 1 to 17 years, safety monitoring of olmesartan medoxomil was conducted. While the nature and severity of adverse reactions were similar to those observed in adult patients, the frequency of the following adverse reactions was higher in children than in adults:
−Nasal bleeding is a common adverse reaction (from ≥ 1/100 to < 1/10) in children, which was not observed in adult patients;
−During the 3-week double-blind study, the incidence of dizziness and headache requiring treatment was nearly twice as high in children aged 6 to 17 years in the group receiving high-dose olmesartan medoxomil.
Overall, the safety profile of olmesartan medoxomil in paediatric patients did not differ significantly from that in adult patients.
Elderly patients (aged 65 years and older)
Hypotension may occur somewhat more frequently in elderly patients ("rarely" or "uncommonly").
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions is important after marketing authorization of the medicinal product. This allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions.
Shelf life.
3 years.
Storage conditions.
Store at a temperature not exceeding 25 °C in the original packaging. Keep out of reach of children.
Packaging.
10 tablets per blister, 3 or 9 blisters per cardboard pack.
Prescription status. Prescription only.
Manufacturer.
Macleods Pharmaceuticals Limited.
Manufacturer's address and place of business.
Village Thedda, P.O. Lodhiamaira, Tehsil Baddi, District Solan, Himachal Pradesh, 174101, India.