OLMESARTAN MEDOXOMIL/AMLODIPINE

Posology Adults The recommended dosage of Olmesartan medoxomil/Amlodipine is 1 tablet per day. Olmesartan medoxomil/Amlodipine 20 mg/5 mg may be administered in patients whose blood pressure is not adequately controlled by 20 mg olmesartan medoxomil or 5 mg amlodipine alone.

Olmesartan medoxomil/Amlodipine 40 mg/5 mg may be administered in patients whose blood pressure is not adequately controlled by Olmesartan medoxomil/Amlodipine 20 mg/5 mg. Olmesartan medoxomil/Amlodipine 40 mg/10 mg may be administered in patients whose blood pressure is not adequately controlled by Olmesartan medoxomil/Amlodipine 40 mg/5 mg.

A step-wise titration of the dosage of the individual components is recommended before changing to the fixed combination. When clinically appropriate, direct change from monotherapy to the fixed combination may be considered. For convenience, patients receiving olmesartan medoxomil and amlodipine from separate tablets may be switched to Olmesartan medoxomil/Amlodipine tablets containing the same component doses.

Olmesartan medoxomil/Amlodipine can be taken with or without food. 2). If up-titration to the maximum dose of 40 mg olmesartan medoxomil daily is required, blood pressure should be closely monitored. Renal impairment The maximum dose of olmesartan medoxomil in patients with mild to moderate renal impairment (creatinine clearance of 20 – 60 mL/min) is 20 mg olmesartan medoxomil once daily, owing to limited experience of higher dosages in this patient group.

2). Monitoring of potassium levels and creatinine is advised in patients with moderate renal impairment. 2). In patients with moderate hepatic impairment, an initial dose of 10 mg olmesartan medoxomil once daily is recommended and the maximum dose should not exceed 20 mg once daily.

Close monitoring of blood pressure and renal function is advised in hepatically-impaired patients who are already receiving diuretics and/or other antihypertensive agents. There is no experience of olmesartan medoxomil in patients with severe hepatic impairment.

As with all calcium antagonists, amlodipine's half-life is prolonged in patients with impaired liver function and dosage recommendations have not been established. Olmesartan medoxomil/Amlodipine should therefore be administered with caution in these patients.

5%). Adverse reactions from Olmesartan medoxomil/Amlodipine in clinical trials, post- authorisation safety studies and spontaneous reporting are summarised in the below table as well as adverse reactions from the individual components olmesartan medoxomil and amlodipine based on the known safety profile of these substances.

The following terminologies have been used in order to classify the occurrence of adverse reactions: Very common (≥1/10) Common (≥1/100 to <1/10) Uncommon (≥1/1,000 to <1/100) Rare (≥1/10,000 to <1/1,000) Very rare (<1/10,000), not known (cannot be estimated from the available data) FrequencyMedDRA System Organ Class Adverse reactions Olmesartan / Amlodipine combination Olmesartan Amlodipine Leukocytopenia Very rareBlood and lymphatic system disorders Thrombocytopenia Uncommon Very rare Allergic reaction /Drug hypersensitivity Rare Very rareImmune system disorders Anaphylactic reaction Uncommon Hyperglycaemia Very rare Hyperkalaemia Uncommon Rare Metabolism and nutrition disorders Hypertriglyceridaemia Common Hyperuricaemia Common Confusion Rare Depression Uncommon Insomnia Uncommon Irritability Uncommon Libido decreased Uncommon Psychiatric disorders Mood changes (including anxiety) Uncommon Dizziness Common Common Common Dysgeusia Uncommon Headache Common Common Common (especially at the beginning of treatment) Hypertonia Very rare Hypoaesthesia Uncommon Uncommon Lethargy Uncommon Paraesthesia Uncommon Uncommon Peripheral neuropathy Very rare Postural dizziness Uncommon Sleep disorder Uncommon Somnolence Common Syncope Rare Uncommon Tremor Uncommon Nervous system disorders Extrapyramidal disorder Not known Eye disorders Visual disturbance (including diplopia) Common Tinnitus UncommonEar and labyrinth disorders Vertigo Uncommon Uncommon Angina pectoris Uncommon Uncommon (incl.

4) Very rare Gastrointestinal disorders Intestinal angioedema Rare Hepatic enzymes increased Common Very rare (mostly consistent with cholestasis) Hepatitis Very rare Jaundice Very rare Hepato-biliary disorders Autoimmune hepatitis* Not known Alopecia Uncommon Angioneurotic oedema Rare Very rare Allergic dermatitis Uncommon Erythema multiforme Very rare Exanthema Uncommon Uncommon Exfoliative dermatitis Very rare Hyperhydrosis Uncommon Photosensitivity Very rare Pruritus Uncommon Uncommon Purpura Uncommon Quincke oedema Very rare Rash Uncommon Uncommon Uncommon Skin and subcutaneous tissue disorders Skin discoloration Uncommon Stevens-Johnson syndrome Very rare Toxic Epidermal Necrolysis Not known Urticaria Rare Uncommon Uncommon Ankle swelling Common Arthralgia Uncommon Arthritis Common Back pain Uncommon Common Uncommon Muscle spasm Uncommon Rare Common Myalgia Uncommon Uncommon Pain in extremity Uncommon Musculoskeletal and connective tissue disorders Skeletal pain Common Acute renal failure Rare Haematuria Common Increased urinary frequency Uncommon Micturition disorder Uncommon Nocturia Uncommon Pollakiuria Uncommon Renal insufficiency Rare Renal and urinary disorders Urinary tract infection Common Erectile dysfunction/impotence Uncommon UncommonReproductive system and breast disorders Gynecomastia Uncommon Asthenia Uncommon Uncommon Common Chest pain Common Uncommon Face oedema Rare Uncommon Fatigue Common Common Common Influenza-like symptoms Common Lethargy Rare Malaise Uncommon Uncommon Oedema Common Very common Pain Common Uncommon Peripheral oedema Common Common General disorders and administration site conditions Pitting oedema Common Blood creatinine increased Uncommon Rare Blood creatine phosphokinase increased Common Blood potassium decreased Uncommon Blood urea increased Common Investigations Blood uric acid increased Uncommon Gamma glutamyl transferase increased Uncommon Weight decrease Uncommon Weight increase Uncommon Single cases of rhabdomyolysis have been reported in temporal association with the intake of angiotensin II receptor blockers.

Patients with hypovolaemia or sodium depletion:

Symptomatic hypotension may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting, especially after the first dose. Correction of this condition prior to administration of Olmesartan medoxomil/Amlodipine or close medical supervision at the start of the treatment is recommended.

g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with other medicinal products that affect this system, such as angiotensin II receptor antagonists, has been associated with acute hypotension, azotaemia, oliguria or, rarely, acute renal failure.

Renovascular hypertension:

There is an increased risk of severe hypotension and 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- aldosterone system.

Renal impairment and kidney transplantation:

When Olmesartan medoxomil/Amlodipine is used in patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended. 2). e. creatinine clearance < 12 mL/min).

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, hyperkalaemia and decreased renal function (including acute renal failure). 1). If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.

6). 2). 1). Due to the component amlodipine Olmesartan medoxomil/Amlodipine is also contraindicated in patients with: - severe hypotension. - shock (including cardiogenic shock). g. high grade aortic stenosis). - haemodynamically unstable heart failure after acute myocardial infarction