OLMESARTAN MEDOXOMIL AMLODIPINE AND HYDROCHLOROTHIAZIDE

The safety of Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide was investigated in clinical trials in 7826 patients receiving olmesartan medoxomil in combination with amlodipine and hydrochlorothiazide. Adverse reactions from clinical trials, post-authorization safety studies and spontaneous reporting are summarized in table 1 for Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide as well as for the individual components olmesartan medoxomil, amlodipine and hydrochlorothiazide based on the known safety profile of the single components.

The most commonly reported adverse reactions during treatment with Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide are peripheral oedema, headache and dizziness. 4) Not known Choroidal Effusion Not known Vertigo Uncommon Uncommon RareEar and labyrinth disorders Tinnitus Uncommon Palpitations Common Common Tachycardia Uncommon Myocardial infarction Very rare Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) Uncommon Rare Cardiac disorders Angina pectoris Uncommon Uncommon (incl.

4) Very rare Gastrointestinal disorders Intestinal angioedema Rare Hepatitis Very rare Jaundice (intrahepatic cholestatic icterus) Very rare Rare Acute cholecystitis Rare Hepato-biliary disorders Autoimmune Not known hepatitis* Alopecia Uncommon Angioedema Rare Very rare Allergic dermatitis Uncommon Erythema multiforme Very rare Erythema Uncommon Cutaneous lupus erythematodes -like reactions Rare Exanthema Uncommon Uncommon Exfoliative dermatitis Very rare Hyperhydrosis Uncommon Photosensitivi ty reactions Very rare Uncommon Pruritus Uncommon Uncommon Uncommon Purpura Uncommon Uncommon Quincke oedema Very rare Rash Uncommon Uncommon Uncommon Reactivation of cutaneous lupus erythematodes Rare Toxic epidermal necrolysis Not known Rare Skin discoloration Uncommon Stevens- Johnson syndrome Very rare Skin and subcutaneous tissue disorders Urticaria Uncommon Uncommon Uncommon Muscle spasm Common Rare Common Joint swelling Common Muscular weakness Uncommon Rare Ankle swelling Common Arthralgia Uncommon Arthritis Common Back pain Common Uncommon Musculoskeletal and connective tissue disorders Paresis Rare Myalgia Uncommon Uncommon Skeletal pain Common Pollakiuria Common Increased urinary frequency Uncommon Acute renal failure Rare Haematuria Common Micturition disorder Uncommon Nocturia Uncommon Interstitial nephritis Rare Renal and urinary disorders Renal insufficiency Rare Rare Erectile dysfunction Uncommon Uncommon […]

8). These patients presented with abdominal pain, nausea, vomiting and diarrhoea. Symptoms resolved after discontinuation of angiotensin II receptor antagonists. If intestinal angioedema is diagnosed, Olmesartan should be discontinued and appropriate monitoring should be initiated until complete resolution of symptoms has occurred.

Patients with hypovolaemia or sodium depletion:

Symptomatic hypotension may occur in patients who are volume and/or sodium depleted as a result of 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 and Hydrochlorothiazide or close medical supervision at the start of the treatment is recommended.

Other conditions with stimulation of the renin-angiotensin-aldosterone system:

In patients whose vascular tone and renal function depend predominantly 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 medicinal products that affect this system 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 and Hydrochlorothiazide is used in patients with impaired renal function, periodic monitoring of serum concentrations of potassium and creatinine is recommended. 2). Thiazide diuretic-associated azotaemia may occur in patients with impaired renal function.

If progressive renal impairment becomes evident, careful reappraisal of therapy is necessary, with consideration given to discontinuing diuretic therapy. There is no experience of the administration of Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide in patients with a recent kidney transplant or in patients with end-stage renal impairment (i.

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.

ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. 2). Furthermore, minor alterations of fluid and electrolyte balance during thiazide therapy may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.

Care should be taken when Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide is administered in patients with mild to moderate hepatic impairment. 2). In patients with impaired hepatic function, amlodipine should be initiated at the lower end of the dosing range and caution should be used, both on initial treatment and when increasing the dose.

3).

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy:

Due to the amlodipine component of Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide, as with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.

Primary aldosteronism:

Patients with primary aldosteronism generally will not respond to anti-hypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide is not recommended in such patients.

Metabolic and endocrine effects:

Thiazide therapy may impair glucose tolerance. 5). Latent diabetes mellitus may become manifest during thiazide therapy. Increases in cholesterol and triglyceride levels are undesirable effects known to be associated with thiazide diuretic therapy.

Hyperuricaemia may occur or frank gout may be precipitated in some patients receiving thiazide therapy.

Electrolyte imbalance:

As for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals. Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalance (including hypokalaemia, hyponatraemia and hypochloraemic alkalosis).

Warning signs of fluid or electrolyte imbalance are dryness of the mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscle […]

1. 2). Refractory hypokalaemia, hypercalcaemia, hyponatraemia and symptomatic hyperuricaemia. 2). 6). 1). Due to the amlodipine component, Olmesartan Medoxomil, Amlodipine and Hydrochlorothiazide is contraindicated in patients with: - Shock (including cardiogenic shock).

- Severe hypotension. g. high grade aortic stenosis). - Haemodynamically unstable heart failure after acute myocardial infarction.