IRBESARTAN/HYDROCHLOROTHIAZIDE MYLAN

Posology Irbesartan/Hydrochlorothiazide Mylan can be taken once daily. e. irbesartan and hydrochlorothiazide) may be recommended. 5 mg. 5 mg. Doses higher than 300 mg irbesartan/25 mg hydrochlorothiazide once daily are not recommended. 1).

Special Populations Renal impairment:

Due to the hydrochlorothiazide component, Irbesartan/Hydrochlorothiazide Mylan is not recommended for patients with severe renal dysfunction (creatinine clearance < 30 ml/min). Loop diuretics are preferred to thiazides in this population.

4).

Hepatic impairment:

Irbesartan/Hydrochlorothiazide Mylan is not indicated in patients with severe hepatic impairment. Thiazides should be used with caution in patients with impaired hepatic function. 3).

Elderly:

No dosage adjustment of Irbesartan/Hydrochlorothiazide Mylan is necessary in elderly.

Paediatric population:

Irbesartan/Hydrochlorothiazide Mylan is not recommended for use in children and adolescents because the safety and efficacy have not been established. No data are available. Method of administration For oral use. Irbesartan/Hydrochlorothiazide Mylan may be taken with or without food.

5% of the patients experienced adverse reactions. 4%). 1 %) were also commonly observed in the trials. Table 1 gives the adverse reactions observed from spontaneous reporting and in-placebo-controlled trials. The frequency of adverse reactions listed below is defined using the following convention: • 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) Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. 4) Reproductive system and breast disorders Uncommon: sexual dysfunction, libido changes General disorders and administration site conditions: Common: fatigue Common: increases in blood urea nitrogen (BUN), creatinine and creatinine kinase Investigations: Uncommon: decreases in serum potassium and sodium Additional information on individual components: In addition to the adverse reactions listed above for the combination product, other adverse reactions previously reported with one of the individual components may be potential adverse reactions with Irbesartan/Hydrochlorothiazide Mylan.

Tables 2 and 3 below detail the adverse reactions reported with the individual components. 4), hyperuricaemia, glycosuria, hyperglycaemia, increases in cholesterol and triglycerides The dose dependent adverse events of hydrochlorothiazide (particularly electrolyte disturbances) may increase when titrating the hydrochlorothiazide.

1). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

Acute Respiratory Toxicity Very rare severe cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS) have been reported after taking hydrochlorothiazide. Pulmonary oedema typically develops within minutes to hours after hydrochlorothiazide intake.

At the onset, symptoms include dyspnoea, fever, pulmonary deterioration and hypotension. If diagnosis of ARDS is suspected, Irbesartan/Hydrochlorothiazide Mylan should be withdrawn and appropriate treatment given. Hydrochlorothiazide should not be administered to patients who previously experienced ARDS following hydrochlorothiazide intake.

Hypotension-Volume-depleted patients:

Irbesartan/hydrochlorothiazide tablets have been rarely associated with symptomatic hypotension in hypertensive patients without other risk factors for hypotension. Symptomatic hypotension may be expected to occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting.

Such conditions should be corrected before initiating therapy with Irbesartan/Hydrochlorothiazide Mylan.

Renal artery stenosis - 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 angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists.

While this is not documented with irbesartan/hydrochlorothiazide tablets, a similar effect should be anticipated.

Renal impairment and kidney transplantation:

When Irbesartan/Hydrochlorothiazide Mylan is used in patients with impaired renal function, a periodic monitoring of potassium, creatinine and uric acid serum levels is recommended. There is no experience regarding the administration of irbesartan/hydrochlorothiazide tablets in patients with a recent kidney transplantation.

3). Thiazide diuretic-associated azotaemia may occur in patients with impaired renal function. No dosage adjustment is necessary in patients with renal impairment whose creatinine clearance is ≥ 30 ml/min. However, in patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml/min but < 60 ml/min) this fixed dose combination should be administered with caution.

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.

Hepatic impairment:

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. There is no clinical experience with Irbesartan/Hydrochlorothiazide Mylan in patients with hepatic impairment.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy:

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 antihypertensive medicinal products acting through inhibition of the renin- angiotensin system. Therefore, the use of Irbesartan/Hydrochlorothiazide Mylan is not recommended.

Metabolic and endocrine effects:

Thiazide therapy may impair glucose tolerance Latent diabetes mellitus may become manifest during thiazide therapy. Irbesartan may induce hypoglycaemia, particularly in diabetic patients. 5). 5 mg dose contained in irbesartan/hydrochlorothiazide tablets, minimal or no effects were reported.

Hyperuricaemia may occur or frank gout may be precipitated in certain 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 (hypokalaemia, hyponatraemia, and hypochloraemic alkalosis).

Warning signs of fluid or electrolyte imbalance are dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea or vomiting.

Although hypokalaemia may develop with the use of thiazide diuretics, concurrent therapy with irbesartan may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greatest in patients with cirrhosis of the liver, in patients experiencing brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes and in patients receiving concomitant therapy with corticosteroids or ACTH.

Conversely, due to the irbesartan component of Irbesartan/Hydrochlorothiazide Mylan hyperkalaemia might occur, especially in the presence of renal impairment and/or heart failure, and diabetes mellitus. […]

1).