Irbeplus HCT 300/12.5

Rx

Indications:

• For treatment of essential hypertension.
• In adult patients whose blood pressure is not adequately controlled on irbesartan or hydrochlorothiazide alone.

Dosage:

Adults:

• 1 tablet once daily.
• Dose titration with the individual components (i.e. irbesartan and hydrochlorothiazide) may be recommended.
• When clinically appropriate direct change from monotherapy to the fixed combinations may be considered:
  + Irbeplus HCT 150/12.5 may be administered in patients whose blood pressure is not adequately controlled with hydrochlorothiazide or irbesartan 150 mg alone.
  + Irbeplus HCT 300/12.5 may be administered in patients insufficiently controlled by irbesartan 300 mg or by Irbeplus HCT 150/12.5.
  + 300 mg irbesartan/25 mg hydrochlorothiazide fixed combination may be administered in patients insufficiently controlled by Irbeplus HCT 300/12.5.
• Doses higher than 300 mg irbesartan/25 mg hydrochlorothiazide once daily are not recommended.
• When necessary, Irbeplus HCT may be administered with another antihypertensive medicinal product.

Special populations:

• Renal impairment: Due to the hydrochlorothiazide component, Irbeplus HCT is not recommended for patients with severe renal dysfunction (creatinine clearance < 30 ml/min.
• Hepatic impairment: Irbeplus HCT is not indicated in patients with severe hepatic impairment. No dosage adjustment of Irbeplus HCT is necessary in patients with mild to moderate hepatic impairment.
• Older people: No dosage adjustment.
• Paediatric population: Irbeplus HCT is not recommended for use in children and adolescents.

Usage:

Irbeplus HCT is administered orally, with or without food.

• Hypersensitivity to any of the ingredients or to other sulfonamide-derived substances.
• Second and third trimesters of pregnancy.
• Severe renal impairment (creatinine clearance < 30 ml/min).
• Refractory hypokalaemia, hypercalcaemia.
• Severe hepatic impairment, biliary cirrhosis and cholestasis.
• Concomitant use with aliskiren-containing products in patients with diabetes mellitus or renal impairment (glomerular filtration rate (GFR) < 60 ml/min/1.73 m²).

Common:

• Increases in blood urea nitrogen (BUN), creatinine and creatine kinase,
• Dizziness, nausea/vomiting,
• Abnormal urination,
• Fatigue.

• Hypotension – Volume-depleted patients:
  Irbeplus HCT has been rarely associated with symptomatic hypotension in hypertensive patients without other risk factors for hypotension. Such conditions should be corrected before initiating therapy with Irbeplus HCT.
• 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.
• Renal impairment and kidney transplantation:
  When Irbeplus HCT is used in patients with impaired renal function, a periodic monitoring of potassium, creatinine and uric acid serum levels is recommended. In patients with mild to moderate renal impairment (creatinine clearance ≥ 30 ml/min but < 60 ml/min) Irbeplus HCT 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). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended. 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.
• Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy:
  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 Irbeplus HCT is not recommended.
• Metabolic and endocrine effects:
  Thiazide therapy may impair glucose tolerance. In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required. Latent diabetes mellitus may become manifest during thiazide therapy.
  Increases in cholesterol and triglyceride levels have been associated with thiazide diuretic therapy; however at the 12.5 mg dose contained in Irbeplus HCT, minimal or no effects were reported.
  Hyperuricaemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
• Electrolyte imbalance:
  Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalance (hypokalaemia, hyponatraemia, and hypochloremic alkalosis).
  Potassium-sparing diuretics, potassium supplements or potassium-containing salts substitutes should be co-administered cautiously with Irbeplus HCT.
  There is no evidence that irbesartan would reduce or prevent diuretic-induced hyponatraemia. Chloride deficit is generally mild and usually does not require treatment.
  Thiazides may decrease urinary calcium excretion and cause an intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.
  Thiazides have been shown to increase the urinary excretion of magnesium, which may result in hypomagnaesemia.
• Lithium:
  The combination of lithium and Irbeplus HCT is not recommended.
• Anti-doping test:
  Hydrochlorothiazide contained in Irbeplus HCT could produce a positive analytic result in an anti-doping test.
• General:
  In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system, treatment with angiotensin converting enzyme inhibitors or angiotensin-II receptor antagonists that affect this system has been associated with acute hypotension, azotaemia, oliguria, or rarely acute renal failure.
  Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history.
  Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazide diuretics.
  Cases of photosensitivity reactions have been reported with thiazides diuretics.
• Pregnancy:
  Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy. Unless continued AIIRA therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should be started.
• Acute myopia and secondary acute angle-closure glaucoma:
  Sulfonamide drugs or sulfonamide derivative drugs can cause an idiosyncratic reaction, resulting in transient myopia and acute angle-closure glaucoma. While hydrochlorothiazide is a sulfonamide, only isolated cases of acute angle-closure glaucoma have been reported so far with hydrochlorothiazide.
• Non-melanoma skin cancer:
  An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCTZ) exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry.
  Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC.
• Excipients:
  Irbeplus HCT contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
• Pregnancy:
  Irbeplus HCT is not recommended during the first trimester of pregnancy. A switch to a suitable alternative treatment should be carried out in advance of a planned pregnancy.
• Lactation:
  If Irbeplus HCT is used during breast feeding, doses should be kept as low as possible.
• Effects on ability to drive and use machines:
  When driving vehicles or operating machines, it should be taken into account that occasionally dizziness or weariness may occur during treatment of hypertension.