CANDESARTAN/HYDROCHLOROTHIAZIDE

Posology in hypertension The recommended dose of Candesartan/Hydrochlorothiazide is one tablet once daily. Dose titration with the individual components (candesartan cilexetil and hydrochlorothiazide) is recommended. When clinically appropriate a direct change from monotherapy to Candesartan/Hydrochlorothiazide may be considered.

Dose titration of candesartan cilexetil is recommended when switching from hydrochlorothiazide monotherapy. Candesartan/Hydrochlorothiazide may be administered in patients whose blood pressure is not optimally controlled with candesartan cilexetil or hydrochlorothiazide monotherapy or Candesartan/Hydrochlorothiazide at lower doses.

Most of the antihypertensive effect is usually attained within 4 weeks of initiation of treatment. Special populations Elderly No dose adjustment is necessary in elderly patients. Intravascular volume depletion Dose titration of candesartan cilexetil is recommended in patients at risk for hypotension, such as patients with possible volume depletion (an initial dose of candesartan cilexetil of 4 mg may be considered in these patients).

73 m2 (BSA) a dose titration is recommended. 3). Hepatic impairment Dose titration of candesartan cilexetil is recommended in patients with mild to moderate chronic liver disease. 3). Paediatric population The safety and efficacy of Candesartan/Hydrochlorothiazide in children aged between birth and 18 years have not been established.

No data are available. Method of administration Oral use. Candesartan/Hydrochlorothiazide tablets can be taken with or without food. The bioavailability of candesartan is not affected by food. There is no clinically significant interaction between hydrochlorothiazide and food.

In controlled clinical studies with Candesartan /Hydrochlorothiazide adverse reactions were mild and transient. 3%). In clinical trials with Candesartan /Hydrochlorothiazide, adverse reactions were limited to those that were reported previously with candesartan cilexetil and/or hydrochlorothiazide.

The table below presents adverse reactions with candesartan cilexetil from clinical trials and post marketing experience. 8 are: - 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) System Organ Class Frequency Undesirable Effect Infections and infestations Common Respiratory infection Blood and lymphatic system disorders Very rare Leukopenia, neutropenia and agranulocytosis.

Metabolism and nutrition disorders Very rare Hyperkalaemia, hyponatraemia. Nervous system disorders Common Dizziness/vertigo, headache. Gastrointestinal disorders Not known Diarrhoea Hepatobiliary disorders Very rare Increased liver enzymes, abnormal hepatic function or hepatitis.

Skin and subcutaneous tissue disorders Very rare Angioedema, rash, urticaria, pruritus. Musculoskeletal and connective tissue disorders Very rare Back pain, arthralgia, myalgia. 4). The table below presents adverse reactions with hydrochlorothiazide monotherapy usually with doses of 25 mg or higher.

System Organ Class Frequency Undesirable Effect Neoplasms benign, malignant and unspecified (incl cysts and polyps) Not known Non-melanoma skin cancer (Basal cell carcinoma and Squamous cell carcinoma)1 Blood and lymphatic system disorders Rare Leukopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anaemia, bone marrow depression, haemolytic anaemia.

Immune system disorders Rare Anaphylactic reactions Metabolism and nutrition disorders Common Hyperglycaemia, hyperuricaemia, electrolyte imbalance (including hyponatraemia and hypokalaemia). Psychiatric disorders Rare Sleep disturbances, depression, restlessness.

Nervous system disorders Common Light-headedness, vertigo. Rare Paraesthesia. Eye disorders Rare Transient blurred vision. Not known Acute myopia, acute angle-closure glaucoma, choroidal effusion Cardiac disorders Rare Cardiac arrhythmias.

Vascular disorders Uncommon Postural hypotension. Rare Necrotising angiitis (vasculitis, cutaneous vasculitis). Rare Respiratory distress (including pneumonitis and pulmonary oedema). 4) Gastrointestinal disorders Uncommon Anorexia, loss of appetite, gastric irritation, diarrhoea, constipation.

Rare Pancreatitis. Hepatobiliary disorders Rare Jaundice (intrahepatic cholestatic jaundice). Skin and subcutaneous tissue disorders Uncommon Rash, urticaria, photosensitivity reactions. Rare Toxic epidermal necrolysis Not known Systemic lupus erythematosus, Cutaneous lupus erythematosus Musculoskeletal and connective tissue disorders Rare Muscle spasm.

Renal and urinary disorders Common Glycosuria. Rare Renal dysfunction and interstitial nephritis. General disorders and administration site conditions Rare Fever. Investigations Common Increases in cholesterol and triglycerides. Rare Increases in BUN and serum creatinine.

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

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.

3). Kidney transplantation There is limited clinical evidence regarding Candesartan/Hydrochlorothiazide use in patients who have undergone renal transplant. Renal artery stenosis Medicinal products that affect the renin-angiotensin-aldosterone system, including angiotensin II receptor antagonists (AIIRAs), may increase blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney.

Intravascular volume depletion In patients with intravascular volume and/or sodium depletion symptomatic hypotension may occur, as described for other agents acting on the renin-angiotensin-aldosterone system. Therefore, the use of Candesartan/Hydrochlorothiazide is not recommended until this condition has been corrected.

Anaesthesia and surgery Hypotension may occur during anaesthesia and surgery in patients treated with AIIRAs due to blockade of the renin-angiotensin system. Very rarely, hypotension may be severe such that it may warrant the use of intravenous fluids and/or vasopressors.

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 Candesartan/Hydrochlorothiazide 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 haemodynamically relevant aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy.

Primary hyperaldosteronism Patients with primary hyperaldosteronism generally will not respond to antihypertensive medicine sacting through inhibition of the renin-angiotensin-aldosterone system. Therefore the use of Candesartan/Hydrochlorothiazide is not recommended in this population.

Electrolyte imbalance Periodic determination of serum electrolytes should be performed at appropriate intervals. Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalance (hypercalcaemia, hypokalaemia, hyponatraemia, hypomagnesaemia and hypochloraemic alkalosis).

Thiazide diuretics may decrease the urinary calcium excretion and may cause intermittent and slightly increased serum calcium concentrations. Marked hypercalcaemia may be a sign of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.

Hydrochlorothiazide dose-dependently increases urinary potassium excretion which may result in hypokalaemia. This effect of hydrochlorothiazide seems to be less evident when combined with candesartan cilexetil. The risk for hypokalaemia may be increased in patients with cirrhosis of the liver, in patients experiencing brisk diuresis, in patients with an inadequate oral intake of electrolytes and in patients receiving concomitant therapy with corticosteroids or adrenocorticotropic hormone (ACTH).

Treatment with candesartan cilexetil may cause hyperkalaemia, especially in the presence of heart failure and/or renal impairment. g. heparin sodium, co-trimoxazole also known as trimethoprim/sulfamethoxazole) may lead to increases in serum potassium.

Monitoring of potassium should be undertaken as appropriate. Thiazides have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesaemia. Metabolic and endocrine effects Treatment with a thiazide diuretic may impair glucose tolerance.

Dose adjustment of antidiabetic medicines, including insulin, 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.

At the doses contained in Candesartan/Hydrochlorothiazide, only minimal effects were observed.. Thiazide diuretics increase serum uric acid concentration and may precipitate gout in susceptible patients. 8). If a photosensitivity reaction occurs, it is recommended to stop treatment.

If re-administration of treatment is essential, it is recommended to protect areas exposed to the sun or to artificial UVA radiation. g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with other medicinal products that affect this system including AIIRAs, has been associated with acute hypotension, azotaemia, oliguria or, rarely, acute renal failure.

As with any […]

1 or to sulfonamide derived active substances. Hydrochlorothiazide is a sulfonamide derived active substance. 6). 73 m2 BSA). - Severe hepatic impairment and/or cholestasis. - Refractory hypokalaemia and hypercalcaemia. - Gout. 1).