Safebul® 8 mg tablets.  Each tablet contains 8 mg of candesartan cilexetil.  Safebul® 16 mg tablets.  Each tablet contains 16 mg of candesartan cilexetil and Safebul® 32 mg tablets.  Each tablet contains 32 mg of candesartan cilexetil. Excipients with known effect: lactose monohydrate. Therapeutic indications. Essential hypertension in adult patients.  Hypertension treatment in children and adolescents between 6 and  ˂18 years of age.  Adult patients with heart failure and impaired left ventricular systolic function  (left ventricular ejection fraction ≤ 40%),  when angiotensin-converting enzyme inhibitors  (ACE inhibitors) are not tolerated or as combination  therapy with  an ACE inhibitor in patients with symptomatic heart failure, despite optimal therapy, or when  mineralocorticoid receptor antagonists are not tolerated.  Posology.  Hypertension:  the recommended starting dose and the usual maintenance dose is 8 mg once daily. The dose may be increased up to 16 mg once daily. If your blood pressure is not sufficiently controlled after 4 weeks of treatment with 16 mg once daily and up to a maximum of 32 mg once daily. Treatment should be adjusted according to the blood pressure response. Safebul® can also be administered with other antihypertensive agents. The addition of hydrochlorothiazide has  shown an additive antihypertensive effect with various Safebul® dosages.   Use in older adults: no need to adjust the starting dose in these patients. Use in patients with intravascular volume reduction: an initial dose of 4 mg can be considered in patients at risk of hypotension, such as patients with possible volume depletion. Use in patients with renal impairment: the starting dose is 4 mg in patients with renal impairment, including patients on haemodialysis. The dose should be adjusted according to the response. There is limited experience in patients with very severe or end-stage renal impairment (Cl_creatinine< 15 ml / min). Use in hepatic impairment: an initial dose of 4 mg is recommended once daily in patients with mild to moderate hepatic impairment. The dose may be adjusted according to the response. Safebul® is contraindicated in patients with severe hepatic impairment and/or cholestasis.  Use in black patients:  the antihypertensive effect of Safebul® is less pronounced in black patients than in patients of other races, as a result, dose adjustment of Safebul® and the use of a concomitant therapy may be more frequently necessary  to  control  blood pressure in black patients than in patients of other races. Use in the pediatric population: children and adolescents between 6 and <18 years of age, the recommended starting dose is 4 mg once daily. For patients weighing  <50 kg in whom blood pressure is not adequately controlled, the dose can be increased to a maximum of 8 mg once daily. For patients weighing  >50 kg, in whom blood pressure is not adequately controlled, the dose can be increased to 8 mg once daily and then if it is required up to 16 mg once daily.  Doses over 32 mg have not been studied in pediatric patients.  Safebul® has not been studied in children with glomerular filtration rate less than 30 mL/min/1.73m². Black pediatric patients: the antihypertensive effect of Safebul® is less pronounced in black patients than in non-black patients. Children between 1 and < 6 years of age: safety and efficacy have not been established in children between 1 and 6 years of age. Safebul® is contraindicated in children younger than 1 year.  Dosage in heart failure: the usual recommended starting dose of Safebul® is 4 mg once daily. Adjustment up to the desired dose of 32 mg once daily (maximum dose) or up to the maximum tolerated dose is done by doubling the dose at intervals of at least 2 weeks.   Safebul® may be given with other treatment for heart failure,  including ACE inhibitors,  beta blockers, diuretics and digitalis or a combination of these drugs. Safebul® can be administered in conjunction with an ACE inhibitor in patients with symptomatic heart failure despite optimal standard therapy for heart failure when a mineralocorticoid receptor antagonist is not tolerated.  Contraindications:  hypersensitivity to Safebul® active substance or to any of the excipients. Pregnancy. Severe hepatic impairment and/or cholestasis. Concomitant use of angiotensin II receptor antagonists (ARAIIs), including Safebul® or an ACE inhibitor with aliskiren in patients with type 2 diabetes. Children under 1 year of age.  Precautions for use: renal impairment.  As with other renin inhibitors - angiotensin – aldosterone (RAAS), changes in renal function can be expected in sensitive patients treated with Safebul®.  Use in pediatric patients, including patients with renal impairment: Safebul® has not been studied in children with a glomerular filtration rate of less than 30 mL/min/1.73m².   For children with possible intravascular volume depletion (e.g. patients receiving diuretics, particularly those with impaired renal function), treatment should be initiated under medical supervision and a lower starting dose should be considered.  The risk of adverse reactions, especially hypotension, hyperkalaemia and decreased renal function, may increase when Safebul® is used in combination with an ACE inhibitor. Triple combination of an ACE inhibitor, a mineralocorticoid receptor antagonist and Safebul® is also not recommended. The use of these combinations should be carried out under medical supervision and with close and frequent monitoring of renal function, electrolyte levels and blood pressure. ACE inhibitors  and angiotensin II receptor antagonists should not be used concomitantly in patients with diabetic nephropathy.  Hemodialysis. Renal artery stenosis. Kidney transplant. Hypotension. Anesthesia and surgery. Mitral valve and aortic stenosis. Primary hyperaldosteronism. Hyperkalemia, the concomitant use of Safebul® with potassium-saving diuretics, potassium supplements, salt substitutes containing potassium or other medicines that may increase potassium levels (e.g. heparin, co-trimoxazole also known as  trimethoprim/sulfamethoxazole) may increase serum potassium levels in hypertensive patients. Monitoring of potassium levels is recommended as required. Dual SRAA lock.    General warnings: In patients whose vascular tone and renal function depend mainly on RAAS activity (e.g. patients with severe congestive heart failure or underlying kidney disease, including renal artery stenosis), treatment with other medicines affecting this system has been associated with acute hypotension, uremia, oliguria or, rarely, acute renal failure. The possibility of similar effects with angiotensin II receptor antagonists cannot be excluded. The possibility of pregnancy in post-menarchy patients should be evaluated; appropriate information and/or actions should be provided to prevent the risk of exposure during pregnancy.  Warnings concerning excipients: this medicine contains lactose. Interactions: As with ACE inhibitors, concomitant use of ARAII and NAIDs could lead to an increased risk of worsening renal function, including a possible acute renal failure and an elevation of serum potassium,  especially in patients with a reduction in pre-existing kidney function. The combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and monitoring of renal function should be considered at the start of the concomitant therapy and periodically thereafter. Concomitant use of ARA II, including Safebul®, with other agents acting on RAAS (renin-angiotensin-aldosterone system) is associated with a higher incidence of hypotension, hyperkalemia, and changes in renal function compared to monotherapy. Pregnancy and lactation: due to the mechanism of action of angiotensin II antagonists, a risk to the fetus cannot be excluded. If pregnancy is detected during treatment, Safebul® should be discontinued as soon as possible. Safebul® is not recommended during lactation.   Most common side effects: respiratory infection, dizziness/vertigo, headache, hyperkalemia, hypotension. Coughing, headache, dizziness, rash, sinus arrhythmia, nasopharyngitis, pyrexia and oropharyngeal pain are very common in children.   CDS V05 Jun 2018.   The availability of presentations can vary between countries.   Safebul® 8 mg, 16 mg and 32 mg are available in Jamaica and Curacao.