Safebul®HCT 8 mg/12.5 mg tablets. Each tablet contains 8 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. Safebul®HCT 16 mg/12.5 mg tablets. Each tablet contains 16 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. Safebul®HCT 32 mg/12.5 mg tablets. Each tablet contains 32 mg of candesartan cilexetil and 12.5 mg of hydrochlorothiazide. Safebul®HCT 32 mg/25 mg tablets. Each tablet contains 32 mg of candesartan cilexetil and 25 mg of hydrochlorothiazide. Excipients with known effect: lactose monohydrate. Therapeutic indications. Essential hypertension in adult patients with blood pressure that has not been completely controlled with Safebul® or hydrochlorothiazide monotherapy. Posology and administration method. The recommended dose is one table daily. A dose adjustment is recommended with the individual components (candesartan cilexetil and hydrochlorothiazide). A direct change from the monotherapy to Safebul®HCT can be considered when clinically adequate. The dose adjustment of Safebul® is recommended when the change is done from the monotherapy with hydrochlorothiazide. Safebul®HCT can be administered to patients with blood pressure that is not completely controlled with a monotherapy of Safebul® or hydrochlorothiazide or Safebul®HCT in lower doses. Most of the antihypertensive effect is reached generally within the 4 weeks of treatment initiation. A dose adjustment is not necessary for elderly patients. A dose adjustment of Safebul® is recommended in patients with risk of hypotension, as well as patients with possible volume depletion. A dose adjustment of Safebul® is recommended in patients with mild to moderate renal insufficiency, and mild to moderate hepatic insufficiency. The safety and efficacy in children from birth to 18 years of age has not been established. Contraindications. Hypersensitivity to active substances or any of the excipients or the active substances derived from sulfonamides. Pregnancy. Severe renal insufficiency. Severe hepatic insufficiency and/or colestasis. Refractory hypokalemia and hypercalcemia. Gout. Concomitant use of aliskiren in patients with diabetes mellitus or renal insufficiency. Warnings and precautions of use. In patients with renal insufficiency, periodic supervision is recommended to anticipate changes in the renal function in susceptible patients taking Safebul®HCT. There is no experience regarding its administration in patients with a recent renal transplant. Medicinal products that affect the renin-angiotensin-aldosterone system, like ARA-II, may increase the blood urea and the serum creatinine in patients with bilateral renal artery stenosis or artery stenosis from an only kidney. Symptomatic hypotension can occur in patients with sodium and/or intravascular volume depletion. The use of Safebul®HCT is not recommended until this condition has been corrected. Hypotension can occur during anesthesia and surgery on patients treated with ARAII due to the blockage of the renin-angiotensin system. Thiazides must be used with caution in patients with hepatic insufficiency or progressive liver disease. Caution is recommended in patients with hemodynamically significant stenosis of the aorta or mitral valve or with obstructive hypertrophic cardiomyopathy. It is not recommended in patients with primary hyperaldosteronism. Thiazides, including hydrochlorothiazides, can cause a hydroelectrolytic imbalance. Treatment with thiazidic diuretics can alter glucose tolerance. Increases in cholesterol and triglyceride levels have been associated with diuretic treatments with thiazides. Cases of photosensitivity reactions have been reported during the use of thiazidic diuretics. In patients with vascular tone and renal function dependent mainly on the renin-angiotensin-aldosterone system, treatment with medicines that affect this system, including ARAII, have been associated with acute hypotension, uremia, oliguria or, rarely, acute renal insufficiency. Hypersensitive reactions to hydrochlorothiazide may occur in patients with or without allergic or bronchial asthma antecedents, but are more likely in patients with these antecedents. Exacerbations or activation of systemic lupus erythematosus have been reported with the use of thiazidic diuretics. Based on two epidemiologic studies from the Danish National Cancer Registry, an increased non-melanoma skin cancer (NMSC) risk has been observed [basocelular carcinoma (BCC) and squamous cell carcinoma (SCC) with the exposure to increased cumulative doses of hydrochlorothiazide (HCTZ). The photosensitizing effects of HCTZ could act as a possible mechanism for NSCLC. Pregnancy. Due to the action mechanism of the angiotensin-II antagonists, the risk for the fetus cannot be excluded. Intrauterine exposure to ACE inhibitors during the second and third trimester has demonstrated lesions and death of the developing fetus. Furthermore, in retrospective data, the use of ACE inhibitors during the first trimester has been associated with a potential risk of birth defects. Cases of spontaneous abortion, oligohydramnios, and neonatal renal dysfunction have been notified when pregnant women have taken valsartan, an angiotensin-II antagonist inadvertently. Candesartan cilexetil must not be used during pregnancy. Hydrochlorothiazide can cross the placenta. Based on the pharmacological action mechanism of hydrochlorothiazide, its use during the second and third trimester can compromise the fetus-placenta perfusion and may cause fetal and neonatal effects like jaundice, electrolyte balance alterations, and thrombocytopenia. The use of Candesartan Cilexetil/Hydrochlorothiazide is not recommended during lactation. Adverse events. Respiratory infection. Dizziness/vertigo, headache. Hyperglycemia, hyperuricemia, electrolytic imbalance (including hyponatremia and hypokalemia). Weakness. Cholesterol and triglyceride increase. CDS Jan 2019.
The availability of presentations can vary between countries. Safebul®HCT 16 mg/12.5 mg tablets, Safebul®HCT 32 mg/12.5 mg and Safebul®HCT 32 mg/25 mg tablets are available in Jamaica and Curacao.