Overview
11 DESCRIPTION Candesartan cilexetil, a prodrug, is hydrolyzed to candesartan during absorption from the gastrointestinal tract. Candesartan is a selective AT 1 subtype angiotensin II receptor antagonist. Candesartan cilexetil, a nonpeptide, is chemically described as (±) - 1 - Hydroxyethyl 2 - ethoxy - 1 - [ p - ( o - 1 H - tetrazol - 5 ylphenyl) benzyl] - 7 -benzimidazolecarboxylate,...
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT 1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is, therefore, independent of the pathways for angiotensin II synthesis.
Indications
- 1 INDICATIONS AND USAGE Candesartan cilexetil tablets are an angiotensin II receptor blocker (ARB) indicated for: · Treatment of hypertension in adults and children 1 to
Common Doses
- 16 mg
- 32 mg
- 0.2 mg
- 0.4 mg
Dosage
2 DOSAGE AND ADMINISTRATION Starting Dose Target Dose Adult Hypertension (2.1) 16 mg tablet once daily 8 to 32 mg tablet total daily dose Pediatric Hypertension (1 to ˂6 years) (2.2) 0.2 mg/kg oral suspension once daily 0.05 to 0.4 mg/kg oral suspension once daily or consider divided dose Pediatric Hypertension (6 to ˂17 years) (2.2) 50 kg 8 to 16 mg tablet once daily 50 kg 4 to 32 mg tablet once daily or consider divided dose Adult Heart Failure (2.
Black Box Warning
WARNING: FETAL TOXICITY • When pregnancy is detected, discontinue candesartan cilexetil tablets as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. WARNING: FETAL TOXICITY See full prescribing information for complete boxed warning. • When pregnancy is detected, discontinue candesartan cilexetil tablets as soon as possible. (5.1, 8.
Contraindications
- 4 CONTRAINDICATIONS Candesartan cilexetil tablets are contraindicated in patients who are hypersensitive to candesartan. Do not co-administer aliskiren with candesartan cilexetil tablets in patients with diabetes [see Drug Interactions (7.4)]. Known hypersensitivity to product components (4). Do not co-administer aliskiren with candesartan cilexetil tablets in patients with diabetes (4).
Side Effects
- 6 ADVERSE REACTIONS · Most common adverse reactions which caused adult patients to discontinue therapy for: o Hypertension were headache (0.6%) and dizziness (0.3%) (6.1). o Heart Failure were hypotension (4.1%) (5.3), abnormal renal function (6.3%) (5.4), and hyperkalemia (2.4%) (5.5). To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS · Lithium: Increases in serum lithium concentrations and toxicity (7). · NSAIDs use may lead to increased risk of renal impairment and loss of antihypertensive effect (7). · Dual inhibition of the renin- angiotension system: Increased risk of renal impairment, hypotension, and hyperkalemia (7) . • Combined inhibition of the renin-angiotensin system: Increased risk of renal impairment, hypotension, and hyperkalemia (7). 7.