Candesartan is an oral angiotensin II receptor blocker. It is available as a pro-drug, candesartan cilexetil, which undergoes hydrolysis in the gastrointestinal tract during absorption to its active form. Candesartan is marketed under a variety of brand names.
The FDA approved candesartan in June 1998 for the management of hypertension in adults. Clinical trials showed a once-daily 8 mg dose of candesartan to be as effective as a 50 mg dose of losartan, another angiotensin II receptor blocker, or a 10 to 20 mg dose of enalapril, an ACE inhibitor, in lowering blood pressure. The FDA also approved the use of candesartan to treat hypertension in adolescents and children aged one and older in October of 2009.,
In February of 2005, the FDA approved the use of candesartan in adults with heart failure in New York Heart Association classes 2 to 4. The placebo-controlled CHARM studies have shown the efficacy of candesartan in these specific subpopulations:
The CHARM studies demonstrated a reduction in cardiovascular mortality and hospitalizations due to congestive heart failure, with either candesartan monotherapy or in combination with an ACE inhibitor.
Candesartan is often prescribed as monotherapy for the management of hypertension and heart failure. However, a combination formulation exists with low-dose hydrochlorothiazide, a thiazide diuretic. This combination helps to achieve an additional antihypertensive effect.
Candesartan, like ACE inhibitors such as enalapril and direct renin inhibitors such as aliskiren, interferes with the renin-angiotensin-aldosterone system (RAAS). Normally, renin is released by renal juxtaglomerular cells in response to decreased renal perfusion pressure, increased sympathetic tone, and decreased delivery of sodium chloride to macula densa cells in the distal convoluted tubule of the nephron. Angiotensinogen, released by the liver, is cleaved into angiotensin I by renin. Angiotensin I is converted into angiotensin II in the lungs by the action of angiotensin-converting enzyme (ACE). Angiotensin II has several effects, including:
Candesartan works by antagonizing the angiotensin II receptor type 1. This activity blocks the effects mentioned above of angiotensin II and leads to a reduction in blood pressure and fluid retention. Since candesartan only blocks the binding of angiotensin II to its target receptor, its action is independent of the upstream steps leading to angiotensin II biosynthesis. An angiotensin II receptor type 2 also exists, but it plays no role in the maintenance of blood pressure and normal hemodynamics. Furthermore, candesartan binds angiotensin II receptor type 1 ten-thousand times more strongly than it does type 2.
Candesartan is administered orally and is available as 4 mg, 8 mg, 16 mg, and 32 mg tablets. For patients who have difficulty swallowing, oral suspensions are available.
Heart failure: Adults should receive 4 to 8 mg once daily.
Migraine prophylaxis: Adults should receive 16 mg once daily.
The most common adverse effects reported for candesartan are symptomatic hypotension, abnormal renal function, and hyperkalemia. In the CHARM program, symptomatic hypotension, impaired renal function (rise in creatinine), and hyperkalemia occurred with an incidence of 18.8%, 12.5%, and 6.3%, respectively. Hypotension is most common in patients who are volume- or salt-depleted secondary to dietary restriction, dialysis, diarrhea, emesis, or diuretic use.
Other reported side effects include headache, back pain, angioedema, and upper respiratory tract infections, but these are very rare clinically.
Candesartan is considered a teratogen and has a black box warning for fetal toxicity. If used in the second or third trimesters of pregnancy, medications that interfere with the renin-angiotensin-aldosterone system diminish fetal renal function. There is an increased risk of morbidity and death secondary to oligohydramnios results from decreased renal function. These neonates may develop skull hypoplasia, lung hypoplasia, hypotension, renal failure, and may ultimately expire.
The only major contraindication to candesartan is hypersensitivity to the medication or any of its components.
Patients taking candesartan should have their blood pressure routinely measured to assess for adequate blood pressure response to the medication. Additionally, clinicians should monitor patients for adverse effects of symptomatic hypotension, including dizziness, lightheadedness, nausea, syncope, and fatigue.
Hyperkalemia and impaired renal function can occur with candesartan use. Therefore, serum potassium and renal function should receive periodic monitoring.
Candesartan overdose would most likely manifest as symptomatic hypotension, dizziness, and reflexive tachycardia. Patients who develop symptomatic hypotension should have their vital signs monitored. Patients should receive instruction to lie down supine and raise their legs. If this is insufficient, clinicians can initiate fluid resuscitation and/or supportive pharmacotherapy to increase blood pressure.
Candesartan is an antihypertensive agent that clinicians also use to manage congestive heart failure. The drug is effective, but prescribers need to be aware of its side effects. The entire interprofessional team, including clinicians, nurses, and pharmacists, can collaborate to make treatment with candesartan more effective while minimizing adverse effects, thereby achieving optimal patient outcomes.
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