What are the side effects of Candesartan (Angiotensin II receptor antagonist)?

Candesartan Side Effects

Candesartan causes hypotension, hyperkalemia, and worsening renal function as its primary side effects, all resulting from suppression of the renin-angiotensin system, with these risks being similar to ACE inhibitors but with a significantly lower incidence of cough. 1

Primary Side Effects Related to Renin-Angiotensin System Blockade

Hypotension is the most clinically significant side effect, particularly in volume-depleted patients:

• Symptomatic hypotension occurs most commonly in patients with prolonged diuretic therapy, dietary salt restriction, dialysis, diarrhea, or vomiting 2
• In heart failure patients, candesartan may cause excessive hypotension leading to oliguria, azotemia, and rarely acute renal failure and death 1
• Patients require close monitoring for the first 2 weeks of treatment and after any dose increases 1
• Correct volume and salt depletion before initiating therapy 2

Hyperkalemia develops through decreased aldosterone production and reduced potassium excretion:

• In the CHARM trials, hyperkalemia led to drug discontinuation with an odds ratio of 2.7-2.8 compared to placebo 1
• Risk is substantially higher in patients with chronic kidney disease, heart failure, or diabetes mellitus 1, 3
• Monitor serum potassium within 1-2 weeks after initiation or dose changes 1, 3
• Avoid concurrent use with potassium supplements, potassium-sparing diuretics, or salt substitutes containing potassium 2

Renal dysfunction can occur, particularly in patients whose renal function depends on the renin-angiotensin system:

• Highest risk in patients with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion 2
• Monitor renal function periodically; consider withholding therapy if clinically significant decline occurs 2
• Changes in renal function including acute renal failure can develop 2

Angioedema Risk

Angioedema is much less frequent with candesartan than with ACE inhibitors, but cross-reactivity can occur:

• Some patients who developed angioedema to ACE inhibitors later developed angioedema to ARBs including candesartan 1
• While rare, this represents a serious adverse effect requiring immediate discontinuation 1

Common Mild Side Effects

The most frequently reported adverse events are generally mild to moderate:

• Headache, upper respiratory tract infection, back pain, and dizziness are most common 4
• The incidence of these effects is similar to placebo 4, 5
• Cough occurs at a rate similar to placebo, making candesartan an excellent alternative for patients intolerant of ACE inhibitors due to cough 1, 4, 5
• Adverse events are not dose-related and tolerability does not differ with age or gender 4

Metabolic and Laboratory Abnormalities

Electrolyte disturbances beyond hyperkalemia:

• When combined with hydrochlorothiazide, hypokalemia can occur (2.5% incidence) 2
• Hyperkalemia occurred in 0.4% of patients in clinical trials versus 1.0% with placebo 2
• No patients were discontinued due to potassium abnormalities at doses of 16-32 mg daily 2

Pregnancy and Fetal Toxicity

Candesartan is absolutely contraindicated in pregnancy:

• Use during second and third trimesters causes fetal renal dysfunction, oligohydramnios, fetal lung hypoplasia, skeletal deformations, skull hypoplasia, anuria, hypotension, renal failure, and death 2
• Discontinue immediately when pregnancy is detected 2
• Infants with in utero exposure require close observation for hypotension, oliguria, and hyperkalemia 2

Drug Interaction-Related Side Effects

Dual blockade of the renin-angiotensin system significantly increases adverse effects:

• Combining candesartan with ACE inhibitors increases risks of hypotension, hyperkalemia, and renal dysfunction without improving outcomes 1
• The combination of candesartan with both ACE inhibitors and aldosterone antagonists further increases risks and cannot be recommended 1
• Do not co-administer with aliskiren in diabetic patients 2

NSAIDs (including COX-2 inhibitors) can worsen side effects:

• May cause deterioration of renal function, including acute renal failure, particularly in elderly or volume-depleted patients 2
• Can attenuate the antihypertensive effect of candesartan 2
• Monitor renal function periodically with concurrent NSAID use 2

Lithium toxicity risk:

• Increases in serum lithium concentrations and lithium toxicity have been reported 2
• Monitor serum lithium levels during concomitant use 2

Special Populations Requiring Enhanced Monitoring

Patients at particular risk for adverse effects include those with:

• Systolic blood pressure below 80 mmHg 1
• Low serum sodium 1
• Diabetes mellitus 1
• Impaired renal function (GFR <60 mL/min) 3
• Heart failure 1

These patients merit particularly close surveillance during therapy, with blood pressure (including postural changes), renal function, and potassium reassessed within 1-2 weeks after initiation and after dose changes 1.