Side Effects of Atacand (candesartan)

Atacand (candesartan) is an angiotensin receptor blocker (ARB) used to treat high blood pressure (hypertension). 

Angiotensin, formed in the blood by the action of angiotensin converting enzyme (ACE), is a powerful chemical that attaches to angiotensin receptors found in many tissues but primarily on smooth muscle cells surrounding blood vessels. 

Angiotensin's attachment to the receptors causes the muscle cells to contract and the blood vessels to narrow (vasoconstrict) which leads to an increase in blood pressure. Atacand blocks the angiotensin receptor and thereby prevents the action of angiotensin. As a result, blood vessels expand and blood pressure is reduced.

Common side effects of Atacand include

• headache,
• dizziness,
• fatigue,
• abdominal discomfort,
• diarrhea, and
• upper respiratory infections.

Serious side effects of Atacand include

• high blood potassium (hyperkalemia),
• impotence,
• reduced renal function,
• allergic reactions, and rarely,
• inflammation and destruction of muscle (rhabdomyolysis) and swelling of soft tissues including those of the throat and larynx (angioedema).

Drug interactions of Atacand include other medications that can increase the concentration of potassium in the blood, such as hydrodiuril, spironolactone, and potassium supplements, because it may lead to dangerous increases in potassium blood levels.

• Combining Atacand or other ARBs with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients who are elderly, fluid-depleted (including those on diuretic therapy), or with poor kidney function may result in reduced kidney function, including kidney failure. These effects usually are reversible.
• There have been reports that aspirin and other NSAIDs such as ibuprofen, indomethacin, and naproxen may reduce the effects of ARBs.
• An increase in lithium blood levels has been reported when lithium is combined with Atacand. Careful monitoring of lithium levels is recommended when Atacand and lithium are used concomitantly. 

When used in the second or third trimester of pregnancy, ARBs can cause injury and even death to the fetus. Atacand should not be used during pregnancy. When pregnancy is first detected, Atacand should be stopped. 

It is unknown if Atacand is secreted in human milk. Due to the possibility of harm to the nursing infant, if possible, Atacand should be discontinued by breastfeeding mothers.

The most common side effects of candesartan are:

• headache,
• dizziness,
• fatigue, abdominal discomfort,
• diarrhea, and
• upper respiratory infections.

Other important side effects include:

• hyperkalemia,
• impotence,
• reduced renal function, and
• allergic reactions.

Rhabdomyolysis (inflammation and destruction of muscle) and angioedema (swelling of soft tissues including those of the throat and larynx) are rare but serious side effects of candesartan.

Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Adult Hypertension

• Atacand has been evaluated for safety in more than 3600 patients/subjects, including more than 3200 patients treated for hypertension.
• About 600 of these patients were studied for at least 6 months and about 200 for at least 1 year.
• In general, treatment with Atacand was well tolerated. The overall incidence of adverse events reported with Atacand was similar to placebo.
• The rate of withdrawals due to adverse events in all trials in patients (7510 total) was 3.3% (i.e., 108 of 3260) of patients treated with Atacand as monotherapy and 3.5% (i.e., 39 of 1106) of patients treated with placebo.
•  In placebo-controlled trials, discontinuation of therapy due to clinical adverse events occurred in 2.4% (i.e., 57 of 2350) of patients treated with Atacand and 3.4% (i.e., 35 of 1027) of patients treated with placebo.
• The most common reasons for discontinuation of therapy with Atacand were headache (0.6%) and dizziness (0.3%).
• The adverse events that occurred in placebo-controlled clinical trials in at least 1% of patients treated with Atacand and at a higher incidence in candesartan cilexetil (n = 2350) than placebo (n = 1027) patients included
  • back pain (3% vs. 2%),
  • dizziness (4% vs. 3%),
  • upper respiratory tract infection (6% vs. 4%),
  • pharyngitis (2% vs. 1%), and
  • rhinitis (2% vs. 1%).

Pediatric Hypertension

• Among children in clinical studies, 1 in 93 children age 1 to < 6 and 3 in 240 age 6 to < 17 experienced worsening renal disease.
• The association between candesartan and exacerbation of the underlying condition could not be excluded.

Heart Failure

• The adverse event profile of Atacand in adult heart failure patients was consistent with the pharmacology of the drug and the health status of the patients.
• In the CHARM program, comparing Atacand in total daily doses up to 32 mg once daily (n=3803) with placebo (n=3796), 21.0% of patients discontinued Atacand for adverse events vs. 16.1% of placebo patients.

Postmarketing Experience

The following adverse reactions were identified during post-approval use of Atacand. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The following have been very rarely reported in post-marketing experience:

• Digestive: Abnormal hepatic function and hepatitis.
• Hematologic: Neutropenia, leukopenia, and agranulocytosis.
• Immunologic: Angioedema.
• Metabolic and Nutritional Disorders: Hyperkalemia, hyponatremia.
• Respiratory System Disorders: Cough.
• Skin and Appendages Disorders: Pruritus, rash and urticaria.

Rare reports of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers.

Agents Increasing Serum Potassium

• Co-administration of Atacand with potassium sparing diuretics, potassium supplements, potassium-containing salt substitutes or other drugs that raise serum potassium levels may result in hyperkalemia. Monitor serum potassium in such patients.

Lithium

• Increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists, including Atacand. Monitor serum lithium levels.

Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)

• In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including candesartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving candesartan and NSAID therapy.
• The antihypertensive effect of angiotensin II receptor antagonists, including candesartan may be attenuated by NSAIDs including selective COX-2 inhibitors.

Combination Blockade Of The Renin-Angiotensin System (RAS)

• Dual blockade of the RAS with angiotensin receptor blockers, ACE inhibitors, or aliskiren is associated with increased risks of hypotension, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
• Triple combination of Atacand with an ACE-inhibitor and a mineralocorticoid receptor antagonist is generally not recommended.
• Closely monitor blood pressure, renal function and electrolytes in patients on Atacand and other agents that affect the RAS.
• Do not co-administer aliskiren with Atacand in patients with diabetes.
• Avoid use of aliskiren with Atacand in patients with renal impairment (GFR <60 mL/min).