Candesartan
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| Clinical data | |
|---|---|
| Pronunciation | /ˌkændɪˈsɑːrtən/ |
| Trade names | Atacand, others |
| Other names | Candesartan cilexetil |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a601033 |
| Pregnancy category |
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| Routes of administration | By mouth |
| ATC code | |
| Legal status | |
| Legal status | |
hepatic (CYP2C9) | |
| Elimination half-life | 9 hours |
| Excretion | Kidney 33%, faecal 67% |
| Identifiers | |
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Candesartan is an
It was patented in 1990 and approved for medical use in 1997.[2]
Medical uses
Hypertension
As with other angiotensin II receptor antagonists, candesartan is indicated for the treatment of
Heart failure
In heart failure patients, angiotensin receptor blockers such as candesartan and valsartan may be a suitable option for those who do not tolerate angiotensin-converting enzyme inhibitor medicines.[4][5] Randomised control trials have shown candesartan reduces heart failure hospitalisations and cardiovascular deaths for patients who have heart failure with reduced left ventricular ejection fraction (LVEF ≤ 40%).[5][6]
Prehypertension
In a four-year randomized controlled trial, candesartan was compared to placebo to see whether it could prevent or postpone the development of full-blown hypertension in people with so-called prehypertension. During the first two years of the trial, half of participants were given candesartan while the other half received placebo; candesartan reduced the risk of developing hypertension by nearly two-thirds during this period. In the last two years of the study, all participants were switched to placebo. By the end of the study, candesartan had significantly reduced the risk of hypertension, by more than 15%. Serious adverse effects were more common among participants receiving placebo than in those given candesartan.[7]
Prevention of atrial fibrillation
In 2005, meta-analysis results showed that angiotensin receptor blockers and angiotensin converting enzyme inhibitors considerably reduce the risk of atrial fibrillation in patients with coexisting heart failure and systolic left ventricular dysfunction.[8] Specifically, an analysis of the CHARM study showed benefits for Candesartan in reducing new occurrences of atrial fibrillation in patients with heart failure and reduced left ventricular function.[9] While these studies have demonstrated a potential additional benefit for candesartan when used in patients with systolic left ventricular dysfunction, additional studies are required to further elucidate the role of candesartan in the prevention of atrial fibrillation in other population groups.
Diabetic retinopathy
Use of antihypertensive drugs has been demonstrated to slow the progression of diabetic retinopathy; the role of candesartan specifically in reducing progression in type 1 and type 2 diabetes is still up for debate.[10][11][12] Results from a 2008 study on patients with type 1 diabetes showed there was no benefit in using candesartan to reduce progression of diabetic retinopathy when compared to placebo.[11] Candesartan has been demonstrated to reverse the severity (cause regression) of mild to moderate diabetic retinopathy in patients with type 2 diabetes.[12] The patient populations investigated in these studies were limited to mostly Caucasians and those younger than 75 years of age, so generalization of these findings to other population groups should be done with caution.[11][12]
Migraine prophylaxis
Candesartan may be helpful in migraine prevention as it has better tolerability and less side effects compared to other first line medications.[13][14] It has been recommended by multiple guidelines for migraine prophylaxis in adults with different levels of recommendations,[15][16][17][18][19] however further studies on larger populations are needed.
Adverse effects
As with other drugs that inhibit the renin–angiotensin system, if candesartan is taken by pregnant women during the second or third trimester, it can cause injury and in some cases, death of the developing fetus. Symptomatic hypotension may occur in people who take candesartan and are volume-depleted or salt-depleted, as can also occur when diuretics are coadministered. Reduction in renal glomerular filtration rate may occur; people with renal artery stenosis may be at higher risk. Hyperkalemia may occur; people who are also taking spironolactone or eplerenone may be at higher risk.[3]
Anemia may occur, due to inhibition of the renin–angiotensin system.[20]
As with other angiotensin receptor blockers, candesartan can rarely cause severe liver injury.[21]
Chemistry and pharmacokinetics
Candesartan is marketed as the
The use of a prodrug form increases the bioavailability of candesartan. Despite this, absolute bioavailability is relatively poor at 15% (candesartan cilexetil tablets) to 40% (candesartan cilexetil solution). Its IC50 is 15 μg/kg. Candesartan is not administered in its active form because the administration of the pro-drug would require greater doses and has an unfavorable adverse event profile.
Research
Candesartan is being investigated for its neuroprotective and anti-inflammatory properties. In an early Alzheimer's disease mouse model, candesartan significantly reduced amyloid burden and inflammation[22] and is being examined as a potential treatment for early Alzheimer's.[23] Rat models show that candesartan may have neuroprotective benefits that ameliorate certain central mechanisms of ageing and senescence.[24] Candesartan has also demonstrated some possible therapeutic anti-stress and anti-anxiety applications.[25] In a double-blind, placebo-controlled, randomized study, candesartan induced regression of left ventricular hypertrophy, and improved LV function and exercise tolerance with no side effects in patients with non obstructive hypertrophic cardiomyopathy.[26]
History
The compound known as TCV-116 (candesartan) was studied by Japanese scientists using standard laboratory rats. Animal studies were published showing the effectiveness of the compound in 1992–1993, with a pilot study on humans published in the summer of 1993.[27][28]
Names
The
References
- FDA. Retrieved 22 Oct 2023.
- ISBN 9783527607495.
- ^ a b "Candesartan label" (PDF). FDA. February 2016. For label updates see FDA index page for IND 020838
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- ^ "Therapeutic Guidelines | Therapeutic Guidelines". tgldcdp.tg.org.au. Retrieved 2023-05-12.
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- ^ "Guidelines". Canadian Headache Society. Retrieved 2023-05-12.
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- PMID 31811565.
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- PMID 19074594.
- PMID 1435062.
- PMID 8221818.
