Home > Medical Reference > Complementary Medicine

Candesartan


Pronunciation

 (kan de SAR tan)


U.S. Brand Names

 Atacand®


Synonyms

 Candesartan Cilexetil


Generic Available

 No


Canadian Brand Names

 Atacand®


Use

 Alone or in combination with other antihypertensive agents in treating essential hypertension


Use - Unlabeled/Investigational

 Congestive heart failure


Pregnancy Risk Factor

 C/D (2nd and 3rd trimesters)


Pregnancy Implications

 Candesartan should be discontinued as soon as possible when pregnancy is detected. Drugs which act directly on renin-angiotensin can cause fetal and neonatal morbidity and death. Fetal and neonatal toxicity have been reported in infants born to women treated with candesartan during pregnancy.


Lactation

 Enters breast milk/contraindicated


Contraindications

 Hypersensitivity to candesartan or any component of the formulation; hypersensitivity to other A-II receptor antagonists; bilateral renal artery stenosis; pregnancy (2nd and 3rd trimesters)


Warnings/Precautions

 Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. Deterioration in renal function can occur with initiation. Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency; significant aortic/mitral stenosis.


Adverse Reactions

 May be associated with worsening of renal function in patients dependent on renin-angiotensin-aldosterone system.

Cardiovascular: Angina, MI, palpitation, tachycardia

Central nervous system: Dizziness, lightheadedness, drowsiness, headache, vertigo, anxiety, depression, somnolence, fever

Dermatologic: Angioedema, rash

Endocrine & metabolic: Hyperglycemia, hypertriglyceridemia, hyperuricemia

Gastrointestinal: Dyspepsia, gastroenteritis

Genitourinary: Hematuria

Neuromuscular & skeletal: Back pain, CPK increased, myalgia, paresthesia, weakness

Respiratory: Dyspnea, epistaxis, pharyngitis, rhinitis, upper respiratory tract infection

Miscellaneous: Diaphoresis (increased)

<1%, postmarketing, and/or case reports: Abnormal hepatic function, agranulocytosis, anemia, hepatitis, hyperkalemia, hyponatremia, leukopenia, neutropenia, pruritus, renal failure, renal impairment, rhinitis, sinusitis, thrombocytopenia, urticaria; rhabdomyolysis has been reported (rarely) with angiotensin-receptor antagonists


Overdosage/Toxicology

 Symptoms of overdose include hypotension and tachycardia. Treatment is supportive.


Drug Interactions

 Substrate of CYP2C8/9 (minor); Inhibits CYP2C8/9 (weak)

Lithium: Risk of toxicity may be increased by candesartan; monitor lithium levels.

NSAIDs: May decrease angiotensin II antagonist efficacy; effect has been seen with losartan, but may occur with other medications in this class; monitor blood pressure

Potassium-sparing diuretics (amiloride, spironolactone, triamterene): Increased risk of hyperkalemia.

Potassium supplements may increase the risk of hyperkalemia.

Trimethoprim (high dose) may increase the risk of hyperkalemia.


Ethanol/Nutrition/Herb Interactions

Food: Food reduces the time to maximal concentration and increases the Cmax.

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).


Mechanism of Action

 Candesartan is an angiotensin receptor antagonist. Angiotensin II acts as a vasoconstrictor. In addition to causing direct vasoconstriction, angiotensin II also stimulates the release of aldosterone. Once aldosterone is released, sodium as well as water are reabsorbed. The end result is an elevation in blood pressure. Candesartan binds to the AT1 angiotensin II receptor. This binding prevents angiotensin II from binding to the receptor thereby blocking the vasoconstriction and the aldosterone secreting effects of angiotensin II.


Pharmacodynamics/Kinetics

Onset of action: 2-3 hours

Peak effect: 6-8 hours

Duration: >24 hours

Distribution: Vd: 0.13 L/kg

Protein binding: 99%

Metabolism: To candesartan by the intestinal wall cells

Bioavailability: 15%

Half-life elimination (dose dependent): 5-9 hours

Time to peak: 3-4 hours

Excretion: Urine (26%)

Clearance: Total body: 0.37 mL/kg/minute; Renal: 0.19 mL/kg/minute


Dosage

 Adults: Oral:

Hypertension: Usual dose is 4-32 mg once daily; dosage must be individualized. Blood pressure response is dose-related over the range of 2-32 mg. The usual recommended starting dose of 16 mg once daily when it is used as monotherapy in patients who are not volume depleted. It can be administered once or twice daily with total daily doses ranging from 8-32 mg. Larger doses do not appear to have a greater effect and there is relatively little experience with such doses.

Congestive heat failure (unlabeled use): Target dose: 32 mg

Elderly: No initial dosage adjustment is necessary for elderly patients (although higher concentrations (Cmax) and AUC were observed in these populations), for patients with mildly impaired renal function, or for patients with mildly impaired hepatic function.

Dosage adjustment in hepatic impairment: No initial dosage adjustment required in mild hepatic impairment. Consider initiation at lower dosages in moderate hepatic impairment (AUC increased by 145%). No data available concerning dosing in severe hepatic impairment.


Monitoring Parameters

 Supine blood pressure, electrolytes, serum creatinine, BUN, urinalysis, symptomatic hypotension, and tachycardia


Patient Education

 Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed and do not discontinue without consulting prescriber. Preferable to take on an empty stomach, 1 hour before or 2 hours after meals. This drug does not eliminate need for diet or exercise regimen as recommended by prescriber. May cause dizziness, fainting, or lightheadedness (use caution when driving or engaging in tasks that require alertness until response to drug is known); postural hypotension (use caution when rising from lying or sitting position or climbing stairs); nausea or vomiting (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); or diarrhea (boiled milk, buttermilk, or yogurt may help). Report chest pain or palpitations; unusual weight gain or swelling of ankles and hands; persistent fatigue; unusual flu or cold symptoms or dry cough; respiratory difficulty; swelling of eyes, face, or lips; skin rash; muscle pain or weakness; unusual bleeding (blood in urine or stool, or from gums); or excessive sweating. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 2nd or 3rd trimester of pregnancy. Consult prescriber for appropriate contraceptive measures if necessary. Do not breast-feed.


Additional Information

 May have an advantage over losartan due to minimal metabolism requirements and consequent use in mild to moderate hepatic impairment


Anesthesia and Critical Care Concerns/Other Considerations

 The angiotensin II receptor antagonists appear to have similar indications as the ACE inhibitors. While these drugs have been shown to be effective in treating hypertension, their efficacy in heart failure is being vigorously evaluated. The angiotensin II antagonists are especially useful in providing an alternative therapy in those patients who have intractable cough in response to ACE inhibitor therapy. Similar to ACE inhibitors, pre-existing volume depletion caused by diuretic therapy may potentiate hypotension in response to angiotensin II antagonists. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. In the setting of heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema.


Cardiovascular Considerations

 The angiotensin II receptor antagonists appear to have similar indications as the ACE inhibitors. While these drugs have been shown to be effective in treating hypertension, their efficacy in heart failure is being vigorously evaluated. The angiotensin II antagonists are especially useful in providing an alternative therapy in those patients who have intractable cough in response to ACE inhibitor therapy. Similar to ACE inhibitors, pre-existing volume depletion caused by diuretic therapy may potentiate hypotension in response to angiotensin II antagonists. Concomitant NSAID therapy may attenuate blood pressure control; use of NSAIDs should be avoided or limited, with monitoring of blood pressure control. In the setting of heart failure, NSAID use may be associated with an increased risk for fluid accumulation and edema.

Because of the lack of effect on the response to bradykinin, angiotensin receptor blockers are less likely to be associated with nonrenin-angiotensin effects such as cough and angioedema. Because of a different site of action in comparison to ACE inhibitors, the angiotensin II antagonists do not cause increases in levels of bradykinin. These different sites of action have lead to the supposition that the ACE inhibitors and the angiotensin II antagonists may be used in combination for enhanced response. This possibility is currently being evaluated. The 2004 ACC/AHA STEMI guidelines suggest an angiotensin receptor blocker should be administered to STEMI patients who are intolerant of ACE inhibitors and who have either clinical or radiological signs of heart failure or LVEF <0.4.


Dental Health: Effects on Dental Treatment

 No significant effects or complications reported


Dental Health: Vasoconstrictor/Local Anesthetic Precautions

 No information available to require special precautions


Mental Health: Effects on Mental Status

 May cause dizziness or drowsiness; may rarely cause anxiety or depression


Mental Health: Effects on Psychiatric Treatment

 None reported


Dosage Forms

 Tablet, as cilexetil: 4 mg, 8 mg, 16 mg, 32 mg


References

Antman EM, Anbe SC, Alpert JS, et al, "ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction - Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction)," Circulation, 2004, 110:588-636. Available at: http://www.circulationaha.org/cgi/content/full/110/5/588. Last accessed October 26, 2004.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report," JAMA , 2003, 289(19):2560-71.

Conlin P, Moore T, Swartz S, et al, "Effect of Indomethacin on Blood Pressure Lowering by Captopril and Losartan in Hypertensive Patients," Hypertension , 2000, 36(3):461-5.

"Consensus Recommendations for the Management of Chronic Heart Failure. On Behalf of the Membership of the Advisory Council to Improve Outcomes Nationwide in Heart Failure," Am J Cardiol , 1999, 83(2A):1A-38A.

Hamroff G, Katz SD, Mancini D, et al, "Addition of Angiotensin II Receptor Blockade to Maximal Angiotensin-Converting Enzyme Inhibition Improves Exercise Capacity in Patients With Severe Congestive Heart Failure," Circulation , 1999, 99(8):990-2.

"K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, Classification, and Stratification. Kidney Disease Outcome Quality Initiative," Am J Kidney Dis , 2002, 39(2 Suppl 2):1-246. Available at: http://www.kidney.org/professionals/doqi/kdoqi/toc.htm. Accessed August 1, 2003.

McInnes GT, O'Kane KP, Jonker J, et al, "The Efficacy and Tolerability of Candesartan Cilexetil in an Elderly Hypertensive Population," J Hum Hypertens , 1997, 11(Suppl 2):75-80.

McKelvie RS, Yusuf S, Pericak D, et al, "Comparison of Candesartan, Enalapril, and Their Combination in Congestive Heart Failure : Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study: The RESOLVD Pilot Study Investigators," Circulation , 1999, 100(10):1056-64.

McMurray JJ, Ostergren J, Swedberg K, et al, "Effects of Candesartan in Patients With Chronic Heart Failure and Reduced Left-Ventricular Systolic Function Taking Angiotensin-Converting-Enzyme Inhibitors: The CHARM-Added Trial," Lancet , 2003, 362(9386):767-71.

Morsing P, Adler G, Brandt-Eliasson U, et al, "Mechanistic Differences of Various AT1-Receptor Blockers in Isolated Vessels of Different Origin," Hypertension , 1999, 33(6):1406-13.

Reif M, White WB, Fagan TC, et al, "Effects of Candesartan Cilexetil in Patients With Systemic Hypertension. Candesartan Cilexetil Study Investigators," Am J Cardiol , 1998, 82(8):961-5.

Riegger GA, Bouzo H, Petr P, et al, "Improvement in Exercise Tolerance and Symptoms of Congestive Heart Failure During Treatment With Candesartan Cilexetil," Circulation , 1999, 100(22):2224-30.

Swedberg K, Pfeffer M, Granger C, et al, "Candesartan in Heart Failure - Assessment of Reduction in Mortality and Morbidity (CHARM): Rationale and Design. Charm-Programme Investigators," J Card Fail , 1999, 5(3):276-82.

Yusuf S, Pfeffer MA, Swedberg K, et al, "Effects of Candesartan in Patients With Chronic Heart Failure and Preserved Left-Ventricular Ejection Fraction: The CHARM-Preserved Trial," Lancet , 2003, 362(9386):777-81.


International Brand Names

 Amias® (GB); Atacand® (AR, AT, AU, BE, CA, CH, CL, CO, CZ, DE, DK, ES, FI, FR, HU, IE, IL, MX, NL, NO, NZ, PL, PT, RO, RU, SE, SG, SI, TR, ZA); Atacand® Plus (SE); Blopress® (AT, BR, CH, CL, CO, CR, DE, GT, HN, ID, IT, JP, PA, PL, PT, SV, TH); Candesar® (IN); Kenzen® (FR); Parapres® (ES); Ratacand® (IT); Tiadyl® (AR)


A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is the first of its kind, requiring compliance with 53 standards of quality and accountability, verified by independent audit. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial process . A.D.A.M. is also a founding member of Hi-Ethics (www.hiethics.com) and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed medical professional should be consulted for diagnosis and treatment of any and all medical conditions. Call 911 for all medical emergencies. Links to other sites are provided for information only -- they do not constitute endorsements of those other sites. © 1997-2007 A.D.A.M., Inc. Any duplication or distribution of the information contained herein is strictly prohibited.
adam.com