High Cholesterol? Learn about treatments

Candesartan Cilexetil

Pronunciation

Pronunciation: KAN-de-SAR-tan sye-LEX-e-til
Class: Angiotensin II receptor antagonist

Trade Names

Atacand
- Tablets, oral 4 mg
- Tablets, oral 8 mg
- Tablets, oral 16 mg
- Tablets, oral 32 mg

Pharmacology

Antagonizes the angiotensin II effect (vasoconstriction and aldosterone secretion) by blocking the angiotensin II receptor (AT2 receptor) in vascular smooth muscle and the adrenal gland, producing decreased BP.

Slideshow: Living with Your Migraines: Tips for Treatment and Prevention

Pharmacokinetics

Absorption

Bioavailability is approximately 15%. T max is 3 to 4 h.

Distribution

Vd is 0.13 L/kg. More than 99% protein bound.

Metabolism

Candesartan cilexetil is bioactivated by ester hydrolysis during absorption from the GI tract to candesartan. Candesartan undergoes minor hepatic metabolism by O-deethylation to an inactive metabolite.

Elimination

The half-life is approximately 9 h. Plasma Cl is 0.37 mL/min/kg. Renal Cl is 0.19 mL/min/kg. Approximately 26% is excreted unchanged in the urine.

Special Populations

Renal Function Impairment

In hypertensive patients with CrCl less than 30 mL/min/1.73 m 2 , the AUC and C max are approximately doubled. In heart failure patients with renal impairment, AUC is 36% and 65% higher and C max is 15% and 55% higher in patients with mild and moderate renal impairment, respectively.

Hepatic Function Impairment

The AUC and C max increased 30% and 56% in mild impairment and 145% and 73% in moderate impairment, respectively. The pharmacokinetics after candesartan administration have not been investigated in patients with severe hepatic impairment.

Elderly

C max is approximately 50% higher; AUC is approximately 80% higher.

Children

Exposure is similar to adults.

Gender

There is no difference in the pharmacokinetics of candesartan between men and women.

Heart failure

The pharmacokinetics in heart failure patients are similar to those in healthy elderly volunteers.

Indications and Usage

Treatment of hypertension; treatment of heart failure.

Unlabeled Uses

Prevention of migraine in adults.

Contraindications

Hypersensitivity to any component of this product.

Dosage and Administration

Heart Failure
Adults

PO 4 mg/day initially. Double the dose at 2-wk intervals to achieve a target dosage of 32 mg/day.

Hypertension
Adults

PO 16 mg/day initially when used as monotherapy in patients who are not volume depleted. Total daily doses range from 8 to 32 mg in 1 or 2 doses.

Children 6 to 16 y of age

PO Initially, 8 to 16 mg/day initially for children weighing more than 50 kg and 4 to 8 mg/day for children weighing less than 50 kg. Usual dosages range from 4 to 32 mg/day for children weighing more than 50 kg and 2 to 16 mg/day for children weighing less than 50 kg.

Children 1 to 5 y of age

0.2 mg/kg initially. Usual dosages range from 0.05 to 0.4 mg/kg/day.

Hepatic Function Impairment

Consider using a lower initial dose in patients with moderate hepatic impairment.

Renal Function Impairment

Do not administer to pediatric patients with a glomerular filtration rate less than 30 mL/min/1.73 m 2 .

Volume-Depleted Patients

For patients with possible depletion of intravascular volume (eg, patients treated with diuretics, particularly those with impaired renal function), consider administering a lower dose.

General Advice

  • Administer without regard to food.
  • Administer either once daily or divided into 2 equal doses.
  • Candesartan oral suspension can be prepared in concentrations within the range of 0.1 to 2 mg/mL. Typically, a concentration of 1 mg/mL will be suitable for the prescribed dose. Any strength of candesartan tablets can be used in the preparation of the suspension. Refer to the manufacturer's prescribing information for preparing the oral suspension.
  • Shake the suspension well before each use.

Storage/Stability

Store between 59° and 86°F. Store the oral suspension at room temperature (below 86°F) and use within 30 days after first opening. Do not freeze.

Drug Interactions

ACE inhibitors (eg, captopril)

Dual blockade with ACE inhibitors and candesartan may result in additive renal toxicity and hyperkalemia. If monotherapy is not feasible, coadminister with caution and closely monitor renal function.

Diuretics

In patients with possible intravascular volume and/or salt depletion (eg, patients treated with diuretics), symptomatic hypotension may occur. Correct these conditions prior to candesartan administration, or start treatment under close monitoring and consider administration of a lower dose of candesartan.

Lithium

Plasma concentrations of lithium may be increased, resulting in an increase in pharmacologic effects and adverse reactions. Closely monitor lithium concentrations and adjust the dose as needed.

NSAIDs (eg, celecoxib, ibuprofen)

The antihypertensive effect of candesartan may be decreased. In addition, coadministration of NSAIDs with candesartan in patients who are elderly, volume depleted (including those on diuretics), or renal function impaired may result in deterioration of renal function. Monitor BP and renal function.

Potassium preparations

Candesartan may decrease the renal excretion of potassium, increasing the risk of hyperkalemia and possibly resulting in cardiac arrhythmias or cardiac arrest. Closely monitor serum potassium. Adjust the potassium preparation dose as needed.

Potassium-sparing diuretics (eg, amiloride, spironolactone, triamterene)

Coadministration may cause elevated serum potassium concentrations in certain high-risk patients. Monitor serum potassium, especially in patients with heart failure, during dose escalation and periodically thereafter.

Trimethoprim

The risk of hyperkalemia may be increased because of additive inhibition or potassium renal excretion. If coadministration cannot be avoided, closely monitor potassium concentrations and the clinical response. Adjust the candesartan dose as needed.

Adverse Reactions

Cardiovascular

Hypotension (19%); palpitation, tachycardia (1% or more); angina pectoris; MI.

CNS

Dizziness (4%); fatigue, headache (more than 1%); anxiety, asthenia, depression, paresthesia, somnolence, vertigo (1% or more).

Dermatologic

Rash, sweating increased (1% or more); pruritus, urticaria (postmarketing).

EENT

Pharyngitis, rhinitis (2%); sinusitis (more than 1%).

GI

Abdominal pain, diarrhea, nausea, vomiting (more than 1%); dyspepsia, gastroenteritis (1% or more).

Genitourinary

Increased serum creatinine (13%); albuminuria (more than 1%); hematuria (1% or more); increased BUN; renal failure, renal impairment (postmarketing).

Hematologic

Decreased Hct (2%); decreased Hgb; thrombocytopenia; agranulocytosis, leukopenia, neutropenia (postmarketing).

Hepatic

Elevated liver enzymes, elevated serum bilirubin; hepatic impairment, hepatitis (postmarketing).

Metabolic

Hyperkalemia (6%); creatine phosphokinase increased, hyperglycemia, hypertriglyceridemia, hyperuricemia (1%); hyponatremia (postmarketing).

Musculoskeletal

Back pain (3%); arthralgia (more than 1%); myalgia (1% or more); rhabdomyolysis (postmarketing).

Respiratory

Upper respiratory tract infection (6%); bronchitis, cough (more than 1%); dyspnea, epistaxis (1% or more).

Miscellaneous

Chest pain, peripheral edema (more than 1%); fever (1% or more); angioedema.

Precautions

Warnings

Pregnancy

When used in pregnancy during the second and third trimesters, drugs that act directly on the renin-angiotensin system can cause injury and even death to the developing fetus. When pregnancy is detected, discontinue therapy as soon as possible.


Monitor

Monitor BP, serum potassium, volume status, and renal function during initiation of therapy, dosage escalation, and periodically thereafter.


Pregnancy

Category C (first trimester); Category D (second and third trimesters). Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidity and death when administered to pregnant women.

Lactation

Undetermined.

Children

Children younger than 1 y must not receive candesartan for hypertension.

Renal Function

Use caution in treating patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe heart failure). Treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria or progressive azotemia and (rarely) with acute renal failure and/or death.

Hyperkalemia

May occur, especially in heart failure patients.

Hypotension

In patients with an activated renin-angiotensin system, such as volume- and/or salt-depleted patients (eg, those being treated with diuretics), symptomatic hypotension may occur. Patients with heart failure given candesartan commonly have some reduction in BP. In patients with symptomatic hypotension, this may require temporarily reducing the dose of candesartan, the diuretic, or both, and volume repletion. Correct these conditions prior to administration of candesartan or start the treatment under close medical supervision.

Renal effects

In heart failure patients, increases in serum creatinine may occur. Dosage reduction, discontinuation of the diuretic or candesartan, and volume repletion may be required.

Overdosage

Symptoms

Bradycardia, dizziness, hypotension, tachycardia.

Patient Information

  • Inform women of childbearing age about the consequences of second- and third-trimester exposure to drugs that act on the renin-angiotensin system and that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. Ask these patients to report pregnancies to their doctors as soon as possible. Question adolescents on a regular basis as to changes in menstrual pattern and the possibility of pregnancy.
  • Advise patients to take candesartan with or without food.
  • If BP is not controlled with this medicine alone, inform patients that diuretics or other BP medicines may be prescribed.
  • Inform patients that lifestyle changes (eg, stopping smoking, losing weight, exercising, limiting salt in diet) also help to lower BP.

Copyright © 2009 Wolters Kluwer Health.

Hide
(web1)