Candesartan Cilexetil

Trade Names:Atacand- Tablets 4 mg- Tablets 8 mg- Tablets 16 mg- Tablets 32 mg

Pharmacology

Antagonizes the angiotensin ΙΙ effect (vasoconstriction and aldosterone secretion) by blocking the angiotensin ΙΙ receptor (AT ₁ receptor) in vascular smooth muscle and the adrenal gland, producing decreased BP.

Pharmacokinetics

Absorption

Bioavailability is about 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 t _½ is about 9 h. Plasma Cl is 0.37 mL/min/kg. Renal Cl is 0.19 mL/min/kg. About 26% is excreted unchanged in urine.

Special Populations

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

The AUC and C _max increased 30% and 56% in mild impairment and 145% and 73% in moderate impairment, respectively.

C _max is about 50% higher; AUC is about 80% higher.

Indications and Usage

Treatment of hypertension; treatment of heart failure.

Contraindications

Standard considerations.

Dosage and Administration

PO Initial dose: 16 mg/day; consider lower dose if volume-depleted. Total daily doses range from 8 to 32 mg in 1 or 2 doses.

PO Initial dose: 4 mg/day. Double the dose at 2wk intervals to achieve target dose of 32 mg/day.

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

General Advice

Administer without regard to food. Administer with food if GI upset occurs.

Storage/Stability

Store at controlled room temperature (59° to 86°F) in a tightly closed container.

Drug Interactions

Plasma concentrations of lithium may be increased, resulting in an increase in pharmacologic and adverse reactions.

Coadministration may cause elevated serum potassium concentrations in certain high-risk patients.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Dizziness (4%); fatigue, headache (1%).

Dermatologic

Pruritis, urticaria (postmarketing).

EENT

Pharyngitis, rhinitis (2%); sinusitis.

GI

Abdominal pain, diarrhea, nausea, vomiting (1%).

Genitourinary

Renal failure, renal function impairment (postmarketing).

Hematologic

Agranulocytosis, leukopenia, neutropenia (postmarketing).

Hepatic

Hepatic function impairment, hepatitis (postmarketing).

Metabolic

Hyperkalemia, hyponatremia (postmarketing).

Respiratory

Upper respiratory tract infection (6%); bronchitis (1%); cough.

Miscellaneous

Back pain (3%); arthralgia, chest pain, peripheral edema (1%); albuminuria; edema.

Precautions

Pregnancy

Category D (second and third trimester); Category C (first trimester).

Lactation

Undetermined.

Children

Safety and efficacy not established.

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 CHF).

Heart failure

Use with caution when initiating therapy; hypotension may occur.

Hyperkalemia

May occur, especially in heart failure patients.

Hypotension/Volume-depleted patients

Symptomatic hypotension may occur in patients who are intravascularly volume depleted (eg, those treated with diuretics). Correct these conditions prior to administration or use a lower starting dose.

Overdosage

Symptoms

Bradycardia, dizziness, hypotension, tachycardia.

Patient Information

• Provide patient information leaflet.
• Instruct patient to take the medication as prescribed at the same time each day.
• Inform patient that candesartan can control but does not cure hypertension.
• Caution patient to take the dose exactly as prescribed and not to stop taking the medication even if feeling better.
• Instruct patient not to decrease or increase the dosage without talking with health care provider.
• Inform patient of the following possible adverse reactions: dry cough, renal function impairment, fetal injury.
• Advise women to notify health care provider if pregnant, planning to become pregnant, or breast-feeding. Advise women to discontinue candesartan as soon as possible if pregnancy is detected.
• Instruct the patient in BP and pulse measurement skills. Caution patient to call health care provider if abnormal readings occurs.
• Instruct patient on methods of fall prevention, including rising slowly and sitting on the side of the bed before standing, especially early in therapy.
• Instruct patient that other medications, especially hypertensive medications, can have additive or synergistic effects. Have patient inform health care provider of all medication being taken, including OTC drugs.
• Inform patient of the importance of adjunctive therapies, such as dietary planning, a regular exercise program, weight reduction, a low sodium diet, smoking cessation program, alcohol reduction, and stress management.
• Instruct patient to monitor renal, hepatic, and hematologic symptoms including urinary output and any discomfort during urination, weakness, fatigue, dizziness, lightheadedness, and jaundice. Patient should inform primary caregiver if symptoms occur.
• Warn patient that inadequate fluid intake, excessive perspiration, diarrhea, or vomiting, resulting in reduced fluid volume, may lead to an excessive fall in BP, lightheadedness, and possible fainting.
• Tell patient not to use potassium supplement or salt substitutes containing potassium to prevent possible hyperkalemia.
• Instruct patient to report any indications of an infection such as a sore throat, which could indicate neutropenia.
• Caution patient to inform health care provider or dentist of drug therapy prior to surgery or treatment.

Copyright © 2009 Wolters Kluwer Health.