No

Angiotensin II Antagonists

Alone or in combination with other antihypertensive agents in treating essential hypertension; may have an advantage over losartan due to minimal metabolism requirements and consequent use in mild to moderate hepatic impairment

C/D (2nd and 3rd trimesters)

Avoid use in the nursing mother, if possible, since candesartan may be excreted in breast milk. The drug 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.

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

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.

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

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

Dermatologic: Angioedema, rash (>0.5%)

Endocrine & metabolic: Hyperglycemia, hypertriglyceridemia

Gastrointestinal: Nausea, diarrhea, vomiting, dyspepsia, gastroenteritis

Genitourinary: Hyperuricemia, hematuria

Neuromuscular & skeletal: Back pain, arthralgia, paresthesias, increased CPK, myalgia, weakness

Respiratory: Upper respiratory tract infection, pharyngitis, rhinitis, bronchitis, cough, sinusitis, epistaxis, dyspnea

Miscellaneous: Diaphoresis (increased)

Signs and symptoms of overdose: Hypotension and tachycardia

Treatment is supportive

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

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.

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.

Onset of action: 2-3 hours

Peak effect: 6-8 hours

Duration: >24 hours

Distribution: V_d: 0.13 L/kg

Protein binding: 99%

Metabolism: Candesartan cilexetil is metabolized to candesartan by the intestinal wall cells

Bioavailability: 15%

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

Time to peak: 3-4 hours

Elimination: Total body clearance: 0.37 mL/kg/minute; renal clearance: 0.19 mL/kg/minute; 26% renal excretion

High concentrations occur in elderly compared to younger subjects; AUC may be doubled in patients with renal impairment

Adults: Oral: 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.

Food reduces the time to maximal concentration and increases the C_max

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

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.

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

None reported

No information available to require special precautions

No effects or complications reported

Take exactly as directed; do not miss doses, alter dosage, or discontinue without consulting prescriber. Do not alter salt or potassium intake without consulting prescriber. Change position slowly when rising from sitting or lying or when climbing stairs. May cause transient drowsiness, dizziness, or headache; avoid driving or engaging in tasks requiring alertness until response to drug is known. Small frequent meals may help reduce any nausea or vomiting. Report unusual weight gain or swelling of ankles and hands; persistent fatigue; unusual flu or cold symptoms or dry cough; difficulty breathing; chest pain or palpitations; swelling of eyes, face, or lips; skin rash; muscle pain or weakness; unusual bleeding (in urine, stool, or gums); or excessive sweating. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant - contraceptives may be recommended. Do not breast-feed.

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