Pronunciation:

(kan de SAR tan & hye droe klor oh THYE a zide)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Pregnancy Implications:

Candesartan: C/D (2nd and 3rd trimesters): Discontinue as soon as possible when pregnancy is detected. Drugs that act directly on renin-angiotensin can cause fetal and neonatal morbidity and death. Adverse effects to the fetus appear to be limited to the 2nd and 3rd trimesters.

Hydrochlorothiazide: B (per manufacturer), D (based on expert analysis): Although there are no adequate and well-controlled studies using hydrochlorothiazide in pregnancy, thiazide diuretics may cause an increased risk of congenital defects. Hypoglycemia, hypokalemia, hyponatremia, jaundice, and thrombocytopenia are also reported as possible complications to the fetus or newborn.

Lactation:

Contraindications:

Warnings/Precautions:

Candesartan: Deterioration in renal function can occur with initiation. Use caution in patients with CHF. Use with caution in unilateral renal artery stenosis and pre-existing renal insufficiency; significant aortic/mitral stenosis.

Hydrochlorothiazide: Hepatic coma can be caused by electrolyte disturbances in patients with severe hepatic dysfunction. Can cause SLE exacerbation or activation. Hypersensitivity reactions can occur and may be more likely in patients with bronchial asthma. Gout can be precipitated in certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure. Electrolyte disturbances (hypokalemia, hypochloremic alkalosis, hypomagnesemia, hypercalcemia, hyponatremia) can occur. Cautious use in diabetics; may see a change in glucose control. Avoid in severe renal disease (ineffective); may precipitate azotemia; discontinue or consider withholding if renal impairment occurs. Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported with thiazides. Photosensitization may occur.

Adverse Reactions:

1% to 10%:

Central nervous system: Dizziness (3%), headache (3%, placebo 5%)

Neuromuscular & skeletal: Back pain (3%)

Respiratory: Upper respiratory tract infection (4%)

Miscellaneous: Flu-like symptoms (2%)

<1%: Abdominal pain, abnormal ECG, abnormal hepatic function, agranulocytosis, angina pectoris, angioedema (<0.5%), anxiety, arthralgia, arthritis, arthrosis, asthenia, bradycardia, bronchitis, BUN increased, chest pain, conjunctivitis, cough, CPK increased, cystitis, depression, dermatitis, diaphoresis increased, diarrhea, dyspepsia, dyspnea, eczema, epistaxis, extrasystoles, fatigue, gastritis, gastroenteritis, hematuria, hepatitis, hypesthesia, hyperglycemia, hyperuricemia, hypokalemia, infection, insomnia, leg cramps, leukopenia, myalgia, MI (<0.5%), nausea, neutropenia, pain, palpitation, paresthesia, peripheral edema, pharyngitis, pruritus, rash, rhinitis, sciatica, sinusitis, tachycardia, tinnitus, transaminases increased, urinary tract infection, urticaria, vertigo, viral infection, vomiting; rhabdomyolysis has been reported (rarely) with angiotensin-receptor antagonists

Overdosage/Toxicology:

Candesartan: Information is limited; expected symptoms would be dizziness, hypotension, tachycardia. Bradycardia may also occur. Treatment is supportive. Not removed by hemodialysis.

Hydrochlorothiazide: Hypochloremia, hypokalemia, hyponatremia, and dehydration may occur. Treatment is supportive.

Drug Interactions:

Also see individual agents.

Ethanol/Nutrition/Herb Interactions:

Stability:

Mechanism of Action:

Candesartan: 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.

Hydrochlorothiazide: Inhibits sodium reabsorption in the distal tubules causing increased excretion of sodium and water as well as potassium and hydrogen ions

Pharmacodynamics/Kinetics:

Dosage:

Usual dosage range:

Candesartan: 8-32 mg/day, given once daily or twice daily in divided doses

Hydrochlorothiazide: 12.5-50 mg once daily

Dosage adjustment in renal impairment: Serum levels of candesartan are increased and the half-life of hydrochlorothiazide is prolonged in patients with renal impairment. Do not use if Clcr<30 mL/minute

Dosage adjustment in hepatic impairment: Use with caution

Elderly: No initial dosage adjustment is recommended in patients with normal renal and hepatic function; some patients may have increased sensitivity

Monitoring Parameters:

Dietary Considerations:

Patient Education:

Nursing Implications:

Cardiovascular Considerations:

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Dosage Forms:

16-12.5: Candesartan 16 mg and hydrochlorothiazide 12.5 mg

32-12.5: Candesartan 32 mg and hydrochlorothiazide 12.5 mg

International Brand Names: