candesartan (Rx)

Frequency Not Defined

Peripheral edema

Dizziness

Hypertriglyceridemia

Hyperuricemia

Fatigue

Abdominal pain

Diarrhea

Nausea

Arthralgia

Back pain

Chest pain

Angina

Tachycardia

MI

Palpitation

Albuminuria

Bronchitis

Coughing

Pharyngitis

Dyspepsia

Gastroenteritis

Rhinitis

URI

Rash

Angioedema

Postmarketing Reports

Digestive: Abnormal hepatic function and hepatitis

Hematologic: Neutropenia, leukopenia, and agranulocytosis

Immunologic: Angioedema

Metabolic and nutritional disorders: Hyperkalemia, hyponatremia

Respiratory system disorders: Cough

Skin and appendages disorders: Pruritus, rash and urticaria

Rare reports of rhabdomyolysis have been reported with ARBs

Contraindications

Hypersensitivity

Severe hepatic impairment

Do not coadminister with aliskiren in patients with diabetes

Cautions

History of angioedema

Hypovolemia

Risk of hypotension, especially in hypovolemic/hyponatremic patients, concomitant diuretics, dialysis, or during major surgery

Renal deterioration may occur

Discontinue immediately with pregnancy (see Black Box Warnings)

Caution in patients with CHF; may need to adjust dose

Hyperkalemia may occur with renal failure or drugs that increase potassium levels; monitor serum potassium levels periodically

Dual blockade of the renin angiotensin system with ARBs, ACE inhibitors, or aliskiren associated with increased risk for renal function changes (including acute renal failure) compared to monotherapy

Risk of anaphylactoid reactions and/or angioedema

Caution in hepatic impairment, hypercholesterolemia, hypercalcemia, parathyroid disease, pre-existing renal insufficiency, systemic lupus erythematosus, anuria

Caution in patients with aortic/mitral stenosis

Caution in patients with unstented unilateral/bilateral artery stenosis

Infants <1year must not receive candesartan; may have effects on the development of immature kidneys

In-utero exposure in neonates: If oliguria or hypotension occur, exchange transfusions or dialysis may be required to reverse hypotension and/or substitute for disordered renal function

Pregnancy

Therapy can cause fetal harm when administered to a pregnant woman; use of drugs that act on renin-angiotensin system during second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death

Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents;

when pregnancy is detected, discontinue drug as soon as possible

Disease-associated maternal/embryo/fetal risk

• Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage)
• Hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly
• Pregnant women with chronic heart failure are at increased risk for preterm birth; stroke volume and heart rate increase during pregnancy, increasing cardiac output, especially during the first trimester
• Heart failure may worsen with pregnancy and may lead to maternal death; closely monitor pregnant patients for destabilization of their heart failure
• Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death
• In the unusual case that there is no appropriate alternative to therapy with drugs affecting renin-angiotensin system for a particular patient, apprise the mother of the potential risk to fetus
• Perform serial ultrasound examinations to assess intra-amniotic environment; fetal testing may be appropriate, based on the week of pregnancy; patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury; if oligohydramnios is observed, consider alternative drug treatment
• Closely observe infants with histories of in utero exposure to drug for hypotension, oliguria, hyperkalemia or other symptoms of renal impairment; in neonates with a history of in utero exposure, if oliguria or hypotension occurs, support blood pressure and renal perfusion; exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function

Lactation

Not known whether drug is excreted in human milk, but shown to be present in rat milk; because of potential for serious adverse reactions in breastfed infants, advise a nursing woman that breastfeeding is not recommended during therapy

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Angiotensin II receptor blocker (ARB); prevents angiotensin II from binding to its receptor, which in turn blocks the vasoconstriction and aldosterone secreting effects of angiotensin II.

Pharmacokinetics

Half-Life: 5-9 hr

Peak Plasma Time: 3-4 hr

Metabolism: Liver (minimal)

Excretion: Urine (26%)

Dialyzable: No (HD)

Bioavailability: 15%

Onset of action: 2-3 hr

Peak effect: 6-8hr

Duration: >24hr

Vd: 0.13 L/kg

Protein binding: >99%