Finil

Finil

candesartan

Manufacturer:

Unison

Distributor:

Medline

Marketer:

Medline
Full Prescribing Info
Contents
Candesartan cilexetil.
Action
Pharmacotherapeutic Group: Angiotensin II Receptor Blocker; Antihypertensive.
Pharmacology: Pharmacodynamics:
Mechanism of Action: 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.
Pharmacodynamics/kinetics: Onset of Action: 2-3 hours.
Peak Effect: 6-8 hours.
Distribution: Vd: 0.13 L/kg.
Protein binding: >99%.
Metabolism: Parent compound bioactivated during absorption via ester hydrolysis within intestinal wall to candesartan.
Bioavailability: 15%.
Half-life Elimination (dose dependent): 5-9 hours.
Time to peak: 3 to 4 hours.
Excretion: Urine (26%).
Indications/Uses
Heart Failure: Treatment of heart failure (NYHA class II-IV).
Note: The ACCF/AHA 2013 heart failure guidelines recommend the use of ARBs (ie, candesartan, losartan, and valsartan) in patients with HF with reduced ejection fraction who cannot tolerate ACE inhibitors (due to cough) to reduce morbidity and mortality. They also suggest that ARBs are reasonable first-line alternatives to ACE inhibitors in patients already maintained on an ARB for other indications.
Hypertension: Alone or in combination with other anti­hypertensive agents ill treating hypertension.
Dosage/Direction for Use
Hypertension: Note: Antihypertensive effect usually observed within 2 weeks; maximum antihypertensive effect seen within 4 to 6 weeks. Consider lower initial dosages in volume depleted patients; if possible, correct volume depletion prior to administration.
Use in children <6 years is not approved in the Canadian labeling.
Children 1 to <6 years: Oral: Initial: 0.2 mg/kg/day in 1 to 2 divided doses; titrate to response; usual range: 0.05 to 0.4 mg/kg/day; maximum daily dose: 0.4 mg/kg/day.
Children ≥6 years and Adolescents <17 years: Oral: U.S labeling: <50 kg: Initial: 4 to 8 mg daily in 1 to 2 divided doses; titrate to response; usual range: 2 to 16 mg daily; maximum daily dose: 32 mg daily.
≥50 kg: Initial: 8 to 16 mg daily in 1 to 2 divided doses; titrate to response; usual range: 4 to 32 mg daily; maximum daily dose: 32 mg daily.
Canadian labeling: <50 kg: Initial: 4 mg once daily; titrate to response; maximum dose: 8 mg daily.
50 kg: Initial: 8 mg once daily; titrate to response; maximum dose: 16 mg daily.
Adults: Oral: Dosage must be individualized. Initial: 16 mg once daily; titrate to response; usual range: 8 to 32 mg daily in 1 to 2 divided doses; target dose: 12 to 32 mg daily; maximum daily dose: 32 mg daily.
Heart failure: Adults: Oral: Initial: 4 mg once daily (U.S. labeling) or alternatively 4 to 8 mg once daily (ACCF/AHA); double the dose at 2-week intervals as tolerated; target dose: 32 mg once daily (ACCF/AHA).
Note: Concurrent therapy with an ACE inhibitor may provide additional benefit in patients with HF with reduced EF who remain symptomatic on standard therapy and are unable to receive an aldosterone antagonist (ACCF/AHA).
Canadian labeling: Initial: 4 mg once daily; double the dose at 2-week intervals as tolerated; target dose: 32 mg once daily Elderly: No initial dosage adjustment is necessary for elderly patients (although higher concentrations (Cmax) and AUC were observed in this population).
Dosage adjustment in renal impairment: U.S. labeling: Children ≥1 year and Adolescents <17 years: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied). Children with GFR <30 mL/minute/1.73 m2 should not receive cande­sartan.
Adults: No initial dosage adjustment necessary; how­ever, in patients with severe renal impairment (CrCl <30 ml/minute/1.73 m2) AUC and Cmax were approx­imately doubled after repeated dosing.
Canadian labeling: Children ≥6 and Adolescents ≤17 years: There are no dosage adjustments provided in manufacturer's label­ing (has not been studied).
Adults: Mild impairment: No dosage adjustment necessary.
Moderate or severe impairment: Consider initial dose of 4 mg once daily in patients with hypertension.
Dialysis: Consider initial dose of 4 mg once daily in patients with hypertension.
Dosage adjustment in hepatic impairment: U.S. labeling: Mild impairment (Child-Pugh class A): No initial dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Initial: 8 mg daily (AUC increased by 145%) in adult patients with hypertension. There are no dosage adjustments pro­vided in the manufacturer's labeling for pediatric patients.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, systemic exposure increases significantly in moderate impairment.
Contraindications
Hypersensitivity to candesartan or any component of the formulation; concomitant use with aliskiren in patients with diabetes mellitus.
Special Precautions
Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
May cause hyperkalemia; avoid potassium supplementation unless specifically required by healthcare provider. Avoid use or use a smaller dose in patients who are volume depleted; correct depletion first. May be associated with deterioration of renal function and/or increases in serum creatinine, particularly in patients with low renal blood flow (eg, renal artery stenosis, heart failure) whose glomerular filtration rate (GFR) is dependent on efferent arteriolar vasoconstriction by angiotensin II; deterioration may result in oliguria, acute renal failure, and progressive azotermia. Small increases in serum creatinine may occur following initiation; consider discontinuation only in patients will progressive and/or significant deterioration in renal function. Use with caution in unstented unilateral/bilateralrenal artery stenosis, preexisting renal insufficiency, or significant aortic/mitral stenosis. Systemic exposure increases in hepatic impairment. U.S. manufacturer labeling recommends a dosage adjustment in patients with moderate hepatic impairment; pharmacokinetics have not been studied in severe hepatic impairment. Use caution when initiating in heart failure; may need to adjust dose, and/or concurrent diuretic therapy, because of candesartan­ induced hypotension. In surgical patients on chronic angiotensin receptor blocker (ARB) therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia. Potentially significant drug-drug inte­ractions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Pediatric patients with a GFR <30 mL/minute/1.73 m2 should not receive candesartan; has not been evaluated. Avoid use in infants <1 year of age due to potential effects on the development of immature kidneys.
Use In Pregnancy & Lactation
Use in Pregnancy: Pregnancy Risk Factor: D.
Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Dis­continue as soon as possible once pregnancy is detected.
The use of drugs which act on the renin-angio­tensin system are associated with oligohydramnios. Oligo­hydramnios, due to decreased fetal renal function, may lead to fetal lung hypoplasia and skeletal malformations. Use is also associated with anuria, hypotension, renal failure, skull hypoplasia, and death in the fetus/neonate.
The exposed fetus should be monitored for fetal growth, amniotic fluid volume, and organ formation. Infants exposed in utero should be monitored for hyperkalemia, hypotension, and oliguria (exchange transfusions or dialy­sis may be needed). These adverse events are generally associated with maternal use in the second and third trimesters.
Untreated chronic maternal hypertension is also associ­ated with adverse events in the fetus, infant, and mother. The use of angiotensin II receptor blockers is not recommended to treat chronic uncomplicated hypertension in pregnant women and should generally be avoided in women of reproductive potential.
Use in Lactation:
It is not known if can­desartan is excreted into breast milk. Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.
Adverse Reactions
Cardiovascular: Angina pectoris, hypotension, myocardial infarction, palpitations, tachycardia.
Central nervous system: Anxiety, depression, dizziness, drowsiness, headache, paresthesia, vertigo.
Dermatologic: Diaphoresis, skin rash.
Endocrine and metabolic: Hyperglycemia, hyperkalemia, hypertriglyceridemia, hyperuricemia.
Gastrointestinal: Dyspepsia, gastroenteritis.
Genitourinary: Hematuria.
Neuromuscular and skeletal: Back pain, increased creatinine phosphokinase, myalgia, weakness.
Renal: Increased serum creatinine.
Respiratory: Dyspnea, epistaxis, pharyngitis, rhinitis, upper respiratory tract infection.
Miscellaneous: Fever.
Rare but important or life-threatening: Atrial fibrillation, bradycardia, cardiac failure, cerebrovascular accident, confusion, hepatic insufficiency, hepatitis, hypersensitivity, leukopenia, loss of consciousness, pancreatitis, pneumonia, presyncope, pulmonary edema, renal failure, rhabdomyolysis, thrombocytopenia.
Drug Interactions
Metabolism/Transport Effects Substrate of CYP2C9 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential. Inhibits CYP2C8 (weak), CYP2C9 (weak).
Avoid Concomitant Use: There are no known interactions where it is recommended to avoid concomitant use.
Increased Effect/Toxicity: Candesartan may increase the levels/effects of: ACE inhibitors; amifostine; antihypertensives; cyclosporine (systemic); Duloxetine; hypotensive agents; levodopa; lithium; non-steroidal anti-inflammatory agents; obinutuzumab; potassium-sparing diuretics; risperidone; rituximab; sodium phosphates.
The levels/effects of Candesartan may be increased by: Alfuzosin; Aliskiren; Barbiturates; Brimonidine (topical); canagliflozin; dapoxetine; diazoxide; eplerenone; heparin; heparin (low molecular weight); herbs (hypotensive properties); MAO inhibitors; nicorandil; pentoxifylline; phosphodiesterase 5 inhibitors; potassium salts; prostacyclin analogues; tolvaptan; trimethoprim.
Decreased effect: The levels/effects of candesartan may be decreased by Herbs (Hypertensive properties); methylphenidate; non-steroidal anti-inflammatory agents; yohimbine.
Storage
Store under 30°C.
ATC Classification
C09CA06 - candesartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
Presentation/Packing
Tab 8 mg x 10 x 10's, 16 mg x 10 x 10's.
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