ATACAND
Generic: CANDESARTAN CILEXETIL
Basic Information
Manufacturer
ANI Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
94a59260-d2b6-464a-b5b9-bbc599e57e10
Indications & Usage
1 INDICATIONS AND USAGE ATACAND is an angiotensin II receptor blocker (ARB) indicated for: • Treatment of hypertension in adults and children 1 to < 17 years of age, to lower blood pressure.
Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions (1.1) .
• Treatment of heart failure (NYHA class II-IV); ATACAND reduces cardiovascular death and heart failure hospitalization (1.2) .
1.1 Hypertension ATACAND is indicated for the treatment of hypertension in adults and in children 1 to <17 years of age, to lower blood pressure.
Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.
These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.
Many patients will require more than one drug to achieve blood pressure goals.
For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits.
The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit.
Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease).
These considerations may guide selection of therapy.
ATACAND may be used alone or in combination with other antihypertensive agents.
1.2 Heart Failure ATACAND is indicated for the treatment of heart failure (NYHA class II-IV) in adults with left ventricular systolic dysfunction (ejection fraction ≤ 40%) to reduce cardiovascular death and to reduce heart failure hospitalizations [see Clinical Studies (14.2) ] .
ATACAND also has an added effect on these outcomes when used with an ACE inhibitor [see Drug Interactions (7.4) ] .
Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions (1.1) .
• Treatment of heart failure (NYHA class II-IV); ATACAND reduces cardiovascular death and heart failure hospitalization (1.2) .
1.1 Hypertension ATACAND is indicated for the treatment of hypertension in adults and in children 1 to <17 years of age, to lower blood pressure.
Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions.
These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including the class to which this drug principally belongs.
Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.
Many patients will require more than one drug to achieve blood pressure goals.
For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).
Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits.
The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.
Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit.
Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.
Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease).
These considerations may guide selection of therapy.
ATACAND may be used alone or in combination with other antihypertensive agents.
1.2 Heart Failure ATACAND is indicated for the treatment of heart failure (NYHA class II-IV) in adults with left ventricular systolic dysfunction (ejection fraction ≤ 40%) to reduce cardiovascular death and to reduce heart failure hospitalizations [see Clinical Studies (14.2) ] .
ATACAND also has an added effect on these outcomes when used with an ACE inhibitor [see Drug Interactions (7.4) ] .
Adverse Reactions
6 ADVERSE REACTIONS • Most common adverse reactions which caused adult patients to discontinue therapy for: • Hypertension were headache (0.6%) and dizziness (0.3%) (6.1) .
• Heart Failure were hypotension (4.1%) (5.3) , abnormal renal function (6.3%) (5.4) , and hyperkalemia (2.4%) (5.5) .
To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc.
at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Adult Hypertension ATACAND has been evaluated for safety in more than 3600 patients/subjects, including more than 3200 patients treated for hypertension.
About 600 of these patients were studied for at least 6 months and about 200 for at least 1 year.
In general, treatment with ATACAND was well tolerated.
The overall incidence of adverse events reported with ATACAND was similar to placebo.
The rate of withdrawals due to adverse events in all trials in patients (7510 total) was 3.3% (i.e., 108 of 3260) of patients treated with ATACAND as monotherapy and 3.5% (i.e., 39 of 1106) of patients treated with placebo.
In placebo-controlled trials, discontinuation of therapy due to clinical adverse events occurred in 2.4% (i.e., 57 of 2350) of patients treated with ATACAND and 3.4% (i.e., 35 of 1027) of patients treated with placebo.
The most common reasons for discontinuation of therapy with ATACAND were headache (0.6%) and dizziness (0.3%).
The adverse events that occurred in placebo-controlled clinical trials in at least 1% of patients treated with ATACAND and at a higher incidence in candesartan cilexetil (n = 2350) than placebo (n = 1027) patients included back pain (3% vs.
2%), dizziness (4% vs.
3%), upper respiratory tract infection (6% vs.
4%), pharyngitis (2% vs.
1%), and rhinitis (2% vs.
1%).
Pediatric Hypertension Among children in clinical studies, 1 in 93 children age 1 to < 6 and 3 in 240 age 6 to < 17 experienced worsening renal disease.
The association between candesartan and exacerbation of the underlying condition could not be excluded.
Heart Failure The adverse event profile of ATACAND in adult heart failure patients was consistent with the pharmacology of the drug and the health status of the patients.
In the CHARM program, comparing ATACAND in total daily doses up to 32 mg once daily (n=3803) with placebo (n=3796), 21.0% of patients discontinued ATACAND for adverse events vs.
16.1% of placebo patients.
6.2 Postmarketing Experience The following adverse reactions were identified during post-approval use of ATACAND.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following have been very rarely reported in post-marketing experience: 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 in patients receiving angiotensin II receptor blockers.
• Heart Failure were hypotension (4.1%) (5.3) , abnormal renal function (6.3%) (5.4) , and hyperkalemia (2.4%) (5.5) .
To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc.
at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Studies Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Adult Hypertension ATACAND has been evaluated for safety in more than 3600 patients/subjects, including more than 3200 patients treated for hypertension.
About 600 of these patients were studied for at least 6 months and about 200 for at least 1 year.
In general, treatment with ATACAND was well tolerated.
The overall incidence of adverse events reported with ATACAND was similar to placebo.
The rate of withdrawals due to adverse events in all trials in patients (7510 total) was 3.3% (i.e., 108 of 3260) of patients treated with ATACAND as monotherapy and 3.5% (i.e., 39 of 1106) of patients treated with placebo.
In placebo-controlled trials, discontinuation of therapy due to clinical adverse events occurred in 2.4% (i.e., 57 of 2350) of patients treated with ATACAND and 3.4% (i.e., 35 of 1027) of patients treated with placebo.
The most common reasons for discontinuation of therapy with ATACAND were headache (0.6%) and dizziness (0.3%).
The adverse events that occurred in placebo-controlled clinical trials in at least 1% of patients treated with ATACAND and at a higher incidence in candesartan cilexetil (n = 2350) than placebo (n = 1027) patients included back pain (3% vs.
2%), dizziness (4% vs.
3%), upper respiratory tract infection (6% vs.
4%), pharyngitis (2% vs.
1%), and rhinitis (2% vs.
1%).
Pediatric Hypertension Among children in clinical studies, 1 in 93 children age 1 to < 6 and 3 in 240 age 6 to < 17 experienced worsening renal disease.
The association between candesartan and exacerbation of the underlying condition could not be excluded.
Heart Failure The adverse event profile of ATACAND in adult heart failure patients was consistent with the pharmacology of the drug and the health status of the patients.
In the CHARM program, comparing ATACAND in total daily doses up to 32 mg once daily (n=3803) with placebo (n=3796), 21.0% of patients discontinued ATACAND for adverse events vs.
16.1% of placebo patients.
6.2 Postmarketing Experience The following adverse reactions were identified during post-approval use of ATACAND.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following have been very rarely reported in post-marketing experience: 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 in patients receiving angiotensin II receptor blockers.