EDARBYCLOR- azilsartan kamedoxomil and chlorthalidone tablet

Država: Sjedinjene Američke Države

Jezik: engleski

Izvor: NLM (National Library of Medicine)

Aktivni sastojci:

AZILSARTAN KAMEDOXOMIL (UNII: WEC6I2K1FC) (AZILSARTAN - UNII:F9NUX55P23), CHLORTHALIDONE (UNII: Q0MQD1073Q) (CHLORTHALIDONE - UNII:Q0MQD1073Q)

Dostupno od:

Pharma Packaging Solutions, LLC dba Tjoapack LLC

Administracija rute:

ORAL

Tip recepta:

PRESCRIPTION DRUG

Terapijske indikacije:

Edarbyclor is indicated for the treatment of hypertension, to lower blood pressure. Edarbyclor may be used in patients whose blood pressure is not adequately controlled on monotherapy. Edarbyclor may be used as initial therapy if a patient is likely to need multiple drugs to achieve blood pressure goals. Lowering blood pressure reduces the risk of fatal and nonfatal 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 thiazide-like diuretics such as chlorthalidone and ARBs such as azilsartan medoxomil. There are no controlled trials demonstrating risk reduction with Edarbyclor. 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 of high blood pressure, 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; however, the blood pressure effect of Edarbyclor in blacks is similar to that in non-blacks. 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. The choice of Edarbyclor as initial therapy for hypertension should be based on an assessment of potential benefits and risks including whether the patient is likely to tolerate the starting dose of Edarbyclor. Patients with moderate-to-severe hypertension are at a relatively high risk of cardiovascular events (e.g., stroke, heart attack, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. Consider the patient's baseline blood pressure, target goal and the incremental likelihood of achieving the goal with a combination product, such as Edarbyclor, versus a monotherapy product when deciding upon initial therapy. Individual blood pressure goals may vary based on the patient's risk. Data from an 8-week, active-controlled, factorial trial provide estimates of the probability of reaching a target blood pressure with Edarbyclor compared with azilsartan medoxomil or chlorthalidone monotherapy [see Clinical Studies (14)] . Figures 1.a-1.d provide estimates of the likelihood of achieving target clinic systolic and diastolic blood pressure control with Edarbyclor 40/25 mg tablets after 8 weeks, based on baseline systolic or diastolic blood pressure. The curve for each treatment group was estimated by logistic regression modeling and is more variable at the tails. For example, a patient with a baseline blood pressure of 170/105 mm Hg has approximately a 48% likelihood of achieving a goal of <140 mm Hg (systolic) and 48% likelihood of achieving <90 mm Hg (diastolic) on azilsartan medoxomil 80 mg. The likelihood of achieving these same goals on chlorthalidone 25 mg is approximately 51% (systolic) and 40% (diastolic). These likelihoods rise to 85% (systolic) and 85% (diastolic) with Edarbyclor 40/25 mg. - Edarbyclor is contraindicated in patients with anuria [see Warnings and Precautions (5.3)]. - Do not coadminister aliskiren-containing products with Edarbyclor in patients with diabetes [see Drug Interactions (7)] . Risk Summary Edarbyclor can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death ( see Clinical Considerations ). Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. When pregnancy is detected, discontinue Edarbyclor as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly. Fetal/Neonatal adverse reactions Oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters 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. Perform serial ultrasound examinations to assess the 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. Closely observe infants with histories of in utero exposure to Edarbyclor for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to Edarbyclor, 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/or substituting for disordered renal function . Chlorthalidone Thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possible other adverse reactions that have occurred in adults. Data Animal Data Edarbyclor The safety profiles of azilsartan medoxomil and chlorthalidone monotherapy have been individually established. To characterize the toxicological profile for Edarbyclor, a 13-week repeat-dose toxicity study was conducted in rats. The results of this study indicated that the combined administration of azilsartan medoxomil, M-II, and chlorthalidone resulted in increased exposures to chlorthalidone. Pharmacologically-mediated toxicity, including suppression of body weight gain and decreased food consumption in male rats, and increases in blood urea nitrogen in both sexes, was enhanced by coadministration of azilsartan medoxomil, M-II, and chlorthalidone. With the exception of these findings, there were no toxicologically synergistic effects in this study. In an embryo-fetal developmental study in rats, there was no teratogenicity or increase in fetal mortality in the litters of dams receiving azilsartan medoxomil, M-II and chlorthalidone concomitantly at maternally toxic doses. Azilsartan medoxomil Reproductive Toxicology: In peri- and postnatal rat development studies, adverse effects on pup viability, delayed incisor eruption and dilatation of the renal pelvis along with hydronephrosis were seen when azilsartan medoxomil was administered to pregnant and nursing rats at 1.2 times the MRHD on a mg/m 2 basis. Reproductive toxicity studies indicated that azilsartan medoxomil was not teratogenic when administered at oral doses up to 1000 mg azilsartan medoxomil/kg/day to pregnant rats (122 times the MRHD on a mg/m 2 basis) or up to 50 mg azilsartan medoxomil/kg/day to pregnant rabbits (12 times the MRHD on a mg/m 2 basis). M-II also was not teratogenic in rats or rabbits at doses up to 3000 mg M-II/kg/day. Azilsartan crossed the placenta and was found in the fetuses of pregnant rats and was excreted into the milk of lactating rats. Chlorthalidone Reproductive toxicology: Reproduction studies have been performed in the rat and the rabbit at doses up to 420 times the human dose and have revealed no evidence of harm to the fetus. Thiazides cross the placental barrier and appear in cord blood. Risk Summary There is limited information regarding the presence of azilsartan in human milk, the effects on the breastfed infant, or the effects on milk production. Azilsartan is present in rat milk. Thiazide-like diuretics like chlorthalidone are excreted in human milk. Because of the potential for adverse effects on the nursing infant, advise a nursing woman that breastfeeding is not recommended during treatment with Edarbyclor . Safety and effectiveness of Edarbyclor in pediatric patients under 18 years of age have not been established. Edarbyclor No dose adjustment with Edarbyclor is necessary in elderly patients. Of the total patients in clinical studies with Edarbyclor, 24% were elderly (65 years of age or older); 5.7% were 75 years and older. No overall differences in safety or effectiveness were observed between elderly patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)]. Edarbyclor Safety and effectiveness of Edarbyclor in patients with severe renal impairment (eGFR <30 mL/min/1.73 m 2 ) have not been established. No dose adjustment is required in patients with mild (eGFR 60-90 mL/min/1.73 m 2 ) or moderate (eGFR 30-60 mL/min/1.73 m 2 ) renal impairment. Chlorthalidone Chlorthalidone may precipitate azotemia. Azilsartan medoxomil No dose adjustment is necessary for subjects with mild or moderate hepatic impairment. Azilsartan medoxomil has not been studied in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)]. Chlorthalidone Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.

Proizvod sažetak:

Edarbyclor is supplied as fixed dose combination tablets that are round, biconvex, film-coated, and 9.7 mm in diameter. Store at 25°C (77°F), excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Keep container tightly closed. Protect from moisture and light. Do not repackage; dispense and store in original container.

Status autorizacije:

New Drug Application

Svojstava lijeka

EDARBYCLOR- AZILSARTAN KAMEDOXOMIL AND CHLORTHALIDONE TABLET
PHARMA PACKAGING SOLUTIONS, LLC DBA TJOAPACK LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
EDARBYCLOR (AZILSARTAN MEDOXOMIL AND CHLORTHALIDONE) TABLETS, FOR ORAL
USE
(PACKAGED BY PHARMA PACKAGING SOLUTIONS, LLC DBA TJOAPACK LLC)
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
EDARBYCLOR SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR EDARBYCLOR.
INITIAL U.S. APPROVAL: 2011
WARNING: FETAL TOXICITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
WHEN PREGNANCY IS DETECTED, DISCONTINUE EDARBYCLOR AS SOON AS POSSIBLE
( 5.1,
8.1)
DRUGS THAT ACT DIRECTLY ON THE RENIN-ANGIOTENSIN SYSTEM CAN CAUSE
INJURY AND DEATH
TO THE DEVELOPING FETUS ( 5.1, 8.1)
INDICATIONS AND USAGE
Edarbyclor is a combination of azilsartan medoxomil, an angiotensin II
receptor blocker (ARB) and
chlorthalidone, a thiazide-like diuretic combination product indicated
for the treatment of hypertension, to
lower blood pressure:
In patients not adequately controlled with monotherapy ( 1)
As initial therapy in patients likely to need multiple drugs to help
achieve blood pressure goals ( 1)
Lowering blood pressure reduces the risk of fatal and nonfatal
cardiovascular events, primarily strokes and
myocardial infarctions ( 1)
DOSAGE AND ADMINISTRATION
Starting dose is 40/12.5 mg once daily ( 2.1)
Edarbyclor may be used to provide additional blood pressure lowering
for patients not adequately
controlled on azilsartan medoxomil 80 mg or chlorthalidone 25 mg (
2.1)
Dose may be increased to 40/25 mg after 2 to 4 weeks as needed to
achieve blood pressure goals (
2.1)
Maximal dose is 40/25 mg ( 2.1)
May be administered with other antihypertensive agents ( 2.1)
Edarbyclor may be administered with or without food ( 2.1)
Replace volume in volume-depleted patients prior to use ( 2.2)
DOSAGE FORMS AND STRENGTHS
Tablets (azilsartan/chlorthalidone): 40/12.5 mg and 40/25 mg ( 3)
CONTRAINDICATIONS
Anuria ( 4)
Do not coadminister aliskiren-containing products wi