AMLODIPINE, VALSARTAN, HYDROCHLOROTHIAZIDE- amlodipine besylate valsartan hydrochlorothiazide tablet, film coated

Ország: Egyesült Államok

Nyelv: angol

Forrás: NLM (National Library of Medicine)

Aktív összetevők:

AMLODIPINE BESYLATE (UNII: 864V2Q084H) (AMLODIPINE - UNII:1J444QC288), VALSARTAN (UNII: 80M03YXJ7I) (VALSARTAN - UNII:80M03YXJ7I), HYDROCHLOROTHIAZIDE (UNII: 0J48LPH2TH) (HYDROCHLOROTHIAZIDE - UNII:0J48LPH2TH)

Beszerezhető a:

Strides Pharma Science Limited

Az alkalmazás módja:

ORAL

Recept típusa:

PRESCRIPTION DRUG

Terápiás javallatok:

Amlodipine/valsartan/hydrochlorothiazide is indicated for the treatment of hypertension, to lower blood pressure. 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 amlodipine, hydrochlorothiazide, and the ARB class to which valsartan principally belongs. There are no controlled trials demonstrating risk reduction with amlodipine/valsartan/hydrochlorothiazide. 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 1 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 (e.g., 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. Limitation of Use Amlodipine/valsartan/hydrochlorothiazide is not indicated for the initial therapy of hypertension [see Dosage and Administration (2)]. Do not use in patients with anuria, hypersensitivity to other sulfonamide-derived drugs, or hypersensitivity to any component of this product. Do not coadminister aliskiren with amlodipine/valsartan/hydrochlorothiazide in patients with diabetes [see Drug Interactions (7)]. Risk Summary Amlodipine/valsartan/hydrochlorothiazide 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. 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. Published reports include cases of anhydramnios and oligohydramnios in pregnant women treated with valsartan (see Clinical Considerations). When pregnancy is detected, discontinue Amlodipine/valsartan/hydrochlorothiazide 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 Valsartan 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. Perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. 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 neonates with histories of in utero exposure to Amlodipine/valsartan/hydrochlorothiazide for hypotension, oliguria, and hyperkalemia. In neonates with a history of in utero exposure to Amlodipine/valsartan/hydrochlorothiazide, 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. Hydrochlorothiazide Thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. Hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion. It accumulates in the amniotic fluid, with reported concentrations up to 19 times higher than in umbilical vein plasma. Use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. Since they do not prevent or alter the course of EPH (Edema, Proteinuria, Hypertension) gestosis (preeclampsia), these drugs should not be used to treat hypertension in pregnant women. The use of HCTZ for other indications (e.g., heart disease) in pregnancy should be avoided. Data Animal Data Valsartan and Amlodipine In rats, administered 20 mg/kg/day amlodipine plus 320 mg/kg/day valsartan, treatment-related maternal and fetal effects (developmental delays and alterations noted in the presence of significant maternal toxicity) were noted with the high dose combination. This corresponds to dose multiples of 9 and 19.5 times, respectively, the maximum recommended human dose (MRHD) of 10 mg/day for amlodipine and 320 mg/day for valsartan (based on body surface area and considering a 60 kg patient). Hydrochlorothiazide No teratogenic effects were observed when hydrochlorothiazide was administered to mice and rats via gavage at doses of up to 3,000 and 1,000 mg/kg/day (608 and 405 times the MRHD), on gestation days 6 through 15. Risk Summary There is limited information regarding the presence of Amlodipine/valsartan/hydrochlorothiazide in human milk, the effects on the breastfed infant, or the effects on milk production. Hydrochlorothiazide is present in human milk and valsartan is present in rat milk. Limited published studies report that amlodipine is present in human milk. Because of the potential for serious adverse reactions in breastfed infants, advise a nursing woman that breastfeeding is not recommended during treatment with Amlodipine/valsartan/hydrochlorothiazide. Data Valsartan was detected in the milk of lactating rats 15 minutes after oral administration of a 3 mg/kg dose. The safety and effectiveness of amlodipine/valsartan/hydrochlorothiazide in pediatric patients have not been established. Amlodipine Clinical studies of amlodipine besylate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40% to 60% [see Clinical Pharmacology (12.3)] . The recommended starting dose of amlodipine 2.5 mg is not an available strength with amlodipine/valsartan/hydrochlorothiazide [see Clinical Studies (14)]. Safety and effectiveness of amlodipine/valsartan/hydrochlorothiazide in patients with severe renal impairment (CrCl < 30 mL/min) have not been established. No dose adjustment is required in patients with mild (CrCl 60 to 90 mL/min) or moderate (CrCl 30 to 60 mL/min) renal impairment. Amlodipine Exposure to amlodipine is increased in patients with hepatic insufficiency.  The recommended initial dose of amlodipine in patients with hepatic impairment is 2.5 mg, which is not an available strength with amlodipine/valsartan/hydrochlorothiazide [see Clinical Pharmacology (12.3)]. Valsartan No dose adjustment is necessary for patients with mild-to-moderate disease. No dosing recommendations can be provided for patients with severe liver disease. Hydrochlorothiazide Minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.

Termék összefoglaló:

Amlodipine/valsartan/hydrochlorothiazide is available as film-coated tablets containing amlodipine besylate equivalent to 5 mg or 10 mg of amlodipine free-base with valsartan 160 mg or 320 mg and hydrochlorothiazide 12.5 mg or 25 mg providing for the following available combinations: 5/160/12.5 mg, 10/160/12.5 mg, 5/160/25 mg, 10/160/25 mg or 10/320/25 mg. All strengths are packaged in bottles of 30, 90 and 500 tablets. 5 mg amlodipine /160 mg valsartan /12.5 mg hydrochlorothiazide Tablets - White to off-white, film coated, oval shaped biconvex tablets, debossed with "P" on one side of the tablet and "172" on the other                                                                   Bottles of 30                                                NDC 64380-197-01                                                                   Bottles of 90                                                NDC 64380-197-02                                                                   Bottles of 500                                              NDC 64380-197-03 10 mg amlodipine /160 mg valsartan /12.5 mg hydrochlorothiazide Tablets – Peach to light brown, film coated, oval shaped biconvex tablets, debossed with "P" on one side of the tablet and "174" on the other.                                                                  Bottles of 30                                                 NDC 64380-199-01                                                                  Bottles of 90                                                 NDC 64380-199-02                                                                  Bottles of 500                                               NDC 64380-199-03  5 mg amlodipine /160 mg valsartan /25 mg hydrochlorothiazide Tablets – Yellow, film-coated, oval shaped biconvex tablets debossed with "P" on one side of the tablet and "173" on the other.                                                                Bottles of 30                                                   NDC 64380-198-01                                                                Bottles of 90                                                   NDC 64380-198-02                                                                Bottles of 500                                                 NDC 64380-198-03 10 mg amlodipine /160 mg valsartan /25 mg hydrochlorothiazide Tablets – Bright yellow, film-coated oval shaped, biconvex tablets debossed with "P" on one side of the tablet and "185" on the other.                                                                 Bottles of 30                                                   NDC 64380-200-01                                                                 Bottles of 90                                                   NDC 64380-200-02                                                                 Bottles of 500                                                 NDC 64380-200-03 10 mg amlodipine /320 mg valsartan /25 mg hydrochlorothiazide Tablets – White to off-white, film coated, oval shaped biconvex tablets, debossed with "P" on one side of the tablet and "175" on the other                                                                 Bottles of 30                                                    NDC 64380-201-01                                                                 Bottles of 90                                                    NDC 64380-201-02                                                                 Bottles of 500                                                  NDC 64380-201-03 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15º to 30°C (59º to 86°F) [see USP Controlled Room Temperature.] Protect from moisture. Dispense in tight container (USP).

Engedélyezési státusz:

Abbreviated New Drug Application

Termékjellemzők

AMLODIPINE, VALSARTAN, HYDROCHLOROTHIAZIDE - AMLODIPINE BESYLATE
VALSARTAN HYDROCHLOROTHIAZIDE TABLET, FILM COATED
AMLODIPINE, VALSARTAN, HYDROCHLOROTHIAZIDE - AMLODIPINE BESYLATE
VALSARTAN HYDROCHLOROTHIAZIDE TABLET, FILM COATED
STRIDES PHARMA SCIENCE LIMITED
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
AMLODIPINE/VALSARTAN/HYDROCHLOROTHIAZIDE SAFELY AND EFFECTIVELY. SEE
FULL
PRESCRIBING INFORMATION FOR AMLODIPINE/VALSARTAN/HYDROCHLOROTHIAZIDE.
AMLODIPINE/VALSARTAN/HYDROCHLOROTHIAZIDE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2009
WARNING: FETAL TOXICITY
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
• WHEN PREGNANCY IS DETECTED, DISCONTINUE
AMLODIPINE/VALSARTAN/HYDROCHLOROTHIAZIDE
AS SOON AS POSSIBLE. (5.1)
• DRUGS THAT ACT DIRECTLY ON THE RENIN-ANGIOTENSIN SYSTEM CAN CAUSE
INJURY AND DEATH TO
THE DEVELOPING FETUS. (5.1)
INDICATIONS AND USAGE
Amlodipine/valsartan/hydrochlorothiazide is a combination tablet of
amlodipine, a dihydropyridine
calcium channel blocker (DHP CCB), valsartan, an angiotensin II
receptor blocker (ARB), and
hydrochlorothiazide, a thiazide diuretic.
Amlodipine/Valsartan/Hydrochlorothiazide is indicated for the
treatment of hypertension to lower blood pressure. Lowering blood
pressure reduces the risk of fatal
and nonfatal cardiovascular events, primarily strokes, and myocardial
infarctions. (1)
Limitation of Use (1)
Amlodipine/valsartan/hydrochlorothiazide is not indicated for initial
treatment of hypertension. (1)
DOSAGE AND ADMINISTRATION
Dose once-daily. Titrate up to a maximum dose of 10/320/25 mg. (2.1)
Amlodipine/valsartan/hydrochlorothiazide may be used as add-on/switch
therapy for patients not
adequately controlled on any two of the following antihypertensive
classes: calcium channel blockers,
angiotensin receptor blockers, and diuretics. (2.2)
Amlodipine/valsartan/hydrochlorothiazide may be substituted for its
individually titrated components.
(2.3)
DOSAGE FORMS AND STRENGTHS
Tablets: (amlo