METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE tablet

Země: Spojené státy

Jazyk: angličtina

Zdroj: NLM (National Library of Medicine)

Aktivní složka:

METOPROLOL TARTRATE (UNII: W5S57Y3A5L) (METOPROLOL - UNII:GEB06NHM23), HYDROCHLOROTHIAZIDE (UNII: 0J48LPH2TH) (HYDROCHLOROTHIAZIDE - UNII:0J48LPH2TH)

Dostupné s:

Alembic Pharmaceuticals Inc.

INN (Mezinárodní Name):

METOPROLOL TARTRATE

Složení:

METOPROLOL TARTRATE 50 mg

Podání:

ORAL

Druh předpisu:

PRESCRIPTION DRUG

Terapeutické indikace:

Metoprolol tartrate and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure lowers 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 metoprolol. 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 (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. Metoprolol tartrate and hydrochlorothiazide tablets may be administered with other antihypertensive agents. Limitation of Use Metoprolol tartrate and hydrochlorothiazide tablets are not indicated for initial therapy of hypertension. If the fixed combination represents the dose titrated to the individual patient’s needs, therapy with the fixed combination may be more convenient than with the separate components. Metoprolol tartrate and hydrochlorothiazide tablets are contraindicated in patients with: - Cardiogenic shock or decompensated heart failure. - Sinus bradycardia, sick sinus syndrome, and greater than first-degree block unless a permanent pacemaker is in place. - Anuria - Hypersensitivity to metoprolol tartrate or hydrochlorothiazide or to other sulfonamide derived drugs. Risk Summary Untreated hypertension during pregnancy can lead to adverse outcomes for the mother and the fetus (see Clinical Considerations) . Available data from published observational studies have not demonstrated a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes with metoprolol use during pregnancy. However, there are inconsistent reports of intrauterine growth restriction, preterm birth, and perinatal mortality with maternal use of beta blockers, including metoprolol, during pregnancy (see Data). There have been rare reports of jaundice, thrombocytopenia, and electrolyte imbalances in infants exposed to thiazide medications during pregnancy. In animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages up to 24 times, on a mg/m2 basis, the daily dose of 200 mg in a 60-kg patient. The combination of metoprolol tartrate/hydrochlorothiazide administered to rats from mid-late gestation through lactation also produced increased post-implantation loss and decreased neonatal survival (see Data) . 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 to 4% and 15 to 20%, respectively. Clinical consideration 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 Metoprolol Metoprolol crosses the placenta. Neonates born to mothers who are receiving metoprolol during pregnancy, may be at risk for hypotension, hypoglycemia, bradycardia, and respiratory depression. Observe neonates for symptoms of hypotension, bradycardia, hypoglycemia and respiratory depression and manage accordingly.     Data   Human Data Data from published observational studies did not demonstrate an association of major congenital malformations and use of either metoprolol or hydrochlorothiazide in pregnancy. The published literature has reported inconsistent findings of intrauterine growth retardation, preterm birth and perinatal mortality with maternal use of metoprolol during pregnancy; however, these studies have methodological limitations hindering interpretation. Methodological limitations include retrospective design, concomitant use of other medications, and other unadjusted confounders that may account for the study findings including the underlying disease in the mother. These observational studies cannot definitely establish or exclude any drug-associated risk during pregnancy. Animal Data Oral administration of metoprolol tartrate/hydrochlorothiazide combinations to pregnant rats during organogenesis at doses up to 200/50 mg/kg/day (10 and 20 times the MRHD on a mg/m2 basis for metoprolol and hydrochlorothiazide, respectively) or to pregnant rabbits at doses up to 25/6.25 mg/kg/day (about 2.5 and 5 times the MRHD on a mg/m2 basis for metoprolol and hydrochlorothiazide, respectively) produced no teratogenic effects. A 200/50 mg/kg/day metoprolol tartrate/hydrochlorothiazide combination administered to rats from mid-late gestation through lactation produced increased post-implantation loss and decreased neonatal survival. Metoprolol Metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at doses up to 24 times, on a mg/m2 basis, the daily dose of 200 mg in a 60-kg patient. Distribution studies in mice confirm exposure of the fetus when metoprolol tartrate is administered to the pregnant animal. These studies have revealed no evidence of impaired fertility or teratogenicity. Hydrochlorothiazide Hydrochlorothiazide administered to pregnant mice and rats during organogenesis at doses up to 3000 and 1000 mg/kg/day (600 and 400 times the MRHD on a mg/m2 basis), respectively, produced no harm to the fetus. Thiazides cross the placental barrier and appear in the cord blood. Risk Summary There are no data on the presence of metoprolol tartrate and hydrochlorothiazide in human milk, the effects on the breastfed infant, or the effects on milk production. However, data are available on the individual components of metoprolol tartrate and hydrochlorothiazide. Available data from published literature on metoprolol and hydrochlorothiazide report that each drug is present in human milk (see Data) . There are no reports of adverse effects on breastfed infants exposed to metoprolol or hydrochlorothiazide during lactation. Doses of hydrochlorothiazide associated with clinically significant diuresis have been associated with impaired milk production. There is no information regarding the effects of metoprolol on milk production. Monitor infants exposed to metoprolol tartrate and hydrochlorothiazide though breastmilk for drowsiness or poor feeding (see Clinical Considerations).   The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for metoprolol tartrate and hydrochlorothiazide and any potential adverse effects on the breastfed child from metoprolol tartrate and hydrochlorothiazide or from the underlying maternal condition. Clinical Considerations Monitor the breastfed infant for bradycardia or somnolence. Data Metoprolol Based on published case reports, the estimated daily infant dose of metoprolol received from breastmilk ranged from 0.05 mg to less than 1 mg. The estimated relative infant dosage was 0.5% to 2% of the mother’s weight-adjusted dosage. In two women who were taking unspecified amount of metoprolol, milk samples were taken after one dose of metoprolol. The estimated amount of metoprolol and alpha-hydroxymetoprolol in breast milk is reported to be less than 2% of the mother's weight-adjusted dosage. In a small study, breast milk was collected every 2 to 3 hours over one dosage interval, in three mothers (at least 3 months postpartum) who took metoprolol of unspecified amount. The average amount of metoprolol present in breast milk was 71.5 mcg/day (range 17 to 158.7). The average relative infant dosage was 0.5% of the mother's weight-adjusted dosage. Hydrochlorothiazide A single study involving one woman and her infant showed a peak concentration of 275 mcg/L at 3 hours following 50 mg dose. No drug was detected (< 20 mcg/L) in the infant’s plasma at 2-and 11-hours following mother’s dose. Infertility   Males Based on the published literature, beta blockers (including metoprolol) may cause erectile dysfunction and inhibit sperm motility. No evidence of impaired fertility due to metoprolol or hydrochlorothiazide was observed in rats [see Nonclinical Toxicology (13.1)]. Safety and effectiveness in pediatric patients have not been established. Clinical studies of metoprolol tartrate and hydrochlorothiazide 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. Hydrochlorothiazide is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Warnings and Precautions (5.8)]. 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 concomitant disease or other drug therapy.

Přehled produktů:

Metoprolol tartrate and hydrochlorothiazide Tablets, USP are available containing 50 mg/25 mg, 100 mg/25 mg or 100 mg/50 mg of metoprolol tartrate, USP and hydrochlorothiazide, USP. 50 mg/25 mg tablets are white to off-white colored, round shaped, biconvex, bevel edged scored uncoated tablet debossed with “L” on one side of score line and “230” on another side of score line and plain on other side. NDC 62332-115-30                bottle of 30 tablets NDC 62332-115-31                bottles of 100 tablets NDC 62332-115-91                bottles of 1000 tablets 100 mg/25 mg tablets are white to off-white colored, oval shaped, biconvex, bevel edged scored uncoated tablet debossed with “L” on one side of score line and “232” on another side of score line and plain on other side. NDC 62332-116-30                bottle of 30 tablets NDC 62332-116-31                bottle of 100 tablets NDC 62332-116-71                bottle of 500 tablets 100 mg/50 mg tablets are white to off-white colored, capsule shaped, biconvex, bevel edged scored uncoated tablet debossed with “L” on one side of score line and “231” on another side of score line and plain on other side. NDC 62332-117-30                bottle of 30 tablets NDC 62332-117-31                bottle of 100 tablets NDC 62332-117-71                bottle of 500 tablets Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in tight, light-resistant container (USP).

Stav Autorizace:

Abbreviated New Drug Application

Charakteristika produktu

METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE - METOPROLOL TARTRATE
AND HYDROCHLOROTHIAZIDE TABLET
ALEMBIC PHARMACEUTICALS INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
METOPROLOL TARTRATE
AND HYDROCHLOROTHIAZIDE TABLETS SAFELY AND EFFECTIVELY. SEE FULL
PRESCRIBING
INFORMATION FOR METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE TABLETS
METOPROLOL TARTRATE AND HYDROCHLOROTHIAZIDE TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 1984
INDICATIONS AND USAGE
Metoprolol tartrate and hydrochlorothiazide tablet is the combination
tablet of metoprolol tartrate, a beta
adrenoceptor blocker and hydrochlorothiazide (HCTZ), a thiazide
diuretic, indicated for the treatment of
hypertension, to lower blood pressure. (1)
Lowering blood pressure reduces the risk of fatal and nonfatal
cardiovascular events, primarily strokes and
myocardial infarctions. (1) (1)
DOSAGE AND ADMINISTRATION
Usual dose range: Hydrochlorothiazide 12.5 to 25 mg and metoprolol
tartrate 100 mg dosed once
daily. (2.1)
DOSAGE FORMS AND STRENGTHS
Tablets (metoprolol tartrate/hydrochlorothiazide): 50/25mg; 100/25mg;
100/50mg (3) (3)
CONTRAINDICATIONS
Hypersensitivity to metoprolol tartrate or hydrochlorothiazide or
other sulfonamide-derived drugs. (4)
Cardiogenic shock or decompensated heart failure. (4)
Sinus bradycardia, sick sinus syndrome, and greater than first-degree
block unless a permanent
pacemaker is in place. (4)
Anuria. (4)
WARNINGS AND PRECAUTIONS
• Abrupt cessation may exacerbate myocardial ischemia. (5.1)
• May worsen congestive heart failure. (5.2)
• Bronchospasm: Avoid beta-blockers. (5.3)
• Bradycardia. (5.4)
• Avoid discontinuing therapy prior to major surgery. (5.5)
• Diabetes: May mask symptoms of hypoglycemia and alter glucose
levels; monitor. (5.6).
• Monitor serum electrolytes and creatinine periodically. (5.7)
• Peripheral vascular disease: Can aggravate symptoms of arterial
insufficiency. (5.9)
• Pheochromocytoma: First initiate therapy with an alpha block