Complete SPL Sections
1 INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
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.
2 DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
3 DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
Metoprolol tartrate and hydrochlorothiazide tablets, USP are supplied as capsule-shaped tablets in the following strengths: 50 mg/25 mg: Yellow, debossed with ‘S’ and ‘370’ on either side of breakline on one side and plain on other side 100 mg/25 mg: Pink, debossed with ‘S’ and ‘368’ on either side of breakline on one side and plain on other side 100 mg/50 mg: Yellow, debossed with ‘S’ and ‘369’ on either side of breakline on one side and plain on other side
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
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.
5 WARNINGS AND PRECAUTIONS
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
The following adverse reactions are described in more detail elsewhere in the label; • Worsening angina or myocardial infarction [see Warnings and Precautions (5)] • Worsening heart failure [see Warnings and Precautions (5)] • Worsening AV block [see Contraindications (4)]
7 DRUG INTERACTIONS
DRUG INTERACTIONS SECTION
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
10 OVERDOSAGE
OVERDOSAGE SECTION
11 DESCRIPTION
DESCRIPTION SECTION
Metoprolol tartrate and hydrochlorothiazide tablets, USP has the antihypertensive effect of metoprolol tartrate, a beta adrenoreceptor blocker, and hydrochlorothiazide, a thiazide diruetic. It is available as tablets for oral administration. The 50 mg/25 mg tablets contain 50 mg of metoprolol tartrate USP and 25 mg of hydrochlorothiazide USP; the 100 mg/25 mg tablets contain 100 mg of metoprolol tartrate USP and 25 mg of hydrochlorothiazide USP; and the 100 mg/50 mg tablets contain 100 mg of metoprolol tartrate USP and 50 mg of hydrochlorothiazide USP. Metoprolol tartrate USP is (±)-1- (Isopropylamino)-3-[ p -(2-methoxyethyl)phenoxy]-2-propanol L-(+)-tartrate (2:1) salt, and its structural formula is Metoprolol tartrate USP is a white, crystalline powder. It is very soluble in water; freely soluble in methylene chloride, in chloroform, and in alcohol; slightly soluble in acetone; and insoluble in ether. Its molecular weight is 684.82. Hydrochlorothiazide is 6-chloro-3, 4-dihydro-2 H -1,2,4-benzothiadiazine-7- sulfonamide 1,1- dioxide, and its structural formula is Hydrochlorothiazide USP is a white, or practically white, practically odorless, crystalline powder. It is freely soluble in sodium hydroxide solution, in n -butylamine, and in dimethylformamide; sparingly soluble in methanol; slightly soluble in water; and insoluble in ether, in chloroform, and in dilute mineral acids. Its molecular weight is 297.73. Inactive Ingredients: Microcrystalline cellulose, anhydrous lactose, lactose monohydrate, pregelatinized starch, corn starch, compressible sugar, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, D&C Yellow No. 10 (50 mg/25 mg and 100 mg/50 mg tablets), and FD&C Red No. 40 and FD&C Yellow No. 6 (100 mg/25 mg tablets).
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
Metoprolol tartrate and hydrochlorothiazide tablets: Carcinogenicity and mutagenicity studies have not been conducted with metoprolol tartrate and hydrochlorothiazide tablets. Metoprolol tartrate and hydrochlorothiazide tablets produced no evidence of impaired fertility in male or female rats administered gavaged doses up to 200/50 mg/kg (about 10 times and 20 times the maximum recommended human dose (MRHD) of metoprolol and hydrochlorothiazide, respectively, on a mg/m 2 basis) prior to mating and throughout gestation and rearing of young. Metoprolol tartrate: Long-term studies in animals have been conducted to evaluate carcinogenic potential. In a 2-year study in rats at three oral dosage levels of up to 800 mg/kg per day (41 times, on a mg/m 2 basis, the daily dose of 200 mg for a 60-kg patient), there was no increase in the development of spontaneously occurring benign or malignant neoplasms of any type. The only histologic changes that appeared to be drug related were an increased incidence of generally mild focal accumulation of foamy macrophages in pulmonary alveoli and a slight increase in biliary hyperplasia. In a 21-month study in Swiss albino mice at three oral dosage levels of up to 750 mg/kg per day (about 18 times, on a mg/m 2 basis, the daily dose of 200 mg for a 60-kg patient), benign lung tumors (small adenomas) occurred more frequently in female mice receiving the highest dose than in untreated control animals. There was no increase in malignant or total (benign plus malignant) lung tumors, or in the overall incidence of tumors or malignant tumors. This 21-month study was repeated in CD-1 mice, and no statistically or biologically significant differences were observed between treated and control mice of either sex for any type of tumor. All mutagenicity tests performed (a dominant lethal study in mice, chromosome studies in somatic cells, a Salmonella/mammalian-microsome mutagenicity test, and a nucleus anomaly test in somatic interphase nuclei) were negative. No evidence of impaired fertility due to metoprolol tartrate was observed in a study performed in rats at doses up to 22 times, on a mg/m 2 basis, the daily dose of 200 mg in a 60 kg patient. Hydrochlorothiazide : Two-year feeding studies in mice and rats uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice at doses up to approximately 600 mg/kg/day (about 120 times the MRHD of 25 mg/day on a mg/m 2 basis) or in male and female rats at doses up to approximately 100 mg/kg/day (about 40 times the MRHD on a mg/m 2 basis). However, there was equivocal evidence for hepatocarcinogenicity in male mice. Hydrochlorothiazide was not genotoxic in the Ames bacterial mutagenicity testor the Chinese Hamster Ovary (CHO) test for chromosomal aberrations. Nor was it genotoxic in vivo assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, and in the Aspergillus nidulans nondisjunction assay at an unspecified concentration. Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 mg/kg/day and 4 mg/kg/day (about 20 times and 1.6 times the MRHD, on a mg/m 2 basis), respectively, prior to mating and throughout gestation.
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
Tablets 50 mg/25 mg Capsule-shaped, yellow, debossed with ‘S’ and ‘370’ on either side of breakline on one side and plain on other side, 50 mg of metoprolol tartrate and 25 mg of hydrochlorothiazide Bottles of 30 with Child Resistant Cap……………NDC 62756-370-83 Bottles of 100 with Child Resistant Cap…………..NDC 62756-370-88 Bottles of 100 ……..NDC 62756-370-08 Bottles of 1000 …....NDC 62756-370-18 Tablets 100 mg/25 mg Capsule-shaped, pink, debossed with ‘S’ and ‘368’ on either side of breakline on one side and plain on other side, 100 mg of metoprolol tartrate and 25 mg of hydrochlorothiazide Bottles of 30 with Child Resistant Cap……………NDC 62756-368-83 Bottles of 100 with Child Resistant Cap…………..NDC 62756-368-88 Bottles of 100 ……..NDC 62756-368-08 Bottles of 1000 …....NDC 62756-368-18 Tablets 100 mg/50 mg Capsule-shaped, yellow, debossed with ‘S’ and ‘369’ on either side of breakline on one side and plain on other side, 100 mg of metoprolol tartrate and 50 mg of hydrochlorothiazide Bottles of 30 with Child Resistant Cap……………NDC 62756-369-83 Bottles of 100 with Child Resistant Cap…………..NDC 62756-369-88 Bottles of 100 ……..NDC 62756-369-08 Bottles of 1000 …....NDC 62756-369-18 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature]. Protect from moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Inform patients or caregivers that there is a risk of hypoglycemia when metoprolol tartrate and hydrochlorothiazide tablets is given to patients who are fasting or who are vomiting. Instruct patients or caregivers how to monitor for signs of hypoglycemia [see Warnings and Precautions (5.6)]. Advise patients to take metoprolol tartrate and hydrochlorothiazide tablets as directed, with or immediately following meals. If a dose is missed, advise the patient to take only the next scheduled dose (without doubling it). Advise patients to not discontinue metoprolol tartrate and hydrochlorothiazide tablets without consulting their healthcare provider. Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 Manufactured by: Sun Pharmaceutical Industries Limited Survey No. 1012, Dadra-396 193, U.T. of D & NH and Daman & Diu, India. Revised. 01/2024
PRINCIPAL DISPLAY PANEL- Label - 50 mg-25 mg
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 62756-370-88 Metoprolol Tartrate and Hydrochlorothiazide Tablets, USP 50 mg/25 mg Rx only 100 TABLETS SUN PHARMA
PRINCIPAL DISPLAY PANEL-Label - 100 mg-25 mg
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 62756-368-88 Metoprolol Tartrate and Hydrochlorothiazide Tablets, USP 100 mg/25 mg Rx only 100 TABLETS SUN PHARMA
PRINCIPAL DISPLAY PANEL-Label - 100 mg-50 mg
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 62756-369-88 Metoprolol Tartrate and Hydrochlorothiazide Tablets, USP 100 mg/50 mg Rx only 100 TABLETS SUN PHARMA