Metoprolol Tartrate

1 INDICATIONS AND USAGE Metoprolol tartrate tablets are a beta-adrenergic blocker indicated for the treatment of: • Hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. ( 1.1 ) • Angina Pectoris. ( 1.2 ) • Myocardial Infarction, to reduce the risk of cardiovascular mortality when used in conjunction with intravenous metoprolol therapy in patients with definite or suspected acute myocardial infarction in hemodynamically stable patients. ( 1.3 ) 1.1 Hypertension Metoprolol tartrate tablets are indicated for the treatment of hypertension in adult patients, 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 tablets may be administered with other antihypertensive agents. 1.2 Angina Pectoris Metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris, to reduce angina attacks and to improve exercise tolerance. 1.3 Myocardial Infarction Metoprolol tartrate tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used alone or in conjunction with intravenous metoprolol.

DOSAGE AND ADMINISTRATION Hypertension Individualize the dosage of metoprolol tartrate tablets. Metoprolol tartrate tablets should be taken with or immediately following meals. The usual initial dosage of metoprolol tartrate tablets is 100 mg daily in single or divided doses, whether used alone or added to a diuretic. Increase the dosage at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after one week of therapy. The effective dosage range of metoprolol tartrate tablets is 100 mg per day to 450 mg per day. Dosages above 450 mg per day have not been studied. While once daily dosing is effective and can maintain a reduction in blood pressure throughout the day, lower doses (especially 100 mg) may not maintain a full effect at the end of the 24-hour period, and larger or more frequent daily doses may be required. This can be evaluated by measuring blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. Beta 1 selectivity diminishes as the dose of Metoprolol is increased. Angina Pectoris The dosage of metoprolol tartrate tablets should be individualized. Metoprolol tartrate tablets should be taken with or immediately following meals. The usual initial dosage of metoprolol tartrate tablets is 100 mg daily, given in two divided doses. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is pronounced slowing of the heart rate. The effective dosage range of metoprolol tartrate tablets is 100 mg per day to 450 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, gradually decrease the dosage over a period of 1 to 2 weeks (see WARNINGS ). Myocardial Infarction Early Treatment During the early phase of definite or suspected acute myocardial infarction, initiate treatment with metoprolol tartrate tablets as soon as possible after the patient’s arrival in the hospital. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized. Begin treatment in this early phase with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate each; give the injections at approximately 2 minute intervals. During the intravenous administration of metoprolol, monitor blood pressure, heart rate, and electrocardiogram. In patients who tolerate the full intravenous dose (15 mg), initiate metoprolol tartrate tablets, 50 mg every 6 hours, 15 minutes after the last intravenous dose and continue for 48 hours. Thereafter, the maintenance dosage is 100 mg twice daily (see Late Treatment below). Start patients who appear not to tolerate the full intravenous dose on metoprolol tartrate tablets either 25 mg or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last intravenous dose or as soon as their clinical condition allows. In patients with severe intolerance, discontinue metoprolol tartrate tablets (see WARNINGS ). Late Treatment Start patients with contraindications to treatment during the early phase of suspected or definite myocardial infarction, patients who appear not to tolerate the full early treatment, and patients in whom the physician wishes to delay therapy for any other reason on metoprolol tartrate tablets, 100 mg twice daily, as soon as their clinical condition allows. Continue therapy for at least 3 months. Although the efficacy of metoprolol beyond 3 months has not been conclusively established, data from studies with other beta-blockers suggest that treatment should be continued for 1 to 3 years. Special Populations Pediatric Patients No pediatric studies have been performed. The safety and efficacy of metoprolol in pediatric patients have not been established. Renal Impairment No dose adjustment of metoprolol tartrate tablets i …

3 DOSAGE FORMS AND STRENGTHS Metoprolol Tartrate Tablets, USP are available containing 25 mg, 37.5 mg, 50 mg, 75 mg or 100 mg of metoprolol tartrate, USP. • The 25 mg tablets are white, film-coated, round, scored tablets debossed with M over 18 on one side of the tablet and scored on the other side. • The 37.5 mg tablets are light blue, film-coated, round, scored tablets debossed with M above the score and MT below the score on one side of the tablet and 37.5 on the other side. • The 50 mg tablets are pink, film-coated, round, scored tablets debossed with M over 32 on one side of the tablet and scored on the other side. • The 75 mg tablets are white, film-coated, round, scored tablets debossed with M above the score and MT below the score on one side of the tablet and 75 on the other side. • The 100 mg tablets are light blue, film-coated, round, scored tablets debossed with M over 47 on one side of the tablet and scored on the other side. • Metoprolol Tartrate Tablets: 25 mg, 37.5 mg, 50 mg, 75 mg and 100 mg. ( 3 )

CONTRAINDICATIONS Hypertension and Angina Metoprolol tartrate tablets are contraindicated in sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure (see WARNINGS ). Hypersensitivity to metoprolol and related derivatives, or to any of the excipients; hypersensitivity to other beta-blockers (cross sensitivity between beta-blockers can occur). Sick-sinus Syndrome. Severe peripheral arterial circulatory disorders. Myocardial Infarction Metoprolol tartrate tablets are contraindicated in patients with a heart rate < 45 beats/min; second- and third-degree heart block; significant first-degree heart block (P-R interval ≥ 0.24 sec); systolic blood pressure < 100 mmHg; or moderate-to-severe cardiac failure (see WARNINGS ).

ADVERSE REACTIONS Hypertension and Angina Most adverse effects have been mild and transient. Central Nervous System Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported. Cardiovascular Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; and hypotension have been reported in about 1 of 100 patients. Gangrene in patients with preexisting severe peripheral circulatory disorders has also been reported very rarely (see CONTRAINDICATIONS , WARNINGS , and PRECAUTIONS ). Respiratory Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients (see WARNINGS ). Rhinitis has also been reported. Gastrointestinal Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1 of 100 patients. Vomiting was a common occurrence. Post-marketing experience reveals very rare reports of hepatitis, jaundice and nonspecific hepatic dysfunction. Isolated cases of transaminase, alkaline phosphatase, and lactic dehydrogenase elevations have also been reported. Hypersensitive Reactions Pruritus or rash have occurred in about 5 of 100 patients. Very rarely, photosensitivity and worsening of psoriasis have been reported. Miscellaneous Peyronie’s disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, and tinnitus have also been reported. There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. There have been very rare reports of weight gain, arthritis, and retroperitoneal fibrosis (relationship to metoprolol has not been definitely established). The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with metoprolol. Myocardial Infarction Central Nervous System Tiredness has been reported in about 1 of 100 patients. Vertigo, sleep disturbances, hallucinations, headache, dizziness, visual disturbances, confusion, and reduced libido have also been reported, but a drug relationship is not clear. Cardiovascular In the randomized comparison of metoprolol and placebo described in the CLINICAL PHARMACOLOGY section, the following adverse reactions were reported: Metoprolol Tartrate Tablets Placebo Hypotension (systolic BP < 90 mmHg) 27.4% 23.2% Bradycardia (heart rate < 40 beats/min) 15.9% 6.7% Second- or third-degree heart block 4.7% 4.7% First-degree heart block (P-R ≥ 0.26 sec) 5.3% 1.9% Heart failure 27.5% 29.6% Respiratory Dyspnea of pulmonary origin has been reported in fewer than 1 of 100 patients. Gastrointestinal Nausea and abdominal pain have been reported in fewer than 1 of 100 patients. Dermatologic Rash and worsened psoriasis have been reported, but a drug relationship is not clear. Miscellaneous Unstable diabetes and claudication have been reported, but a drug relationship is not clear. Potential Adverse Reactions A variety of adverse reactions not listed above have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to metoprolol. Central Nervous System Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics. Cardiovascular Intensification of AV block (see CONTRAINDICATIONS ). Hematologic Agranulocytosis, nonthrombocytopenic purpura and thrombocytopenic purpura. Hypersensitive Reactions Fever combined with aching and sore throa …

Drug Interactions Catecholamine-Depleting Drugs Catecholamine-depleting drugs (e.g., reserpine) may have an additive effect when given with beta-blocking agents or monoamine oxidase (MAO) inhibitors. Observe patients treated with metoprolol plus a catecholamine depletor for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension. In addition, possibly significant hypertension may theoretically occur up to 14 days following discontinuation of the concomitant administration with an irreversible MAO inhibitor. Digitalis Glycosides and Beta-Blockers Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. Monitor heart rate and PR interval. Calcium Channel Blockers Concomitant administration of a beta-adrenergic antagonist with a calcium channel blocker may produce an additive reduction in myocardial contractility because of negative chronotropic and inotropic effects. CYP2D6 Inhibitors Potent inhibitors of the CYP2D6 enzyme may increase the plasma concentration of metoprolol which would mimic the pharmacokinetics of CYP2D6 poor metabolizer (see CLINICAL PHARMACOLOGY: Pharmacokinetics ). Increase in plasma concentrations of metoprolol would decrease the cardioselectivity of metoprolol. Known clinically significant potent inhibitors of CYP2D6 are antidepressants such as fluvoxamine, fluoxetine, paroxetine, sertraline, bupropion, clomipramine and desipramine; antipsychotics such as chlorpromazine, fluphenazine, haloperidol and thioridazine; antiarrhythmics such as quinidine or propafenone; antiretrovirals such as ritonavir; antihistamines such as diphenhydramine; antimalarials such as hydroxychloroquine or quinidine; antifungals such as terbinafine. Hydralazine Concomitant administration of hydralazine may inhibit presystemic metabolism of metoprolol leading to increased concentrations of metoprolol. Alpha-Adrenergic Agents Antihypertensive effect of alpha-adrenergic blockers such as guanethidine, betanidine, reserpine, alpha-methyldopa or clonidine may be potentiated by beta-blockers including metoprolol. Beta- adrenergic blockers may also potentiate the postural hypotensive effect of the first dose of prazosin, probably by preventing reflex tachycardia. On the contrary, beta-adrenergic blockers may also potentiate the hypertensive response to withdrawal of clonidine in patients receiving concomitant clonidine and beta-adrenergic blocker. If a patient is treated with clonidine and metoprolol concurrently, and clonidine treatment is to be discontinued, stop metoprolol several days before clonidine is withdrawn. Rebound hypertension that can follow withdrawal of clonidine may be increased in patients receiving concurrent beta-blocker treatment. Ergot Alkaloid Concomitant administration with beta-blockers may enhance the vasoconstrictive action of ergot alkaloids. Dipyridamole In general, administration of a beta-blocker should be withheld before dipyridamole testing, with careful monitoring of heart rate following the dipyridamole injection. Carcinogenesis, Mutagenesis, Impairment of Fertility 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, 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, 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, …

8 USE IN SPECIFIC POPULATIONS Hepatic Impairment: Consider initiating metoprolol tartrate tablet therapy at low doses and gradually increase dosage to optimize therapy, while monitoring closely for adverse events. ( 8.6 ) 8.1 Pregnancy Risk Summary Available data from published observational studies have not demonstrated an association of adverse developmental outcomes with maternal use of metoprolol during pregnancy (see Data ) . Untreated hypertension and myocardial infarction during pregnancy can lead to adverse outcomes for the mother and the fetus (see Error! Hyperlink reference not valid. ) . In animal reproduction studies, metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, approximately 11 times the daily dose of 450 mg in a 60-kg patient on a mg/m 2 basis. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 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 and manage accordingly. Data Human Data Data from published observational studies did not demonstrate an association of major congenital malformations and use of metoprolol 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 Metoprolol has been shown to increase post-implantation loss and decrease neonatal survival in rats at oral dosages of 500 mg/kg/day, i.e., 11 times, on a mg/m 2 basis, the daily dose of 450 mg in a 60-kg patient. No fetal abnormalities were observed when pregnant rats received metoprolol orally up to a dose of 200 mg/kg/day, i.e., 4 times, the daily dose of 400mg in a 60-kg patient. 8.2 Lactation Risk Summary Limited available data from published literature report that metoprolol is present in human milk. The estimated daily infant dose of metoprolol received from breastmilk ranges 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 (see Data ) . No adverse reactions of metoprolol on the breastfed infant have been identified. There is no information regarding the effects of metoprolol on milk production. Clinical Consideration Monitoring for adverse reactions For a lactating woman who is a slow metabolizer of metoprolol, monitor the breastfed infant for bradycardia and other symptoms of beta-blockade such as dry mouth, skin or eyes, diarrhea or constipation. In a report of 6 mothers taking metoprolol, none reported adverse effects in her breastfed infant. Data Limited publish …

12.1 Mechanism of Action Metoprolol is a beta 1 -selective (cardioselective) adrenergic receptor blocking agent. This preferential effect is not absolute, however, and at higher plasma concentrations, metoprolol also inhibits beta 2 -adrenoreceptors, chiefly located in the bronchial and vascular musculature. Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at plasma concentrations much greater than required for beta-blockade. Animal and human experiments indicate that metoprolol slows the sinus rate and decreases AV nodal conduction. The relative beta 1 -selectivity of metoprolol has been confirmed by the following: (1) In normal subjects, metoprolol is unable to reverse the beta 2 -mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective beta-blockers, which completely reverse the vasodilating effects of epinephrine. (2) In asthmatic patients, metoprolol reduces FEV 1 and FVC significantly less than a nonselective beta-blocker, propranolol, at equivalent beta 1 -receptor blocking doses. Hypertension: The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated. However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity. Angina Pectoris: By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, metoprolol reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris. Heart Failure: The precise mechanism for the beneficial effects of beta-blockers in heart failure has not been elucidated.

11 DESCRIPTION Metoprolol tartrate tablets, USP contain metoprolol tartrate, a selective beta 1 -adrenoreceptor blocking agent. Metoprolol tartrate 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 with a molecular weight of 684.82. It is very soluble in water; freely soluble in methylene chloride, in chloroform, and in alcohol; slightly soluble in acetone; and insoluble in ether. Metoprolol tartrate tablets, USP are available as 25 mg, 37.5 mg, 50 mg, 75 mg or 100 mg tablets for oral administration containing 25 mg, 37.5 mg, 50 mg, 75 mg or 100 mg metoprolol tartrate, respectively. Inactive Ingredients: anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, povidone, sodium lauryl sulfate, titanium dioxide and triacetin. The 37.5 mg tablets also contain FD&C Blue No. 2 Aluminum Lake. The 50 mg tablets also contain FD&C Blue No. 2 Aluminum Lake, D&C Red No. 27 Aluminum Lake and FD&C Red No. 40 Aluminum Lake. The 100 mg tablets also contain FD&C Blue No. 2 Aluminum Lake. Metoprolol Tartrate Structural Formula

10 OVERDOSAGE Signs and Symptoms – Overdosage of metoprolol tartrate tablets may lead to severe bradycardia, hypotension, and cardiogenic shock. Clinical presentation can also include: atrioventricular block, heart failure, bronchospasm, hypoxia, impairment of consciousness/coma, nausea and vomiting. Treatment – Consider treating the patient with intensive care. Patients with myocardial infarction or heart failure may be prone to significant hemodynamic instability. Beta-blocker overdose may result in significant resistance to resuscitation with adrenergic agents, including beta-agonists. On the basis of the pharmacologic actions of metoprolol, employ the following measures. Hemodialysis is unlikely to make a useful contribution to metoprolol elimination [see Clinical Pharmacology (12.3) ] . Bradycardia: Evaluate the need for atropine, adrenergic-stimulating drugs or pacemaker to treat bradycardia and conduction disorders. Hypotension: Treat underlying bradycardia. Consider intravenous vasopressor infusion, such as dopamine or norepinephrine. Heart failure and shock: May be treated when appropriate with suitable volume expansion, injection of glucagon (if necessary, followed by an intravenous infusion of glucagon), intravenous administration of adrenergic drugs such as dobutamine, with α1 receptor agonistic drugs added in presence of vasodilation. Bronchospasm: Can usually be reversed by bronchodilators.

16 HOW SUPPLIED/STORAGE AND HANDLING Metoprolol Tartrate Tablets, USP are available as follows: Tablets 25 mg are white round shaped, film coated tablets debossed with ‘C over 73’ on one side and deep break line on other side. Bottles of 20 NDC 76420-054-20 (repackaged from NDC 57237-100-xx) Bottles of 30 NDC 76420-054-30 (repackaged from NDC 57237-100-xx) Bottles of 60 NDC 76420-054-60 (repackaged from NDC 57237-100-xx) Bottles of 90 NDC 76420-054-90 (repackaged from NDC 57237-100-xx) Bottles of 100 NDC 76420-054-01 (relabeled from NDC 57237-100-01) Bottles of 1,000 NDC 76420-054-00 (relabeled from NDC 57237-100-99) Tablets 50 mg are pink round shaped, film coated tablets debossed with ‘C over 74’ on one side and deep break line on other side. Bottles of 20 NDC 76420-953-20 (repackaged from NDC 57237-101-xx) Bottles of 30 NDC 76420-953-30 (repackaged from NDC 57237-101-xx) Bottles of 60 NDC 76420-953-60 (repackaged from NDC 57237-101-xx) Bottles of 90 NDC 76420-953-90 (repackaged from NDC 57237-101-xx) Bottles of 100 NDC 76420-953-01 (relabeled from NDC 57237-101-01) Bottles of 1,000 NDC 76420-953-00 (relabeled from NDC 57237-101-99) Tablets 100 mg are light blue round shaped, film coated tablets debossed with ‘C over 75’ on one side and deep break line on other side. Bottles of 20 NDC 76420-954-20 (repackaged from NDC 57237-102-xx) Bottles of 30 NDC 76420-954-30 (repackaged from NDC 57237-102-xx) Bottles of 60 NDC 76420-954-60 (repackaged from NDC 57237-102-xx) Bottles of 90 NDC 76420-954-90 (repackaged from NDC 57237-102-xx) Bottles of 100 NDC 76420-954-01 (relabeled from NDC 57237-102-01) Bottles of 1,000 NDC 76420-954-00 (relabeled from NDC 57237-102-99) Store at 20° to 25 °C (68° to 77 °F); excursions permitted to 15 ° to 30 °C (59 ° to 86 °F) [see USP Controlled Room Temperature ]. Protect from moisture and heat. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.