FDA Label for Metoprolol Tartrate

Warnings

Heart Failure
Beta blockers, like Metoprolol Tartrate Tablets USP, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. If signs or symptoms of heart failure develop, treat the patient according to recommended guidelines. It may be necessary to lower the dose of Metoprolol Tartrate Tablets USP or to discontinue it.

Use During Major Surgery
Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.

Bradycardia
Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of Metoprolol Tartrate Tablets USP. Patients with first-degree atrioventricular block, sinus node dysfunction or conduction disorders may be at increased risk. Monitor heart rate and rhythm in patients receiving Metoprolol Tartrate Tablets USP. If severe bradycardia develops, reduce or stop Metoprolol Tartrate Tablets USP.

Exacerbation of Bronchospastic Disease
Patients with bronchospastic disease, should, in general, not receive beta-blockers, including Metoprolol Tartrate Tablets USP. Because of its relative beta₁ selectivity, however, Metoprolol Tartrate Tablets USP may be used in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Because beta₁ selectivity is not absolute use the lowest possible dose of Metoprolol Tartrate Tablets USP and consider administering Metoprolol Tartrate Tablets USP in smaller doses 3 times daily, instead of larger doses two times daily, to avoid the higher plasma levels associated with the longer dosing interval (see DOSAGE AND ADMINISTRATION). Bronchodilators, including beta₂ agonists, should be readily available or administered concomitantly.

Diabetes and Hypoglycemia
Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected.

Pheochromocytoma
If Metoprolol Tartrate Tablets USP is used in the setting of pheochromocytoma, it should be given in combination with an alpha blocker, and only after the alpha blocker has been initiated. Administration of beta blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure due to the attenuation of beta-mediated vasodilatation in skeletal muscle.

Thyrotoxicosis
Metoprolol Tartrate Tablets USP may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Avoid abrupt withdrawal of beta-blockade, which might precipitate a thyroid storm.

Precautions

Risk of Anaphylactic Reactions
While taking beta blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.

Information for Patients
Advise patients to take Metoprolol Tartrate Tablets USP regularly and continuously, as directed, with or immediately following meals. If a dose should be missed, the patient should take only the next scheduled dose (without doubling it). Patients should not discontinue Metoprolol Tartrate Tablets USP without consulting the physician.

Advise patients (1) to avoid operating automobiles and machinery or engaging in other tasks requiring alertness until the patient’s response to therapy with Metoprolol Tartrate Tablets USP have been determined; (2) to contact the physician if any difficulty in breathing occurs; (3) to inform the physician or dentist before any type of surgery that he or she is taking Metoprolol Tartrate Tablets USP.

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 Tartrate Tablets USP 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 Tartrate Tablets USP which would mimic the pharmacokinetics of CYP2D6 poor metabolizer (see PHARMACOKINETICS section). 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 Tartrate Tablets USP. 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 Tartrate Tablets USP concurrently, and clonidine treatment is to be discontinued, stop Metoprolol Tartrate Tablets USP 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.

Pregnancy Category C

Upon confirming the diagnosis of pregnancy, women should immediately inform the doctor.

Metoprolol Tartrate Tablets USP has been shown to increase postimplantation loss and decrease neonatal survival in rats at doses up to 11 times the maximum daily human dose of 450 mg, when based on surface area. Distribution studies in mice confirm exposure of the fetus when Metoprolol Tartrate Tablets USP is administered to the pregnant animal. These limited animal studies do not indicate direct or indirect harmful effects with respect to teratogenicity (see CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY).

There are no adequate and well-controlled studies in pregnant women. The amount of data on the use of metoprolol in pregnant women is limited. The risk to the fetus/ mother is unknown. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Metoprolol Tartrate Tablets USP is excreted in breast milk in a very small quantity. An infant consuming 1 liter of breast milk daily would receive a dose of less than 1 mg of the drug.

Fertility

The effects of Metoprolol Tartrate Tablets USP on the fertility of human have not been studied.

Metoprolol Tartrate Tablets USP showed effects on spermatogenesis in male rats at a therapeutic dose level, but had no effect on rates of conception at higher doses in animal fertility studies (see CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY).

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical trials of Metoprolol Tartrate Tablets USP in hypertension did not include sufficient numbers of elderly patients to determine whether patients over 65 years of age differ from younger subjects in their response to Metoprolol Tartrate Tablets USP. Other reported clinical experience in elderly hypertensive patients has not identified any difference in response from younger patients.

In worldwide clinical trials of Metoprolol Tartrate Tablets USP in myocardial infarction, where approximately 478 patients were over 65 years of age (0 over 75 years of age), no age-related differences in safety and effectiveness were found. Other reported clinical experience in myocardial infarction has not identified differences in response between the elderly and younger patients. However, greater sensitivity of some elderly individuals taking Metoprolol Tartrate Tablets USP cannot be categorically ruled out. Therefore, in general, it is recommended that dosing proceed with caution in this population.

Hypertension And Angina

Most adverse effects have been mild and transient.

How Supplied

Metoprolol Tartrate Tablets, USP are available containing 25 mg, 50 mg or 100 mg of metoprolol tartrate USP.

The 25 mg tablets are white film-coated, round, scored tablets debossed with Y over 25 on one side of the tablet and scored on the other side. They are available as follows:

NDC 69445-004-04 bottles of 100 tablets

NDC 69445-004-03 bottles of 500 tablets

The 50 mg tablets are pink film-coated, round, scored tablets debossed with Y over 50 on one side of the tablet and scored on the other side. They are available as follows:

NDC 69445-005-04 bottles of 100 tablets

NDC 69445-005-05 bottles of 1,000 tablets

The 100 mg tablets are light blue film-coated, round, scored tablets debossed with Y over 100 on one side of the tablet and scored on the other side. They are available as follows:

NDC 69445-006-04 bottles of 100 tablets

NDC 69445-006-05 bottles of 1,000 tablets

Store at 20° to 25°C (68° to 77°F), excursions permitted to 15- 30°C (59- 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.

To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Manufactured by:
Yabao Pharmaceutical Co., Ltd.
Beijing 101111, China

For:
YoungTech Pharmaceuticals, Inc.
Cranbury, NJ 08512, USA

Rev: Nov 2019