Cardiovascular: Cold extremities, arterial insufficiency usually of the Raynaud type , palpitations, peripheral edema, syncope, chest pain and hypotension. Gastrointestinal: Nausea, dry mouth, constipation, flatulence, heartburn, hepatitis, vomiting.
Potential Adverse Reactions: In addition, there are adverse reactions not listed above that have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to TOPROL-XL.
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, clouded sensorium, and decreased performance on neuropsychometrics.
Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura. Clinical laboratory findings may include elevated levels of serum transaminase, alkaline phosphatase, and lactate dehydrogenase.
Catecholamine depleting drugs e. Observe patients treated with TOPROL-XL plus a catecholamine depletor for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.
Drugs that inhibit CYP2D6 such as quinidine, fluoxetine, paroxetine, and propafenone are likely to increase metoprolol concentration. In healthy subjects with CYP2D6 extensive metabolizer phenotype, coadministration of quinidine mg and immediate-release metoprolol mg tripled the concentration of S-metoprolol and doubled the metoprolol elimination half-life. In four patients with cardiovascular disease, coadministration of propafenone mg t.
These increases in plasma concentration would decrease the cardioselectivity of metoprolol. Digitalis glycosides, clonidine, diltiazem and verapamil slow atrioventricular conduction and decrease heart rate. Concomitant use with beta blockers can increase the risk of bradycardia. If clonidine and a beta blocker, such as metoprolol are coadministered, withdraw the beta-blocker several days before the gradual withdrawal of clonidine because beta-blockers may exacerbate the rebound hypertension that can follow the withdrawal of clonidine.
If replacing clonidine by beta-blocker therapy, delay the introduction of beta-blockers for several days after clonidine administration has stopped [see Warnings and Precautions 5. 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. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, use this drug during pregnancy only if clearly needed.
Metoprolol is excreted in breast milk in very small quantities. An infant consuming 1 liter of breast milk daily would receive a dose of less than 1 mg of the drug. The study did not meet its primary endpoint dose response for reduction in SBP. Some pre-specified secondary endpoints demonstrated effectiveness including:. Mean reduction in heart rate ranged from 5 to 7 bpm but considerably greater reductions were seen in some individuals [see Dosage and Administration 2.
No clinically relevant differences in the adverse event profile were observed for pediatric patients aged 6 to 16 years as compared with adult patients. Clinical studies of TOPROL-XL in hypertension did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Other reported clinical experience in hypertensive patients has not identified differences in responses between elderly and younger patients. There were no notable differences in efficacy or the rate of adverse reactions between older and younger patients. In general, use a low initial starting dose in elderly patients given their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Therefore, initiate therapy at doses lower than those recommended for a given indication; and increase doses gradually in patients with impaired hepatic function. The systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. No reduction in dosage is needed in patients with chronic renal failure [see Clinical Pharmacology Treatment — Consider treating the patient with intensive care.
Patients with myocardial infarction or heart failure may be prone to significant hemodynamic instability. Seek consultation with a regional poison control center and a medical toxicologist as needed.
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. There is very limited experience with the use of hemodialysis to remove metoprolol, however metoprolol is not highly protein bound. 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. TOPROL-XL, metoprolol succinate, is a beta 1 -selective cardioselective adrenoceptor blocking agent, for oral administration, available as extended-release tablets.
The tablets comprise a multiple unit system containing metoprolol succinate in a multitude of controlled release pellets. Each pellet acts as a separate drug delivery unit and is designed to deliver metoprolol continuously over the dosage interval.
The tablets contain Its structural formula is:. Metoprolol succinate is a white crystalline powder with a molecular weight of It is freely soluble in water; soluble in methanol; sparingly soluble in ethanol; slightly soluble in dichloromethane and 2-propanol; practically insoluble in ethyl-acetate, acetone, diethylether and heptane.
Inactive ingredients: silicon dioxide, cellulose compounds, sodium stearyl fumarate, polyethylene glycol, titanium dioxide, paraffin.
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.
Heart Failure: The precise mechanism for the beneficial effects of beta-blockers in heart failure has not been elucidated. Clinical pharmacology studies have confirmed the beta-blocking activity of metoprolol in man, as shown by 1 reduction in heart rate and cardiac output at rest and upon exercise, 2 reduction of systolic blood pressure upon exercise, 3 inhibition of isoproterenol-induced tachycardia, and 4 reduction of reflex orthostatic tachycardia. 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. The relationship between plasma metoprolol levels and reduction in exercise heart rate is independent of the pharmaceutical formulation.
Although beta-adrenergic receptor blockade is useful in the treatment of angina, hypertension, and heart failure there are situations in which sympathetic stimulation is vital. In patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive.
In the presence of AV block, beta-blockade may prevent the necessary facilitating effect of sympathetic activity on conduction. Beta 2 -adrenergic blockade results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients.
Adults: In man, absorption of metoprolol is rapid and complete. Plasma levels achieved are highly variable after oral administration. When administered orally, it exhibits stereoselective metabolism that is dependent on oxidation phenotype.
Elimination is mainly by biotransformation in the liver, and the plasma half-life ranges from approximately 3 to 7 hours. Consequently, no reduction in metoprolol succinate dosage is usually needed in patients with chronic renal failure. CYP2D6 can be inhibited by a number of drugs. Poor metabolizers and extensive metabolizers who concomitantly use CYP2D6 inhibiting drugs will have increased several-fold metoprolol blood levels, decreasing metoprolol's cardioselectivity [see Drug Interactions 7.
In comparison to conventional metoprolol, the plasma metoprolol levels following administration of TOPROL-XL are characterized by lower peaks, longer time to peak and significantly lower peak to trough variation.
The peak plasma levels following once-daily administration of TOPROL-XL average one-fourth to one-half the peak plasma levels obtained following a corresponding dose of conventional metoprolol, administered once daily or in divided doses. The bioavailability of metoprolol shows a dose-related, although not directly proportional, increase with dose and is not significantly affected by food following TOPROL-XL administration.
The pharmacokinetics of metoprolol were similar to those described previously in adults. Age, gender, race, and ideal body weight had no significant effects on metoprolol pharmacokinetics. Long-term studies in animals have been conducted to evaluate the carcinogenic potential of metoprolol tartrate.
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. There was no increase in malignant or total benign plus malignant lung tumors, nor in the overall incidence of tumors or malignant tumors. This 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.
In five controlled studies in normal healthy subjects, the same daily doses of TOPROL-XL and immediate-release metoprolol were compared in terms of the extent and duration of beta 1 - blockade produced. Both formulations were given in a dose range equivalent to mg of immediate-release metoprolol per day.
A sixth controlled study compared the beta 1 -blocking effects of a 50 mg daily dose of the two formulations. In each study, beta 1 -blockade was expressed as the percent change from baseline in exercise heart rate following standardized submaximal exercise tolerance tests at steady state. TOPROL-XL administered once a day, and immediate-release metoprolol administered once to four times a day, provided comparable total beta 1 -blockade over 24 hours area under the beta 1 -blockade versus time curve in the dose range mg.
For TOPROL-XL, the percent reduction in exercise heart rate was relatively stable throughout the entire dosage interval and the level of beta 1 -blockade increased with increasing doses from 50 to mg daily. In contrast to TOPROL-XL, immediate-release metoprolol given at a dose of mg once a day produced a significantly larger peak effect on exercise tachycardia, but the effect was not evident at 24 hours.
A controlled cross-over study in heart failure patients compared the plasma concentrations and beta 1 -blocking effects of 50 mg immediate-release metoprolol administered t.
A 50 mg dose of immediate-release metoprolol t. In controlled clinical studies, an immediate-release dosage form of metoprolol was an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics at dosages of mg daily. In controlled, comparative, clinical studies, immediate-release metoprolol appeared comparable as an antihypertensive agent to propranolol, methyldopa, and thiazide-type diuretics, and affected both supine and standing blood pressure.
Because of variable plasma levels attained with a given dose and lack of a consistent relationship of antihypertensive activity to drug plasma concentration, selection of proper dosage requires individual titration. 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.
In controlled clinical trials, an immediate-release formulation of metoprolol has been shown to be an effective antianginal agent, reducing the number of angina attacks and increasing exercise tolerance.
The dosage used in these studies ranged from to mg daily. Taking metoprolol with reserpine and monoamine oxidase inhibitors MAOIs may increase or add to the effects of metoprolol. They may also increase lightheadedness or slow your heart rate more. MAOIs can continue to interact with metoprolol for up to 14 days after taking them. Examples of MAOIs include:. Taking heart rhythm drugs with metoprolol can slow down your heart rate too much.
Examples of these drugs include:. Like metoprolol, these drugs are used to treat high blood pressure and several other heart problems. Combined with metoprolol, calcium channel blockers may slow your heart rate even more. Doctors sometimes use this combination under close supervision.
Drugs used to treat depression and other mood disturbances are processed in your body by the same systems as metoprolol. Using these drugs with metoprolol could increase the levels of metoprolol in your body. Alpha-blockers also lower blood pressure. They may decrease blood pressure too much when combined with metoprolol. Stopping the drug suddenly while also taking metoprolol can cause a big jump in blood pressure.
Ergot alkaloids, such as dihydroergotamine, narrow blood vessels to treat headaches. If you take them at the same time as metoprolol, they may cause dangerous narrowing of blood vessels.
Dipyridamole is used for heart testing. All possible dosages and forms may not be included here. Your dosage, form, and how often you take the drug will depend on:. Your body may process this drug more slowly.
Your doctor may start you on a lowered dosage so that too much of this drug does not build up in your body. Too much of the drug in your body can be dangerous.
Treatment with this drug is often started in the hospital with the intravenous formulation as soon as possible after a heart attack. Treatment with the oral medication as noted below is begun if your body tolerates the intravenous dosing. For people with liver disease: Liver disease may affect your dosage. Your doctor can tell you more. Disclaimer: Our goal is to provide you with the most relevant and current information.
However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice.
Always speak with your doctor or pharmacist about dosages that are right for you. Taking it again could be fatal cause death. A doctor may still prescribe it, but with careful monitoring. At higher doses, metoprolol can block different receptors on the breathing passages. This narrows the passages, which worsens asthma or COPD. For people with diabetes : Metoprolol may eliminate tremors and reduce heart rate.
Tremors and an increased heart rate are signs of low blood sugar. Without these signals, it becomes more difficult to recognize low blood sugar levels. For people with poor circulation: If you have poor circulation in your feet and hands, it may become worse when taking metoprolol.
Because metoprolol reduces blood pressure, you may get even less blood to these parts of your body. For pregnant women: Metoprolol is a category C pregnancy drug. That means two things:. For women who are breastfeeding: Metoprolol enters the breast milk and could be passed to your baby if you breastfeed while taking this drug.
Talk to your healthcare provider before breastfeeding. For seniors: Seniors may need a smaller dosage of metoprolol at first. The dosage may then increase gradually. For children: The immediate-release form of the drug has not been established as safe or effective in children. The extended-release form of this drug can be used to treat high blood pressure in children 6 years of age or older.
Metoprolol oral tablet can be used either as a short-term drug or a long-term drug. Also, if you suddenly stop taking metoprolol for high blood pressure, chest pain, or after a heart attack, you raise your risk of heart attack. Your blood pressure might fluctuate too often.
That might increase your risk for a heart attack. If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:.
But if your symptoms are severe, call or go to the nearest emergency room right away. What to do if you miss a dose: If you miss a dose, just take the next dose as planned. A prescription for this medication is not refillable. You or your pharmacy will have to contact your doctor for a new prescription if you need this medication refilled. There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.
0コメント