Instructions for use of BETALOC
Metoprolol is a CYPD6 substrate. Drugs that inhibit CYPD6 may affect plasma concentrations of metoprolol. Examples include the following drugs:
- quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine. When prescribing these drugs, it may be necessary to reduce the dose of Betaloc.
Co-administration of Betaloc with the following drugs should be avoided:
- Barbituric acid derivatives:
Barbiturates (the study was conducted with phenobarbital) slightly increase the metabolism of metoprolol due to enzyme induction.
Propaphenone:
When propafenone was prescribed to four patients treated with metoprolol, an increase in the plasma concentration of metoprolol was observed by 2-5 times, while two patients experienced side effects characteristic of metoprolol. This interaction was confirmed in a study on 8 volunteers. The interaction is likely due to propafenone's inhibition, like quinidine, of the metabolism of metoprolol via the cytochrome P4502D6 system. Taking into account the fact that propafenone has the properties of a beta-blocker, the joint administration of metoprolol and propafenone seems appropriate.
Verapamil:
the combination of β-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and β-blockers have a complementary inhibitory effect on atrioventricular conduction and sinus node function.
The combination of Betaloc with the following drugs may require dose adjustment:
Class I antiarrhythmic drugs:
Class I antiarrhythmics and β-blockers may result in additive negative inotropic effects, which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with sick sinus syndrome and atrioventricular conduction disorder. The interaction is described using disopyramide as an example.
Amiodarone:
The combined use of amiodarone and metoprolol can lead to severe sinus bradycardia. Given the extremely long half-life of amiodarone (50 days), a possible interaction should be considered long after discontinuation of amiodarone.
Diltiazem:
Diltiazem and β-blockers mutually enhance the inhibitory effect on atrioventricular conduction and sinus node function. When metoprolol was combined with diltiazem, cases of severe bradycardia were observed.
Nonsteroidal anti-inflammatory drugs (NSAIDs):
NSAIDs weaken the antihypertensive effect of β-blockers. This interaction is best documented for indomethacin. There is no reported interaction observed for sulindac. In studies with diclofenac, the described reaction was not observed.
Diphenhydramine:
Diphenhydramine reduces the clearance of metoprolol to α-hydroxymetoprolol by 2.5 times. At the same time, an increase in the effect of metoprolol is observed.
Epinephrine (adrenaline):
Ten cases of severe hypertension and bradycardia have been reported in patients taking non-selective beta-blockers (including pindolol and propranolol) and receiving epinephrine (adrenaline). The interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions can be observed when epinephrine is used together with local anesthetics if it accidentally enters the vascular bed. It is assumed that this risk is much lower with the use of cardioselective beta-blockers.
Phenylpropanolamine:
Phenylpropanolamine (norephedrine) in a single dose of 50 mg can cause an increase in diastolic blood pressure to pathological values in healthy volunteers. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers may cause paradoxical hypertension reactions in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported while taking phenylpropanolamine.
Quinidine:
Quinidine inhibits the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden, approximately 90% of the population), causing mainly a significant increase in plasma concentrations of metoprolol and increased β-blockade. It is believed that a similar interaction is typical for other β-blockers in the metabolism of which cytochrome P4502D6 is involved.
Clonidine:
Hypertensive reactions during abrupt withdrawal of clonidine may be exacerbated by concomitant use of β-blockers. When used together, if clonidine is discontinued, discontinuation of β-blockers should begin several days before discontinuation of clonidine.
Rifampicin:
Rifampicin may increase the metabolism of metoprolol, reducing plasma concentrations of metoprolol.
The concentration of metoprolol in blood plasma may increase when combined with cimetidine, hydralazine, selective serotonin reuptake inhibitors such as paroxetine, fluoxetine and sertraline. Patients concomitantly taking metoprolol and other β-blockers (eye drops) or monoamine oxidase inhibitors (MAOIs) should be closely monitored. When taking β-blockers, inhalational anesthetics enhance the cardiodepressive effect. While taking β-blockers, patients receiving oral hypoglycemic agents may require dose adjustment of the latter. Cardiac glycosides, when used together with beta-blockers, can increase atrioventricular conduction time and cause bradycardia.
Betaloc®
Co-administration of Betaloc ®
with the following drugs should be avoided:
Barbituric acid derivatives:
Barbiturates (the study was conducted with phenofarbital) slightly increase the metabolism of metoprolol due to enzyme induction.
Propaphenone:
When propafenone was prescribed to four patients treated with metoprolol, an increase in the plasma concentration of metoprolol was observed by 2-5 times, while two patients experienced side effects characteristic of metoprolol. This interaction was confirmed in a study on 8 volunteers. The interaction is likely due to propafenone's inhibition, like quinidine, of the metabolism of metoprolol via the cytochrome P4502D6 system. Taking into account the fact that propafenone has the properties of a beta-blocker, the joint administration of metoprolol and propafenone does not seem appropriate.
Verapamil:
the combination of β-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and β-blockers have a complementary inhibitory effect on atrioventricular conduction and sinus node function.
The combination of Betaloc® with the following drugs may require dose adjustment:
Class I antiarrhythmic drugs:
Class I antiarrhythmics and β-blockers may result in additive negative inotropic effects, which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with sick sinus syndrome and impaired AV conduction. The interaction is described using disopyramide as an example.
Amiodarone:
The combined use of amiodarone and metoprolol can lead to severe sinus bradycardia. Given the extremely long half-life of amiodarone (50 days), a possible interaction should be considered long after discontinuation of amiodarone.
Diltiazem:
Diltiazem and β-blockers mutually enhance the inhibitory effect on AV conduction and sinus node function. When metoprolol was combined with diltiazem, cases of severe bradycardia were observed.
Nonsteroidal anti-inflammatory drugs (NSAIDs):
NSAIDs weaken the antihypertensive effect of β-blockers. This interaction is best documented for indomethacin. There is no reported interaction observed for sulindac. In studies with diclofenac, the described reaction was not observed.
Diphenhydramine:
Diphenhydramine reduces the clearance of metoprolol to α-hydroxymetoprolol by 2.5 times. At the same time, an increase in the effect of metoprolol is observed.
Epinephrine (adrenaline):
Ten cases of severe hypertension and bradycardia have been reported in patients taking non-selective beta-blockers (including pindolol and propranolol) and receiving epinephrine (adrenaline). The interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions can be observed when epinephrine is used together with local anesthetics if it accidentally enters the vascular bed. It is assumed that this risk is much lower with the use of cardioselective beta-blockers.
Phenylpropanolamine:
Phenylpropanolamine (norephedrine) in a single dose of 50 mg can cause an increase in diastolic blood pressure to pathological values in healthy volunteers. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, β-blockers may cause paradoxical hypertension reactions in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported while taking phenylpropanolamine.
Quinidine:
Quinidine inhibits the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden, approximately 90% of the population), causing mainly a significant increase in plasma concentrations of metoprolol and increased β-blockade. It is believed that a similar interaction is typical for other β-blockers in the metabolism of which cytochrome P4502D6 is involved.
Clonidine:
Hypertensive reactions during abrupt withdrawal of clonidine may be exacerbated by concomitant use of β-blockers. When used together, if clonidine is discontinued, discontinuation of β-blockers should begin several days before discontinuation of clonidine.
Rifampicin:
Rifampicin may increase the metabolism of metoprolol, reducing plasma concentrations of metoprolol.
The concentration of metoprolol in the blood plasma may increase when combined with cimetidine, hydralazine, selective serotonin inhibitors such as paroxetine, fluoxetine and sertraline.
Patients concomitantly taking metoprolol and other β-blockers (eye drops) or monoamine oxidase inhibitors (MAOIs) should be closely monitored.
When taking β-blockers, inhalational anesthetics enhance the cardiodepressive effect.
While taking β-blockers, patients receiving oral hypoglycemic agents may require dose adjustment of the latter.
Cardiac glycosides, when used together with beta-blockers, can increase atrioventricular conduction time and cause bradycardia.
Betaloc, 100 pcs., 100 mg, tablets
For solution for intravenous administration
Toxicity
Metoprolol at a dose of 7.5 g in an adult caused intoxication with a fatal outcome. A 5-year-old child who took 100 mg of metoprolol showed no signs of intoxication after gastric lavage. Taking 450 mg of metoprolol by a 12-year-old teenager resulted in moderate intoxication. Administration of 1.4 g and 2.5 g of metoprolol to adults caused moderate and severe intoxication, respectively. Taking 7.5 g by adults resulted in extremely severe intoxication.
Symptoms:
In case of metoprolol overdose, the most serious symptoms are those from the cardiovascular system, but sometimes, especially in children and adolescents, symptoms from the central nervous system and suppression of pulmonary function may predominate. Bradycardia, AV block I–III degree, asystole, marked decrease in blood pressure, weak peripheral perfusion, heart failure, cardiogenic shock. Depression of pulmonary function, apnea, as well as increased fatigue, impaired consciousness, loss of consciousness, tremor, convulsions, increased sweating, paresthesia, bronchospasm, nausea, vomiting, possible esophageal spasm, hypoglycemia (especially in children) or hyperglycemia, hyperkalemia; effects on the kidneys; transient myasthenic syndrome. Concomitant use of alcohol, antihypertensive drugs, quinidine or barbiturates may worsen the patient's condition.
The first signs of overdose can be observed 20 minutes - 2 hours after taking the drug.
Treatment:
administration of activated carbon, and, if necessary, gastric lavage.
IMPORTANT!
Atropine (0.25–0.5 mg IV for adults, 10–20 mcg/kg for children) should be given before gastric lavage (due to the risk of vagus nerve stimulation). If necessary, maintain airway patency (intubation) and adequate ventilation. Replenishment of blood volume and glucose infusion. ECG monitoring. Atropine - 1-2 mg IV, repeat administration if necessary (especially in case of vagal symptoms). In case of myocardial suppression (depression), infusion administration of dobutamine or dopamine is indicated. Glucagon 50–150 mcg/kg IV may also be given at 1-minute intervals. In some cases, adding epinephrine to therapy may be effective. For arrhythmia and an increase in the ventricular complex (QRS), sodium solutions (chloride or bicarbonate) are infused. It is possible to install an artificial pacemaker. Cardiac arrest due to an overdose may require resuscitation for several hours. Terbutaline (injected or inhaled) can be used to relieve bronchospasm. Symptomatic treatment is carried out.
For tablets
Symptoms:
the consequences of an overdose of Betaloc® can be a pronounced decrease in blood pressure, sinus bradycardia, AV block, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, impaired consciousness/coma, nausea, vomiting and cyanosis.
Concomitant use of alcohol, antihypertensive drugs, quinidine or barbiturates may worsen the patient's condition.
The first signs of overdose may appear within 20 minutes to 2 hours after taking the drug.
Treatment:
administration of activated carbon, and, if necessary, gastric lavage. In case of a pronounced decrease in blood pressure, bradycardia, or the threat of heart failure, a β1-adrenergic agonist (for example, dobutamine) should be administered intravenously at intervals of 2–5 minutes or by infusion until a therapeutic effect is achieved. If a selective β1-agonist is not available, IV dopamine or atropine sulfate can be administered to block the vagus nerve.
If therapeutic effect is not achieved, other sympathomimetics such as dobutamine or norepinephrine can be used.
Glucagon can be administered at a dose of 1–10 mg. Sometimes it may be necessary to use a pacemaker. To relieve bronchospasm, a β2-adrenergic agonist should be administered intravenously.
It must be taken into account that the doses of antidotes required to eliminate the symptoms that occur with an overdose of β-blockers are much higher than therapeutic doses, since β-adrenergic receptors are bound to the β-blocker.
Buy Betaloc solution for injection intravenously 1 mg/ml ampoule 5 ml No. 5 in pharmacies
Betaloc Buy Betaloc in pharmacies DOSAGE FORMS solution for intravenous administration 1 mg/ml
MANUFACTURERS AstraZeneca AB (Sweden) Senexi S.a.S. (France)
GROUP Beta1-blockers (cardioselective)
COMPOSITION Active substance - Metoprolol.
INTERNATIONAL NON-PROPENTED NAME Metoprolol
SYNONYMS Betaloc ZOK, Vasocardin, Corvitol 100, Corvitol 50, Methohexal, Metozok, Metocard, Metocor Adifarm, Metoprolol, Metoprolol Organics, Metoprolol-Acri, Metoprolol-Ratiopharm, Serdol, Egilok, Egilok retard, Egilok S, Emzok
PHARMACOLOGICAL ACTION Pharmacological action - hypotensive, antianginal, antiarrhythmic. Reduces cardiac output and systolic blood pressure, slows heart rate, weakens the stimulating effect of catecholamines on the myocardium during physical activity and mental stress, and prevents reflex orthostatic tachycardia. The antihypertensive effect is due to a decrease in cardiac output and renin synthesis, inhibition of the activity of the renin-angiotensin system and the central nervous system, restoration of baroreceptor sensitivity and, ultimately, a decrease in peripheral sympathetic influences. The hypotensive effect develops quickly (systolic blood pressure decreases after 15 minutes, maximum after 2 hours) and lasts for 6 hours. Diastolic blood pressure changes more slowly. The antianginal effect is a consequence of a decrease in the frequency and strength of heart contractions, energy costs and myocardial oxygen demand. Reduces the frequency and severity of attacks of ischemic heart disease. Has a moderate negative inotropic effect. Metoprolol tartrate is rapidly and almost completely absorbed when taken orally and undergoes intensive first-pass metabolism. It is quickly distributed in tissues, penetrates the blood-brain barrier, the placental barrier, and breast milk. Biotransforms in the liver, producing two active metabolites. It is excreted primarily by the kidneys in the form of metabolites. Pharmacokinetic parameters do not depend on the age of patients.
INDICATIONS FOR USE Moderate and moderate arterial hypertension (monotherapy or in combination with other antihypertensive drugs), coronary artery disease, hyperkinetic cardiac syndrome, heart rhythm disturbances (sinus tachycardia, ventricular and supraventricular arrhythmia, including paroxysmal tachycardia, supraventricular tachycardia, extrasystole, flutter and atrial fibrillation, atrial tachycardia), hypertrophic cardiomyopathy, mitral valve prolapse, myocardial infarction (prevention and treatment), migraine (prevention), thyrotoxicosis (complex therapy); treatment of akathisia caused by neuroleptics.
CONTRAINDICATIONS Hypersensitivity, AV block II and III degrees, sinoatrial block, acute or chronic (in the stage of decompensation) heart failure, sick sinus syndrome, severe sinus bradycardia (heart rate less than 60 beats/min), cardiogenic shock, arterial hypotension (systolic blood pressure less than 100 mm Hg), severe peripheral circulatory disorders, pregnancy, breastfeeding. Restricted for use in: diabetes mellitus, hypoglycemia, severe allergic history, metabolic acidosis, bronchial asthma, emphysema, non-allergic bronchitis, hyperthyroidism, psoriasis, pheochromocytoma, impaired liver and/or kidney function, myasthenia gravis, depression, general anesthesia, elderly and children age.
SIDE EFFECTS From the nervous system and sensory organs: weakness, dizziness and headache, decreased concentration, drowsiness/insomnia, nightmares, depression, muscle cramps, paresthesia, nervousness, anxiety, decreased libido, blurred vision, xerophthalmia, conjunctivitis, lethargy , increased fatigue, anxiety, confusion, amnesia/short-term memory loss, hallucinations, tinnitus, impaired taste. From the cardiovascular system and blood (hematopoiesis, hemostasis): bradycardia, palpitations, hypotension, cold extremities, heart failure, AV block, edema syndrome, chest pain, decreased myocardial contractility, arrhythmias, gangrene, impaired myocardial conduction, syncope, thrombocytopenia, leukopenia, agranulocytosis. From the gastrointestinal tract: nausea, abdominal pain, diarrhea or constipation, vomiting, dry mouth, liver dysfunction; flatulence, dyspepsia, heartburn, hepatitis. From the respiratory system: shortness of breath, bronchospasm, vasomotor rhinitis, dyspnea. From the skin: rash, degenerative skin changes, reversible alopecia, photosensitivity, exacerbation of psoriasis; itching, erythema, urticaria, hyperhidrosis. Other: weight loss, arthralgia, arthritis, myalgia, muscle weakness, Peyronie's disease.
INTERACTION Hypotension is potentiated by sympatholytics, nifedipine, nitroglycerin, diuretics, apressin and other antihypertensive drugs. Antiarrhythmic and anesthetic drugs increase the risk of bradycardia, arrhythmia, and hypotension. Digitalis preparations potentiate the slowing of AV conduction. Simultaneous intravenous administration of verapamil and diltiazem can provoke cardiac arrest. Beta-adrenergic agonists, aminophylline, cocaine, estrogens, indomethacin and other NSAIDs weaken the antihypertensive effect. Strengthens and prolongs the effect of antidepolarizing muscle relaxants. Combination with alcohol leads to a mutual strengthening of the inhibitory effect on the central nervous system. Allergens increase the risk of severe systemic allergic reactions or anaphylaxis. Changes the effectiveness of insulin and oral antidiabetic agents and increases the risk of hypoglycemia. Antacids, hydralazines, oral contraceptives, cimetidine, ranitidine, phenothiazines increase the level of metoprolol in the blood, rifampicin decreases it. Reduces the clearance of lidocaine and the effectiveness of beta2-adrenergic agonists (the dose of the latter must be increased). Incompatible with MAO type A inhibitors.
OVERDOSE Symptoms: arterial hypotension, acute heart failure, bradycardia, cardiac arrest, AV block, cardiogenic shock, bronchospasm, impaired breathing and consciousness/coma, nausea, vomiting, generalized convulsions, cyanosis (manifest 20 minutes - 2 hours after administration). Treatment: gastric lavage, symptomatic therapy: administration of atropine sulfate (0.5-2 mg intravenously quickly) - for bradycardia and impaired AV conduction; glucagon (1-10 mg IV, then IV drip 2-2.5 mg/h) and dobutamine - in case of decreased myocardial contractility; adrenomimetics (norepinephrine, adrenaline, etc.) - for arterial hypotension; diazepam (iv slowly) - to eliminate seizures; inhalation of beta-adrenergic agonists or intravenous injection of aminophylline to relieve bronchospastic reactions; cardiac stimulation.
SPECIAL INSTRUCTIONS In patients with chronic heart failure, myocardial contractility may deteriorate, necessitating the use of cardiac glycosides and/or diuretics with careful monitoring of hemodynamic status. Against the background of diabetes mellitus and hyperfunction of the thyroid gland, metoprolol can mask tachycardia caused by hypoglycemia or thyrotoxicosis. In patients with diabetes mellitus, dose adjustment of antidiabetic drugs and careful monitoring of glycemic levels is necessary. When performing surgery during treatment, the anesthetic agent with the least negative ionotropic effect should be the drug of choice. A more pronounced development of a hypersensitivity reaction and the absence of a therapeutic effect of usual doses of adrenaline against the background of a burdened allergic history are possible. In patients with pheochromocytoma, use is possible only in conjunction with alpha-adrenolytics. Stop taking metoprolol 2-3 days before birth (risk of developing bradycardia, hypotension and hypoglycemia in the newborn); in exceptional cases, newborns after birth should be under medical supervision for 48-72 hours. When discontinuing treatment, the dose should be reduced gradually over 10-14 days. Patients with coronary artery disease should be under close medical supervision during this period. Use with caution while working for vehicle drivers and people whose profession involves increased concentration. During treatment, test results may change during laboratory tests.
STORAGE CONDITIONS List B. In a place protected from light, at room temperature.
Betaloc ZOK, 25 mg, delayed-release, film-coated tablets, 14 pcs.
Metoprolol is a CYP2D6 substrate, and therefore drugs that inhibit CYP2D6 (quinidine, terbinafine, paroxetine, fluoxetine, sertraline, celecoxib, propafenone and diphenhydramine) may affect the plasma concentrations of metoprolol.
The combined use of Betalok® ZOK with the following drugs should be avoided.
Derivatives of barbituric acid.
Barbiturates (study conducted with pentobarbital) increase the metabolism of metoprolol due to enzyme induction.
Propaphenone.
When propafenone was prescribed to four patients treated with metoprolol, an increase in plasma concentrations of metoprolol was observed by 2-5 times, while two patients experienced side effects characteristic of metoprolol. This interaction was confirmed in a study of data from 8 volunteers. The interaction is likely due to the inhibition by propafenone, like quinidine, of the metabolism of metoprolol through the cytochrome P450 2D6 system. Taking into account the fact that propafenone has the properties of a beta-blocker, the joint administration of metoprolol and propafenone does not seem appropriate.
Verapamil.
The combination of β-blockers (atenolol, propranolol and pindolol) and verapamil can cause bradycardia and lead to a decrease in blood pressure. Verapamil and β-blockers have complementary inhibitory effects on AV conduction and sinus node function.
The combination of Betaloc® ZOK with the following drugs may require dose adjustment.
Amiodarone.
The combined use of amiodarone and metoprolol can lead to severe sinus bradycardia. Taking into account the extremely long T1/2 of amiodarone (50 days), the possible interaction should be considered long after discontinuation of amiodarone.
Class I antiarrhythmic drugs.
Class I antiarrhythmics and β-blockers may result in additive negative inotropic effects, which can lead to serious hemodynamic side effects in patients with impaired left ventricular function. This combination should also be avoided in patients with sick sinus syndrome and impaired AV conduction. The interaction is described using disopyramide as an example.
NSAIDs.
NSAIDs weaken the antihypertensive effect of β-blockers. This interaction has been documented for indomethacin. It is likely that the described interaction will not be observed with sulindac. Negative interactions have been noted in studies with diclofenac.
Diphenhydramine.
Diphenhydramine reduces the clearance of metoprolol to α-hydroxymetoprolol by 2.5 times. At the same time, an increase in the effect of metoprolol is observed.
Diltiazem.
Diltiazem and β-blockers mutually enhance the inhibitory effect on AV conduction and sinus node function. When metoprolol was combined with diltiazem, cases of severe bradycardia were observed.
Epinephrine (adrenaline).
Ten cases of severe hypertension and bradycardia have been reported in patients taking non-selective beta-blockers (including pindolol and propranolol) and receiving epinephrine (adrenaline). The interaction was also observed in the group of healthy volunteers. It is assumed that similar reactions can be observed when epinephrine is used together with local anesthetics if it accidentally enters the vascular bed. It is assumed that this risk is much lower with the use of cardioselective beta-blockers.
Phenylpropanolamine.
Phenylpropanolamine (norephedrine) in a single dose of 50 mg can cause an increase in blood pressure to pathological values in healthy volunteers. Propranolol mainly prevents the increase in blood pressure caused by phenylpropanolamine. However, β-blockers may cause paradoxical hypertension reactions in patients receiving high doses of phenylpropanolamine. Several cases of hypertensive crisis have been reported while taking phenylpropanolamine.
Quinidine.
Quinidine inhibits the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden, approximately 90% of the population), causing mainly a significant increase in plasma concentrations of metoprolol and increased β-blockade. It is believed that a similar interaction is typical for other β-blockers, the metabolism of which involves cytochrome P450 2D6.
Clonidine.
Hypertensive reactions during abrupt withdrawal of clonidine may be exacerbated by concomitant use of beta-blockers. When used together, if clonidine is discontinued, discontinuation of beta-blockers should begin several days before discontinuation of clonidine.
Rifampicin.
Rifampicin may increase the metabolism of metoprolol, reducing plasma concentrations of metoprolol.
Patients concomitantly taking metoprolol and other beta-blockers (eye drops) or MAO inhibitors should be closely monitored. When taking β-blockers, inhalational anesthetics enhance the cardiodepressive effect. While taking β-blockers, patients receiving oral hypoglycemic agents may require dose adjustment of the latter.
Plasma concentrations of metoprolol may increase when taking cimetidine or hydralazine.
Cardiac glycosides, when used in combination with beta-blockers, can increase AV conduction time and cause bradycardia.
