Universal reference book for medicines
Product name: LOGIMAX ® (LOGIMAX)

Active substance: felodipine, metoprolol succinate

Type: Antihypertensive drug

Manufacturer: ASTRAZENECA (Sweden)
Composition, form of production and packaging
The tablets of the prolonged action, covered with a cover of
pink color with an apricot hue, round, biconcave, with engraving "A / FG" on one side.

1 tab.

felodipine 5 mg

metoprolol succinate 47.5 mg,

that acc.
the content of metoprolol tartrate 50 mg
Auxiliary substances: sodium aluminosilicate, lactose anhydrous, hypromellose, hydroxypropyl cellulose, ethyl cellulose, silicon dioxide, polyoxy-40-hydrogenated castor oil, microcrystalline cellulose, macrogol 6000, sodium stearyl fumarate, paraffin, propyl gallate, iron oxide yellow (E172), iron oxide red ( E172), titanium dioxide (E171), purified water.

30 pcs.
- plastic bottles (1) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2010.

PHARMACHOLOGIC EFFECT

Antihypertensive drug of combined composition.
Has antihypertensive, anti-anginal and antiarrhythmic effect.
The complementary mechanism of action of felodipine, reducing OPSS, and metoprolol, which reduces cardiac output, leads to a more pronounced antihypertensive effect and better tolerability than monotherapy with felodipine and metoprolol.
When taking LogiMax, blood pressure reduction is stable and effective throughout the interval between doses (24 h).
Felodipine

Felodipine - a derivative of dihydropyridine, is a vasoselective blocker of slow calcium channels and is intended for the treatment of arterial hypertension and stable angina.
Felodipine is a racemic mixture.
Conductivity and contractility of the smooth muscles of blood vessels are suppressed by affecting the calcium channels of cell membranes.
Due to the high selectivity for smooth muscle arterioles, felodipine in therapeutic doses does not have a negative inotropic effect on cardiac contractility or conduction.
The antihypertensive effect of felodipine is due to a decrease in OPSS.
Felodipine effectively reduces blood pressure in patients with arterial hypertension both in a horizontal position, and in a sitting and standing position, at rest and under physical exertion. Since felodipine has no effect on smooth veins musculature or adrenergic vasomotor control, orthostatic hypotension does not develop. At the beginning of treatment, as a result of lowering blood pressure on the background of felodipine, a temporary reflex increase in heart rate and cardiac output may be observed, which is leveled when combined with beta-blockers. The effect of felodipine on AD and OPSS is correlated with the plasma concentration of felodipine. After achieving a stable equilibrium concentration in felodipine plasma, the antihypertensive effect persists for 24 hours.
Treatment with felodipine leads to the reverse development of left ventricular hypertrophy.

Felodipine relaxes the smooth muscles of the respiratory tract.
It has been shown that felodipine exerts an insignificant effect on the gastrointestinal motility. With prolonged use, felodipine does not have a clinically significant effect on lipid content in the blood. In patients with type 2 diabetes mellitus, the use of felodipine for 6 months had no clinically significant effect on metabolic processes. Felodipine can also be administered to patients with reduced left ventricular function receiving standard therapy, and to patients with bronchial asthma, diabetes, gout, or hyperlipidemia.
Felodipine reduces vascular resistance in the kidneys, has a natriuretic and diuretic effect and has no potassium-uretic effect (due to a decrease in tubular reabsorption of sodium and water).
Felodipine has no effect on glomerular filtration and albumin excretion.
Metoprolol

Is metoprolol a cardioselective antagonist?
1- adrenoreceptors, does not affect therapeutic doses at? 2- adrenoreceptors, localized mainly in the peripheral vessels and bronchi. Has an insignificant membrane-stabilizing effect and does not possess internal sympathomimetic activity.
Beta-adrenoblockers have a negative inotropic and chronotropic effect.
Metoprolol reduces the stimulating effect of catecholamines on the myocardium and helps to reduce heart rate, cardiac output and blood pressure. In a state of stress with increased secretion of epinephrine, metoprolol does not interfere with normal physiological vasodilation.
In therapeutic doses metoprolol has a smaller contractile effect on the musculature of the bronchi than non-selective beta-blockers.

Metoprolol to a lesser extent than non-selective beta-blockers affects insulin secretion and carbohydrate metabolism, and therefore metoprolol can be prescribed to patients with diabetes mellitus.
Metoprolol has a lesser effect on such cardiovascular reactions with hypoglycemia, like tachycardia. When metoprolol therapy, the blood glucose level is restored to the normal level faster than with the therapy with nonselective beta-blockers.
Metoprolol reduces elevated blood pressure both in a standing position, and in a horizontal position, as well as with physical exertion.
At the beginning of therapy, metoprolol causes an increase in OPSS. However, with prolonged treatment there is a decrease in blood pressure due to a decrease in OPSS with unchanged cardiac output. In patients with hypertension metoprolol reduces mortality from cardiovascular complications.
Against the background of taking metoprolol there were no changes in the electrolyte balance of the blood.

PHARMACOKINETICS

Felodipine

Suction

The indicator of systemic bioavailability of felodipine is about 15% and does not depend on food intake.
Eating influences the rate of absorption of felodipine, resulting in an increase in Cmax in blood plasma by approximately 65%. C max in blood plasma is achieved 3-5 hours after taking the drug.
Distribution

Binding to plasma proteins is approximately 99%.
V d in the equilibrium state is approximately 10 l / kg. Do not cumulate. C ss is achieved after 5 days.
Metabolism

Felodipine is metabolized in the liver, all metabolites are pharmacologically inactive.

Excretion

T 1/2 of felodipine in the final phase - about 25 hours. The total plasma clearance is an average of 1.2 l / min.

About 70% of the accepted dose is excreted in the form of metabolites with urine, the rest - with feces.
Less than 0.5% is excreted in the urine unchanged.
Pharmacokinetics in special clinical cases

In patients with impaired liver function and elderly persons, the concentration of felodipine in the blood plasma increases.
At the same time, the age sign only partially explains the individual changes in the plasma concentration of felodipine.
If the renal function is impaired, the plasma concentration of felodipine does not change, but cumulation of inactive metabolites is observed.
Felodipine is not excreted in hemodialysis.
Metoprolol

Absorption and Metabolism

Metoprolol is completely absorbed from the digestive tract after ingestion.
It is metabolized in the liver with the formation of 3 major metabolites that do not have pharmacological activity and are not of clinical significance.
Excretion

About 5% of the dose of metoprolol is excreted unchanged by the kidneys, the rest is excreted as metabolites.

Felodipine + Metoprolol

Receiving Logimax does not lead to a change in the bioavailability of the components, as compared to the separate simultaneous administration of felodipine and metoprolol.
Absorption rates do not depend on food intake.
INDICATIONS

- arterial hypertension.

The drug can be used in cases when treatment with beta-adrenoblockers or slow calcium channel blockers dihydropyridine series, used as monotherapy, do not have a clinically significant effect.

DOSING MODE

The drug is prescribed inside.
Tablets should be taken in the morning, washed down with water, do not divide, crush or chew. The drug can be used on an empty stomach or with a small amount of food with a low content of fats and carbohydrates.
The dose of Logimax is selected individually.
When choosing the initial dose, it is recommended to take into account the effect of previously taken doses of beta-blockers or blockers of slow calcium channels.
For adults and elderly patients the initial dose is 1 tab.
1 time / day. If necessary, the dose can be increased (1 tablet 2 times / day).
Impaired renal function does not affect the concentration of the drug in the blood plasma.
There is no need to adjust the treatment regimen in patients with impaired renal function, but caution should be exercised in prescribing patients with severe renal insufficiency .
Usually, there is no need to adjust the treatment regimen in patients with cirrhosis ;
metoprolol binds to blood proteins only to a small extent (5-10%). In the presence of symptoms of a serious violation of liver function (for example, patients who underwent bypass surgery) should not exceed the dose of Logimax 5 mg / 47.5 mg.
The experience of using the drug in children is limited.

SIDE EFFECT

The incidence of adverse reactions was classified as follows: often (? 1/100), sometimes (? 1/1000, <1/100), rarely (? 1/10 000, <1/1000), very rarely (<1/10 000).

The most common side reactions when taking Logimax include headache (11%), swelling of the ankles, redness of the face, as well as headache, dizziness, fatigue, nausea.

These adverse reactions can be observed at the beginning of treatment or with increasing doses and usually pass on their own.
Most of these effects are due to the vasodilating properties of felodipine.
Felodipine

From the cardiovascular system: often - redness of the face, accompanied by a feeling of heat, swelling of the ankles;
sometimes tachycardia, palpitation; rarely - faint;very rarely - extrasystole, a decrease in blood pressure, accompanied by tachycardia, which in predisposed patients can cause exacerbation of angina, leukocytoplastic vasculitis.
From the side of the central nervous system: often - a headache;
sometimes paresthesia, dizziness.
On the part of the reproductive system: sometimes - impotence, sexual dysfunction.

From the digestive system: sometimes - nausea, pain in the abdomen;
rarely vomiting; very rarely - hyperplasia of the mucous membrane of the tongue and gums, gingivitis, an increase in the activity of hepatic enzymes in the blood serum.
Dermatological reactions: sometimes - exanthema, itching;
very rarely photosensitization.
From the musculoskeletal system: rarely - arthralgia, myalgia.

From the side of the urinary system: very rarely - frequent urination.

On the part of the endocrine system: very rarely - hyperglycemia.

Allergic reactions: rarely - hives;
very rarely - angioedema (lips or tongue), hypersensitivity reactions.
Other: less often - a feeling of fatigue;
very rarely - a fever.
There are some reports of sleep disturbances, but there is no connection with the use of felodipine.

There have been reports of cases of hyperplasia of the mucous membrane of the tongue and gums after taking felodipine in patients with severe gingivitis / periodontitis.
This side effect can avoid or reduce the degree of its manifestation with the help of careful oral hygiene.
Hyperglycemia, which is specific for this group of drugs, with felodipine was noted only in individual cases.

Metoprolol

From the side of the central nervous system and peripheral nervous system: often - dizziness, headache, fatigue;
sometimes - paresthesia, sleep disturbances; rarely - depression, decreased ability to concentrate, nightmarish dreams, memory impairment, increased nervous excitability, feelings of anxiety, hallucinations.
From the cardiovascular system: often - bradycardia, a feeling of palpitations, cold extremities;
sometimes - a reversible increase in the symptoms of heart failure;rarely - arrhythmias, fainting, swelling, conduction disorders (increase in the timing).
On the part of the digestive system: often - nausea, vomiting, abdominal pain, diarrhea, constipation;
rarely - an increase in the level of hepatic transaminases, a violation of taste sensations.
From the respiratory system: sometimes - shortness of breath, bronchospasm in patients with bronchial asthma or asthmatic diseases.

From the senses: rarely - visual impairment, dryness and / or eye irritation, ringing in the ears.

Dermatological reactions: rarely - hyperhidrosis, hair loss, exacerbation of psoriasis, photosensitivity.

From the hemopoietic system: rarely - thrombocytopenia.

Other: sometimes - weight gain, chest pain;
rarely - reversible violation of libido, hypersensitivity reactions.
Individual cases of arthralgia, hepatitis, muscle spasm, dry mouth, conjunctivitis, rhinitis, and gangrene have been reported in patients with severe peripheral circulation disorders.

CONTRAINDICATIONS

- AV blockade II and III degree;

- SSSU;

- Chronic heart failure in the stage of decompensation (pulmonary edema, hypoperfusion or arterial hypotension) and continuous or intermittent inotropic therapy with β-adrenoreceptor agonists;

- suspected acute stage of myocardial infarction (heart rate less than 45 bpm, PQ interval more than 0.24 s or systolic blood pressure less than 100 mm Hg);

- cardiogenic shock;

- unstable angina;

acute myocardial infarction;

- symptomatic bradycardia;

- arterial hypotension;

- pronounced obliterating violations of the peripheral circulation at a threat of gangrene development;

- Pregnancy;

- age under 18 years (effectiveness and safety not established);

- hypersensitivity to felodipine or metoprolol or other components of the drug.

With caution (comparing benefit / risk), the drug should be prescribed for renal failure of severe degree (CK <30 ml / min), aortic stenosis, hepatic dysfunction, myocardial infarction, arterial hypotension, acute metabolic acidosis, chronic heart failure, bronchial asthma.

In patients with bronchial asthma or chronic obstructive pulmonary disease, concomitant therapy with beta 2 -adrenomimetics is necessary.
In case the patient begins to take Logimax ® , an increase in the dose of beta 2 -adrenomimetics may be required.
PREGNANCY AND LACTATION

Logimax ® should not be administered during pregnancy.

At present, there is insufficient data on the use of felodipine in pregnant women.
Based on the data obtained on animals, felodipine should not be administered during pregnancy. Blockers of slow calcium channels can inhibit uterine contractions in preterm delivery, but at the same time, there is insufficient data to confirm an increase in the duration of physiological labor. There is a risk of fetal hypoxia in the presence of arterial hypotension in the mother and a decrease in perfusion in the uterus due to redistribution of blood flow and peripheral vasodilation.
Metoprolol can be used during pregnancy and lactation only in case of emergency.
Beta-adrenoblockers can cause bradycardia in the fetus, newborns and in infants who are breastfed. This should be taken into account when deciding whether to prescribe the drug in the third trimester of pregnancy and immediately before childbirth.
Felodipine and metoprolol penetrate into breast milk.
When taking felodipine in a nursing mother at therapeutic doses, only a small amount of the drug falls into the baby with breast milk. Inadequate experience with the use of felodipine in women during lactation does not exclude the risk of exposure to the drug on the child, and therefore it is not recommended to appoint felodipine to women during lactation. If continuation of therapy is necessary to achieve a clinical effect, consideration should be given to stopping breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER

Impaired renal function does not affect the concentration of the drug in the blood plasma.
There is no need to adjust the treatment regimen in patients with impaired renal function, but caution should be exercised in prescribing patients with severe renal insufficiency .
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Usually, there is no need to adjust the treatment regimen in patients with cirrhosis ;
metoprolol binds to blood proteins only to a small extent (5-10%). In the presence of symptoms of a serious violation of liver function (for example, patients who underwent bypass surgery) should not exceed the dose of Logimax 5 mg / 47.5 mg.
APPLICATION FOR CHILDREN

The experience of using the drug in children is limited.

APPLICATION IN ELDERLY PATIENTS

For elderly patients, the initial dose is 1 tab.
1 time / day. If necessary, the dose can be increased (1 tablet 2 times / day).
SPECIAL INSTRUCTIONS

Care should be taken when co-prescribing with digitalis preparations.

Logimax ® can enhance the symptoms of peripheral circulatory disorders.

Caution should be given to the drug with renal failure of severe degree (CK <30 ml / min), aortic stenosis, violations of liver function, acute myocardial infarction, acute myocardial infarction complicated by heart failure, arterial hypotension, which in predisposed patients can cause myocardial ischemia, acute metabolic acidosis.It is not recommended to start treatment with Logimax in patients who have not previously received antihypertensive therapy.

It is not recommended to prescribe the drug to patients with latent or identified heart failure without appropriate therapy.

Application Logimaksa may affect carbohydrate metabolism or mask hypoglycaemia, however, the application of risk Logimaksa impact on carbohydrate metabolism less than with nonselective beta-blockers.
In some cases, existing AV-conduction disturbances may increase, resulting in AV-blockade.
Patients receiving Logimaks ® , should not be administered in / calcium channel blockers slow verapamil type.
In patients with Prinzmetal angina frequency and severity of angina attacks may increase due to coronary artery spasm-induced stimulation of alpha-adrenergic receptors. In this connection, not recommended for non-selective beta-blockers of this group of patients. It should be used with caution in beta1 adrenoblokatory.
While taking beta-blockers anaphylactic shock may take a more severe form. Application of epinephrine (adrenaline), in the commonly used dosage does not always lead to the expected therapeutic effect.
Patients with pheochromocytoma recommended Simultaneity with Logimaksom prescribe alpha-blockers.
The combined use of drugs that induce CYP3A4 enzyme system results in a significant decrease in concentrations of felodipine in plasma and insufficient therapeutic effect of the drug. Concomitant administration of such drugs should be avoided.
The combined use of drugs which inhibit the CYP3A4 enzyme system results in a significant increase of felodipine concentration in blood plasma.
Avoid receiving Logimaksa with grapefruit juice due to a significant increase of felodipine concentration in blood plasma.
It is necessary to avoid abrupt withdrawal of beta-blockers, especially in patients at high risk due to the possible increase in symptoms of chronic heart failure and increase the risk of myocardial infarction and sudden death. If necessary cancellation Logimaksa be carried out by gradually reducing the dose for 1-2 weeks.
In the case of surgery, the anesthesiologist should be warned that the patient receives Logimaks ® . It is not recommended to stop the treatment of beta-blockers in patients who are to surgery.
Impact on the ability to drive vehicles and manage mechanisms

When driving and other lesson potentially dangerous activities which require high concentration and psychomotor speed reactions must be taken into account that dizziness and fatigue may occur in the application of Logimaksa.
OVERDOSE

Toxicity
When using Felodipine 10 mg in 2-year-old minor toxicity was noted child. Felodipine at a dose of 150-200 mg for a 17-year old patient in a dose of 250 mg in an adult intoxication caused by slight to moderate degree. Probably, felodipine has a more significant effect on peripheral circulation, than the heart, as compared to other drugs of the therapeutic group.
metoprololat a dose of 7.5 g in an adult caused lethal intoxication with. In 5-year-old child, who took 100 mg of metoprolol after gastric lavage not observed signs of intoxication. Metoprolol 450 mg of 12-year-old child led to moderate toxicity. Metoprolol at a dose of 1.4 g and 2.5 g of adults caused moderate to severe intoxication, respectively. Metoprolol dose of 7.5 g to adults resulted in extremely severe intoxication.
Symptoms
In the case of prolonged action drug overdose toxicity symptoms after 12-16 h after administration, severe symptoms may occur a few days after administration.
In overdose felodipineobserved the greatest effect on the cardiovascular system: bradycardia (sometimes tachycardia), marked reduction in blood pressure, AV-block, ventricular premature beats, atrioventricular dissociation, asystole, ventricular fibrillation, headache, dizziness, impairment of consciousness (coma), convulsions, shortness of breath, pulmonary edema (no heart) and apnea; may develop respiratory distress syndrome in adults; acidosis, hypokalemia, hyperglycemia, hypocalcemia, flushing, hypothermia, nausea and vomiting.
With an overdose of metoprololthe most serious are the symptoms of the cardiovascular system, but sometimes, especially in children and adolescents, may dominate the symptoms of the CNS and the suppression of lung function, bradycardia, AV-blockade of I-III degree, asystole, marked reduction in blood pressure, poor peripheral perfusion , heart failure, cardiogenic shock, inhibition of pulmonary function, sleep apnea, as well as increased fatigue, impaired consciousness, loss of consciousness, tremor, convulsions, sweating, paresthesia, bronchospasm, nausea, vomiting, possible aiseau agialny spasm, hypoglycaemia (especially in children) or hyperglycaemia, hyperkalaemia; effects on the kidneys; transient myasthenic syndrome. Concomitant intake of alcohol, antihypertensives, quinidine or barbiturates may aggravate the patient's condition.The first signs of overdose can be observed after 20 min - 2 h after dosing.
Treatment

Felodipine
Assignment activated charcoal, if necessary gastric lavage, in some cases is effective even at a late stage of intoxication. Symptomatic therapy.
Atropine (0.25-0.5 mg / in adults, 10-20 mg / kg for children) should be assigned to gastric lavage (due to the risk of stimulation of the vagus nerve). Are monitored ECG. If necessary - maintaining airway and adequate ventilation. It shows the correction of acid-base status and serum electrolytes. In the case of bradycardia and AV-blockade atropine administered at 0.5-1 mg / per adult (20-50 mg / kg for children), if necessary, repeat administration or isoprenaline initially administered in a dose 0.05-0.1 g / kg / min. In acute toxicity at an early stage may need to install an artificial pacemaker. Hypotension corrected on / in the liquid. If desired infusion administered epinephrine or dopamine. In acute toxicity can be administered glucagon.In cardiac arrest due to an overdose may require resuscitation measures for several hours. In convulsions diazepam prescribed. Pursue other symptomatic treatment.
Metoprolol
Assignment activated charcoal, if necessary gastric lavage.
Atropine (0.25-0.5 mg / in adults, 10-20 mg / kg for children) should be assigned to gastric lavage (due to the risk of stimulation of the vagus nerve). If necessary - to maintain airway patency (intubation) and adequate ventilation. Volume replacement and glucose infusion. Are monitored ECG. Assign atropine at a dose of 1-2 mg / in, if necessary, repeat administration (particularly in the case of vagal symptoms). In the case of (suppression) myocardial depression shown dobutamine infusion or dopamine. Glucagon can also be applied at a dose 50-50 mg / kg / in 1 min intervals. In some cases, it may be effective to add to the adrenaline therapy. If ventricular fibrillation and expanded (QRS) complex is administered by infusion solutions of sodium chloride or sodium bicarbonate. Installation of an artificial pacemaker.In cardiac arrest due to an overdose may require resuscitation measures for several hours. Terbutaline can be used for relief of bronchospasm (injection or by inhalation). Symptomatic treatment.
DRUG INTERACTION

Co-administration with the compounds interacting with the cytochrome P450 system can affect the concentration of felodipine and metoprolol in plasma. There was no interaction between felodipine and metoprolol as they are metabolized by various cytochrome P450 isozymes.
Felodipine
Felodipine is a substrate for CYP3A4. Drugs that inhibit or induce the CYP3A4, have a significant effect on the concentration of felodipine in plasma.
Drugs that induce isozymes of cytochrome P450 (phenytoin, carbamazepine, phenobarbital and rifampin, and St. John's wort tincture), increase of felodipine metabolism. The combined use of phenytoin, carbamazepine, phenobarbital and rifampin leads to a decrease in AUC values of 93% and C maxFelodipine is 82%. Avoid concomitant administration with inducers of CYP3A4.
Azole antifungals (itraconazole, ketoconazole), macrolide antibiotics (e.g. erythromycin) and HIV protease inhibitors are inhibitors of the enzyme CYP3A4 system. The joint appointment of itraconazole the C max of felodipine increased by 8 times, AUC - 6 times. When coadministered erythromycin C max and AUC felodipine increased approximately 2.5 times. Avoid joint destination felidipina and CYP3A4 inhibitors.
Grapefruit juice inhibits the CYP3A4 enzyme system. Application of felodipine with grapefruit juice increased C maxfelodipine and AUC of about 2 times. Avoid joint use.
Felodipine may cause an increase in the concentration of tacrolimus in the blood plasma. When the joint application it is recommended to control the concentration of tacrolimus in the blood serum may require adjustment of the dose of tacrolimus.
When co-administration of cyclosporine and felodipine C max felodipine is increased by 150%, AUC increased by 60%. However, the effects of felodipine on the pharmacokinetic parameters of cyclosporine minimum.
The combined use of cimetidine and felodipine leads to an increase in C max and AUC of felodipine at 55%.
Metoprolol
should be avoided Logimaksa joint appointment with the following drugs .
Barbiturates (study was conducted with fenofarbitalom) slightly increase the metabolism of metoprolol, due to enzyme induction.
When assigning propafenone 4 patients treated with metoprolol, metoprolol showed an increase in plasma concentrations 2-5 times, with 2 patients were observed side effects typical of metoprolol. This interaction was confirmed during studies on 8 volunteers. Probably due to inhibition of the interaction of propafenone, like quinidine, metoprolol metabolism by isozyme CYP2D6. Taking into account the fact that propafenone has the properties of a beta-blocker, a joint appointment Logimaksa and propafenone did not seem appropriate.
The combination of beta-blockers (atenolol, propranolol and pindolol) and verapamil may cause bradycardia and lead to a reduction in blood pressure. Verapamil and beta-blockers have mutually inhibitory effect on the AV-conduction and sinus node function.
Logimaksa combination with the following agents may require dose adjustments.
Antiarrhythmics of class I and beta-blockers can lead to the summation of negative inotropic effect, which may lead to serious adverse hemodynamic effects in patients with impaired left ventricular function. You should also avoid such a combination in patients with sick sinus syndrome and impaired AV-conduction. The reaction described in Example disopyramide.
Diphenhydramine reduces the clearance of metoprolol to? -gidroksimetoprolola 2.5 times. At the same time strengthening the metoprolol action observed.
Hypertensive reactions during abrupt cancellation of clonidine may be increased when co-administered beta-blockers. In a joint application, in the case of clonidine, discontinuation of beta-blockers should start several days before clonidine.
Diltiazem and beta-blockers reinforce inhibitory effect on AV-conduction and sinus node function. With the combination of metoprolol with diltiazem there were cases of severe bradycardia.
NSAIDs weaken the antihypertensive effect of beta-blockers. This reaction is most documented for indomethacin. There was no interaction for sulindac described. In studies with diclofenac described reactions were noted.
Phenylpropanolamine (norephedrine) in a single dose of 50 mg may cause an increase in diastolic blood pressure to pathological values in healthy volunteers. Propranolol generally prevents the increase in blood pressure caused by phenylpropanolamine. However, beta-blockers can cause paradoxical reaction of hypertension in patients receiving high doses of phenylpropanolamine. It reported several cases of hypertensive crisis while taking phenylpropanolamine.
It reported 10 cases of severe hypertension and bradycardia in patients treated with non-selective beta-adrenergic blockers (including pindolol and propranolol) and treated with epinephrine (adrenaline). The interaction observed in healthy volunteers group. It is assumed that similar reactions may occur and the application of epinephrine with local anesthetic together with a random contact with the bloodstream. It is expected that this risk is much lower with cardioselective beta-blockers.
Quinidine inhibits the metabolism of metoprolol in a special group of patients with rapid hydroxylation (in Sweden about 90% of the population), causing mostly a significant increase in the plasma concentration of metoprolol and the strengthening of the blockade? -adrenoceptor. It is believed that this interaction is typical for other beta-blockers, metabolism involving isozyme CYP2D6.
The combined use of amiodarone and metoprolol may lead to severe sinus bradycardia. Taking into account the extremely long T 1/2 amiodarone (50 days), you should take into account possible interactions take place some time after discontinuation of amiodarone.
Rifampicin may enhance metabolism of metoprolol, reducing the plasma concentration of metoprolol.
The concentration of metoprolol in the blood plasma can rise in the combined use with cimetidine, hydralazine, selective serotonin inhibitors, such as paroxetine, fluoxetine and sertraline.
Patients concurrently taking metoprolol and other beta blockers (eye drops) or MAO inhibitors must be monitored closely.
While taking beta-blockers, inhalation anesthetics enhance cardiodepressive action.
While taking beta-blockers, patients receiving oral hypoglycemic agents may require dose correction last.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

The drug should be stored out of reach of children at a temperature of no higher than 30 ° C.
Shelf life - 3 years.
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