Логимакс

General characteristics. Structure:

1 tablet of the prolonged action, film coated, contains:
active agents: metoprolola of succinate of 47,5 mg, corresponding 39 mg of a metoprolol or 50 mg of a metoprolol of tartrate; felodipina of 5 mg
excipients: a gipromelloza of 150 mg, sodium aluminosilicate of 70,5 mg, lactose of anhydrous 42 mg, a hypro rod of 17,2 mg, a macrogoal глицерилгидроксистеарат 5 mg, cellulose of microcrystallic 4,5 mg, sodium of the stearylfumarating 3,7 mg, propyl gallate of 0,06 mg, silicon dioxide of 12,0 mg, ethyl cellulose of 13,0 mg; as a part of a film cover of a tablet: gipromelloza of 9,3 mg, macrogoal of 6000 2,3 mg, paraffin of 0,2 mg, titanium dioxide (E171) of 1,4 mg, dye ferrous oxide yellow (E172) of 0,13 mg, dye ferrous oxide red (E172) of 0,03 mg
Description
Round biconvex tablets, film coated, light orange color; on one party an engraving And
FG.

Pharmacological properties:

Pharmacodynamics. Логимакс® - the combined means which has hypotensive and anti-anginal effect. The complementary mechanism of effect of the selection beta1-adrenoblocker of a metoprolol (decrease in cordial emission) and a vazoselektivny blocker of "slow" calcium channels (BMKK) of a felodipin (decrease in the general peripheric vascular resistance) results in more expressed anti-hypertensive effect and the best portability in comparison with indicators which can be received at monotherapy metoprololy and felodipiny. Hypotensive effect of the drug Logimaks® remains within a day.
Metoprolol
Metoprolol is the cardioselective antagonist of beta1-adrenoceptors, does not influence in therapeutic doses the beta2-adrenoceptors localized, mainly, in peripheral vessels and bronchial tubes. Has insignificant membrane stabilizing effect and has no internal sympathomimetic activity.
Beta adrenoblockers have negative inotropic and chronotropic effect. Metoprolol reduces the stimulating effect of catecholamines by a myocardium and promotes an urezheniye of the heart rate (HR), decrease in cordial emission and the arterial pressure (AP). In a condition of a stress at hypersecretion of adrenaline does not interfere with a normal physiological vazodilatation. In therapeutic doses метопролол to a lesser extent exerts impact on muscles of bronchial tubes, than non-selective beta adrenoblockers. To a lesser extent, than non-selective beta adrenoblockers influences secretion of insulin and metabolism of carbohydrates in this connection, it can be appointed to patients with a diabetes mellitus. Metoprolol renders smaller effect on such cardiovascular reactions at a hypoglycemia, such as, tachycardia. At therapy metoprololy concentration of glucose in a blood plasma is recovered to normal value quicker, than at therapy by non-selective beta adrenoblockers. Metoprolol reduces raised by the ABP as in situation "oya", and "lying", and also at an exercise stress. At the beginning of therapy causes increase in the general peripheric vascular resistance (GPVR). However at prolonged treatment decrease in the ABP owing to decrease in OPSS at not changed cordial emission is noted. At patients with arterial hypertension метопролол reduces mortality from the cardiovascular reasons. Against the background of reception changes of indicators of water and electrolytic balance of blood are noted.
Felodipin
Felodipin – derivative dihydropyridine, is the selection BMKK and is intended for treatment of arterial hypertension and stable stenocardia.
Felodipin represents racemic mix.
Conductivity and sokratitelny ability of smooth muscles of vessels is suppressed by impact on calcium channels of cellular membranes.
Thanks to high selectivity concerning smooth muscles of arterioles, фелодипин in therapeutic doses does not render a negative inotropic effect on contractility or conductivity of a myocardium. Felodipin relaxes smooth muscles of respiratory tracts and makes insignificant impact on motility of digestive tract. At prolonged use does not render clinically significant effect on concentration of lipids in blood. At patients with a diabetes mellitus 2 types at use of a felodipin within 6 months are noted clinically significant influence on concentration of glikozilirovanny hemoglobin (HbA1c).
Felodipin can also appoint the patients with dysfunction of a left ventricle receiving standard therapy and patients with bronchial asthma, a diabetes mellitus, gout or a dislipidemiya.
Anti-hypertensive effect: decrease in the ABP at reception of a felodipin is caused by reduction of OPSS.
Felodipin effectively reduces the ABP at patients with arterial hypertension as in situation "lying", and "sitting", "standing", at rest and at an exercise stress. As фелодипин does not exert impact on smooth muscles of veins or adrenergic action, development of orthostatic hypotension does not happen. In an initiation of treatment, as a result of decrease in the ABP against the background of reception of a felodipin, temporary reflex increase in ChSS and cordial emission which is leveled at a combination with beta adrenoblockers can be observed. Action of a felodipin on the ABP and OPSS correlates with plasma concentration of a felodipin. After achievement of stable equilibrium concentration in a blood plasma of a felodipin the anti-hypertensive effect remains throughout an interdose interval not less than 24 hours.
Treatment felodipiny leads to regression of a hypertrophy of a left ventricle.
Felodipin reduces vascular resistance in kidneys, has natriuretic and diuretic effect and has no potassiumuretic effect (due to reduction of speed of a canalicular reabsorption of ions of sodium and water). Felodipin does not exert impact on a glomerular filtration rate and excretion of albumine.

Pharmacokinetics. Metoprolol
After intake метопролол it is completely soaked up in intestines. System bioavailability of a metoprolol in tablets with the slowed-down release of Betalok® of ZOK makes 30-40%. Is exposed to metabolism in a liver with formation of 3 main metabolites which do not have pharmacological activity and not having clinical value. Metoprolol is brought through kidneys. The elimination half-life averages 3,5 hours. About 5% of the accepted dose are removed in not changed look, other part of the accepted dose – in the form of metabolites. Communication with proteins of a blood plasma of low, about 5-10%.
Felodipin
The indicator of system bioavailability of a felodipin makes about 15% and does not depend on meal. Meal influences the speed of absorption of a felodipin, leading to increase in speed of achievement of the maximum concentration (Cmax) in a blood plasma approximately for 65%. Cmax in a blood plasma is reached in 3-5 hours after administration of drug inside. Communication with proteins of a blood plasma makes about 99%. Distribution volume in an equilibrium condition about 10 l/kg. The elimination half-life (T1/2) of a felodipin in a final phase about 25 hours, equilibrium concentration is reached in 5 days. Does not kumulirut. The general plasma clearance averages 1200 ml/min. At patients with the broken function of a liver and patients of advanced age concentration of a felodipin in a blood plasma increases. At the same time, the age only partially explains individual changes of plasma concentration of a felodipin. It is metabolized in a liver, all metabolites pharmacological are inactive. About 70% of the accepted dose are removed in the form of metabolites by kidneys, other part – through intestines. Less than 0,5% are removed by kidneys in not changed look. At a renal failure plasma concentration of a felodipin does not change, but cumulation of inactive metabolites is observed. Felodipin is not brought at a hemodialysis.
Metoprolol + Felodipin
Administration of drug of Logimaks® does not lead to change of bioavailability of active components, in comparison with a separate concomitant use of a metoprolol and a felodipin. Indicators of absorption do not depend on meal.

Indications to use:

Arterial hypertension (it can be applied in cases when treatment by beta adrenoblockers or BMKK derivative a dihydropyridinic row, applied in monotherapy, do not render clinically significant effect).

Route of administration and doses:

Inside, to accept in the morning, washing down with water. Not to divide, not to split up and not to chew a tablet. Tablets can be applied on an empty stomach or with a small amount of food with the low content of fats and carbohydrates.
The dose of the drug Logimaks® is selected individually. At the choice of an initial dose it is recommended to consider effect of earlier accepted doses of beta adrenoblockers or BMKK. Usually initial dose: on 1 tablet of the drug Logimaks® once a day. If necessary it is possible to increase a dose to 2 tablets in one step once a day.
Renal failure
The renal failure does not influence concentration of drug in a blood plasma. There is no need to adjust a drug dose for patients with a renal failure, however patients should be careful at purpose of drug with a heavy renal failure (KK less than 30 ml/min.) (see sections of "Contraindication" and "Special Instructions").
Abnormal liver function
Usually there is no need to adjust a drug dose for patients with cirrhosis as метопролол contacts blood proteins only in insignificant degree (5 - 10%). In the presence of symptoms of the expressed abnormal liver function (for example, the patients who underwent operations on porto-caval shunting) it is not necessary to take more than 1 pill of the drug Logimaks® a day. Patients of advanced age
There is usually enough 1 tablet of the drug Logimaks® once a day. If necessary it is possible to increase a dose to 2 tablets once a day.
Children
Experience of use of drug for children up to 18 years is absent.

Features of use:

It is necessary to be careful at combined use with cardiac glycosides. Логимакс® can strengthen symptoms of disturbance of peripheric circulation, for example, the "alternating" lameness. Extra care at the following states is required: a heavy renal failure (KK less than 30 ml/min.), an aortal stenosis, an abnormal liver function, the myocardial infarction complicated by an acute heart failure, arterial hypotension which can cause in predisposed patients myocardium ischemia, an acute metabolic acidosis.
It is not recommended to begin treatment with the drug Logimaks® at the patients who were earlier not receiving anti-hypertensive therapy.
It is not recommended to appoint drug to patients with the hidden or revealed heart failure with clinical manifestations without the corresponding therapy.
Use of the drug Logimaks® can exert impact on carbohydrate metabolism or mask a hypoglycemia, at the same time, at drug Logimaks® use the risk of impact on carbohydrate metabolism is less, than at use of non-selective beta adrenoblockers. In some cases, the available disturbances of AV of conductivity can amplify, leading to AV to blockade.
The patients accepting Logimaks® should not enter intravenously BMKK like verapamil.
Patients with Printsmetal's stenocardia have a frequency and weight of attacks of stenocardia can increase owing to a spasm of coronary vessels, the caused stimulation of alpha adrenoceptors. In this regard, this group of patients is not recommended to appoint non-selective beta adrenoblockers. It is necessary to apply the selection beta1-adrenoblockers with care.
At patients with bronchial asthma or chronic obstructive pulmonary disease it is necessary to perform the accompanying therapy of a beta2-adrenomimetikama. In case the patient begins to accept Logimaks®, increase in a dose of beta2-adrenomimetik can be required.
Against the background of reception of beta adrenoblockers the acute anaphylaxis can take more severe form. Use of Epinephrinum (adrenaline) in usually applied dose not always results in the expected therapeutic effect.
Patients with a pheochromocytoma are recommended to appoint alpha adrenoblockers in parallel with the drug Logimaks®.
Combined use of the drugs inducing CYP3A4 isoenzyme leads to considerable reduction of concentration of a felodipin in a blood plasma and to insufficient therapeutic effect of administration of drug (see the section "Interaction with Other Medicines and Other Types of Interaction"). It is necessary to avoid combined use of such drugs.
Combined use of the drugs inhibiting CYP3A4 isoenzyme leads to significant increase in concentration of a felodipin in a blood plasma.
It is necessary to avoid administration of drug of Logimaks® with grapefruit juice because of significant increase in concentration of a felodipin in a blood plasma.
It is necessary to avoid sharp cancellation of reception of beta adrenoblockers, especially at patients with high risk of cardiovascular complications, because of possible strengthening of symptoms of chronic heart failure and increase in risk of development of a myocardial infarction and sudden death. If necessary drug withdrawal of Logimaks® should be carried out gradually by a dose decline within 1-2 weeks. In case of surgical intervention it is necessary to warn the anesthesiologist that the patient accepts Logimaks®. It is not recommended to stop treatment by beta adrenoblockers to patients to whom surgical intervention is necessary. In case of surgical intervention it is necessary to warn the anesthesiologist about the received therapy by the drug Logimaks®.
It was reported about cases of a hyperplasia of a mucous membrane of language and gums after reception of a felodipin at patients with the expressed ulitis / парадонтитом. This side effect it is possible to avoid or reduce extent of its manifestation by means of respect for careful hygiene of an oral cavity.
Patients with a pheochromocytoma are recommended to appoint alpha adrenoblockers at the same time.
Influence on ability to drive the car and to work with the equipment
During therapy by the drug Logimaks® it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions (dizziness and increased fatigue can be observed).

Side effects:

The headache (11%), hypostasis of anklebones and erubescence of the person belong to the most often met side reactions at administration of drug of Logimaks®. These by-effects can be observed in an initiation of treatment or at increase in a dose, usually pass independently. The majority of these effects is explained by vazodilatiruyushchy properties of a felodipin.
It was reported about the following by-effects of the drug Logimaks®:

System	Often (≥1/100)	Infrequently (≥1/1 000, <1/100)	Seldom, (≥1/10 000, <1/1000)
The general	hypostasis of anklebones, headache dizziness, increased fatigue
Blood circulation	erubescence of the person
Alimentary system	nausea

 

It was reported about the following by-effects of a metoprolol:

System	Often (≥1/100)	Infrequently (≥1/1 000, <1/100)	Seldom (≥1/10 000, <1/1000)
The general	dizziness, headache, increased fatigue	stethalgia, increase in body weight	hyperhidrosis, hair loss, disturbance of flavoring feelings, reversible decrease in a libido
Hematology			thrombocytopenia
Cardiovascular system	cold snap of extremities, bradycardia, heart consciousness	reversible strengthening of symptoms of heart failure	disturbance of conductivity, arrhythmia, peripheral hypostases, faint
Alimentary system	abdominal pain, nausea, vomiting, diarrhea, lock
Integuments			hypersensitivity reactions, aggravation of a course of psoriasis, photosensitization
Liver			increase in activity of "hepatic" transaminases
Respiratory system		asthma, bronchospasm at patients with bronchial asthma or a bronkho-obstructive syndrome
Central nervous system		sleep disorder, paresthesias	"dreadful" dreams, depression, memory disturbance, decline in the ability to concentration of attention, excitability, feeling of alarm, a hallucination
Organ of sight			vision disorder, dryness and/or irritation of eyes
Acoustic organ			ring in ears

It was reported about separate cases of an arthralgia, hepatitis, a spasm of muscles, dryness of a mucous membrane of an oral cavity, conjunctivitis, rhinitis, gangrene at patients with heavy disturbances of peripheric circulation.

It was reported about the following by-effects of a felodipin:

System	Often (≥1/100)	Infrequently (≥1/1 000, <1/100)	Seldom (≥1/10 000, <1/1000)	Very seldom (<1/10 000)
The general		increased fatigue		fever
Blood circulation	the erubescence of the person which is followed by feeling of heat, hypostasis of anklebones	tachycardia, heartbeat		premature ventricular contraction, the expressed decrease in the ABP which is followed by tachycardia which can cause an aggravation of a course of stenocardia in predisposed patients, leykotsitoklasti-a chesky vasculitis
Endocrine system				hyperglycemia
Alimentary system		nausea, abdominal pain	vomiting	hyperplasia of a mucous membrane of language and gums, ulitis
Integuments		dieback, skin itch	small tortoiseshell	photosensitization, angioneurotic
				hypostasis in the form of hypostasis of lips or language
Immune system				hypersensitivity reactions
Liver				increase in activity of "hepatic" transaminases in blood serum
Musculoskeletal system			arthralgia, mialgiya
Central nervous system	headache	paresthesias, dizziness	faint, impotence / sexual dysfunction
Urinary system				frequent urination

Interaction with other medicines:

Joint reception with the means interacting with system of enzymes of P450 cytochrome can affect concentration of a metoprolol and felodipin in a blood plasma. Interaction between metoprololy and felodipiny as they are metabolized by means of various isoenzymes of system of P450 cytochrome is not noted.
Interaction with metoprololy
Metoprolol is substrate for CYP2D6 isoenzyme. The medicines inhibiting CYP2D6 isoenzyme such as quinidine, тербинафин, пароксетин, fluoxetine, sertraline, целекоксиб, пропафенон and дифенгидрамин, can change concentration of a metoprolol in a blood plasma. The drug Logimaks® dose decline at the combined use with these medicines can be required.
Interaction with felodipiny
Felodipin is substrate for CYP3A4 isoenzyme. The drugs inducing or inhibiting CYP3A4 isoenzyme exert considerable impact on concentration of a felodipin in a blood plasma.
The drugs inducing system of P450 cytochrome: Phenytoinum, carbamazepine, phenobarbital and rifampicin, and also drugs of the St. John's Wort which is made a hole strengthen metabolism of a felodipin due to induction of system of P450 cytochrome. Combined use of Phenytoinum, carbamazepine, phenobarbital and rifampicin concentration – time" leads to decrease in values of the area under a curve "(AUC) for 93% and Cmax of a felodipin for 82%. It is necessary to avoid combined use with CYP3A4 isoenzyme inductors.
The drugs inhibiting system of P450 cytochrome: antifungal means of an azolovy row (итраконазол, кетоконазол), makrolidny antibiotics (for example, erythromycin) and inhibitors of HIV protease are CYP3A4 isoenzyme inhibitors. At combined use of an itrakonazol of Cmax of a felodipin AUC - by 6 times increases by 8 times. At combined use of Cmax and AUC erythromycin of a felodipin increases approximately by 2,5 times. It is necessary to avoid combined use of a felodipin and inhibitors of an isoenzyme CYP3A4.
Juice of grapefruit inhibits fermental system of an isoenzyme CYP3A4. Use of a felodipin with grapefruit juice increases Cmax and AUC of a felodipin approximately twice. It is necessary to avoid combined use.
Takrolimus: фелодипин can cause increase in concentration of a takrolimus in a blood plasma. At combined use it is recommended to control concentration of a takrolimus in blood serum, dose adjustment of a takrolimus can be required.
Cyclosporine: at combined use of cyclosporine and a felodipin of Cmax of a felodipin increases by 150%, AUC increases by 60%. However, impact of a felodipin on pharmacokinetic indicators of cyclosporine is minimum.
Cimetidinum: combined use of Cimetidinum and felodipin leads to increase in Cmax and AUC of a felodipin by 55%.
Derivatives of barbituric acid: barbiturates (the research was conducted with fenofarbitaly) slightly strengthen metabolism of a metoprolol, owing to induction of microsomal enzymes of a liver.
It is necessary to avoid combined use of the drug Logimaks® with the following means:
Propafenon: at use of a propafenon the 4th the patients receiving treatment metoprololy noted increase in plasma concentration of a metoprolol by 2-5 times, at the same time at 2 patients the side effects characteristic of a metoprolol were noted. This interaction was confirmed during the research at 8 volunteers. Possibly, interaction is caused by inhibition propafenony, like quinidine, metabolism of a metoprolol by means of system of P4502D6 cytochrome. In view of the fact that пропафенон has properties of beta adrenoblocker combined use of the drug Logimaks® and a propafenona is not advisable.
Verapamil: the combination of beta adrenoblockers (an atenolol, propranolol and Pindololum) and verapamil can cause bradycardia and lead to decrease in the ABP. Verapamil and beta adrenoblockers have the complementary inhibiting effect on AV conductivity and function of a sinus node.
Antiarrhytmic means of the I class: antiarrhytmic means of the I class and beta adrenoblockers at simultaneous use can lead to summing
Dose adjustment of the drug Logimaks® can be required at simultaneous use with the following medicines: a negative inotropic effect that leads to serious hemodynamic side effects at patients with dysfunction of a left ventricle. Also it is necessary to avoid use of a similar combination for patients with a sick sinus syndrome and disturbance of AV of conductivity. Interaction is described on the example of Disopyramidum.
Difengidramin: дифенгидрамин reduces clearance of a metoprolol to an alpha gidroksimetoprolola by 2,5 times. Strengthening of action of a metoprolol is at the same time observed.
Clonidine: increase in the ABP at sharp cancellation of a clonidine can be more expressed at joint reception with beta adrenoblockers. At combined use, in case of cancellation of a clonidine, the termination of reception of beta adrenoblockers should be begun some days before cancellation of a clonidine.
Diltiazem: diltiazem and beta adrenoblockers mutually strengthen the inhibiting effect on AV conductivity and function of a sinus node. At a combination of a metoprolol with diltiazem cases of the expressed bradycardia were noted.
Non-steroidal anti-inflammatory drugs (NPVP): NPVP weaken anti-hypertensive effect of beta adrenoblockers. This interaction is most studied for indometacin. The specified interaction for a sulindak is noted. In researches with diclofenac of this reaction it was not noted.
Fenilpropanolamin: фенилпропаноламин (норэфедрин) in a single dose of 50 mg can cause increase in the diastolic ABP to pathological values in healthy volunteers. Propranolol generally interferes with the increase in the ABP caused fenilpropanolaminy. However beta adrenoblockers can cause reactions of paradoxical arterial hypertension in the patients receiving high doses of a fenilpropanolamin. It was reported about several cases of development of hypertensive crisis against the background of reception of a fenilpropanolamin.
Epinephrinum: it was reported about 10 cases of the expressed arterial hypertension and bradycardia at the patients who were accepting non-selective beta adrenoblockers (including Pindololum and propranolol) and receiving Epinephrinum. Interaction is noted also in group of healthy volunteers. It is supposed that similar reactions can be observed also at use of Epinephrinum together with local anesthetics at accidental hit in a vascular bed. It is supposed that this risk is much lower at use of cardioselective beta adrenoblockers.
Quinidine: quinidine inhibits metabolism of a metoprolol at special group of patients with a "bystry" hydroxylation (in Sweden about 90% of the population), causing, mainly, significant increase in plasma concentration of a metoprolol and strengthening beta адреноблокады. It is considered that similar interaction is characteristic also of other beta adrenoblockers in which metabolism P4502D6 cytochrome participates.
Amiodaronum: combined use of Amiodaronum and metoprolol can lead to the expressed sinus bradycardia. In view of extremely long elimination half-life of Amiodaronum (50 days), it is necessary to consider possible interaction later long time after cancellation of Amiodaronum.
Rifampicin: rifampicin can strengthen metabolism of a metoprolol, reducing plasma concentration of a metoprolol.
Cardiac glycosides: in combination with beta adrenoblockers can break AV conductivity and cause bradycardia.
Concentration of a metoprolol in a blood plasma can increase at the combined use with Cimetidinum, gidralaziny, selective serotonin reuptake inhibitors, such as пароксетин, fluoxetine and sertraline. The patients who are at the same time accepting метопролол and other beta adrenoblockers (in the form of eye drops) or inhibitors of a monoaminooxidase (MAO), have to be under careful observation. Against the background of reception of beta adrenoblockers inhalation anesthetics strengthen cardiodepressive action. Against the background of reception of beta adrenoblockers dose adjustment of the last can be required by the patients receiving hypoglycemic means for intake.

Contraindications:

Hypersensitivity to a metoprolol, a felodipin or other components of drug, and also other derivatives of dihydropyridine
Unstable stenocardia
Atrioventricular block of II and III degrees
Chronic heart failure in a decompensation stage (a fluid lungs, hypoperfusion or arterial hypotension, HSN III-IV of a functional class on NYHA classification) and continuous or discontinuous inotropic therapy by agonists beta аденорецепторов.
Bradycardia or the expressed arterial hypotension with existence of clinical symptoms
Sick sinus syndrome
Cardiogenic shock
The expressed disturbances of peripheric circulation (at threat of a gangrenosis)
Suspicion on an acute stage of a myocardial infarction (ChSS less than 45 уд. / min., an interval PQ more than 0,24 with or the systolic ABP less than 100 mm of mercury.)
Age up to 18 years (efficiency and safety are not established)
Pheochromocytoma (without simultaneous use of alpha adrenoblockers).
Lactose intolerance, deficit of lactase and syndrome of glyukozo-galaktozny malabsorption (drug contains lactose).
With care (comparing advantage/risk): the expressed renal failure (the clearance of creatinine (CC) less than 30 ml/min.), an aortal stenosis, an abnormal liver function, a myocardial infarction, arterial hypotension, an acute metabolic acidosis, chronic heart failure (the I-II functional class on NYHA classification), bronchial asthma, the chronic obstructive pulmonary disease (COPD), Printsmetal's stenocardia.
Use at pregnancy and during breastfeeding
Pregnancy
Логимакс® it should not be appointed at pregnancy.
Metoprolol can be applied at pregnancy and in the period of a lactation only in urgent cases when the advantage for mother exceeds potential risk for a fruit and/or the child. Beta adrenoblockers can cause bradycardia in a fruit, newborns and in the children who are on breastfeeding. It should be considered at the solution of a question of purpose of drug during the last trimester of pregnancy and just before childbirth.
There are no sufficient data about use of a felodipin for pregnant women now. Based on the data obtained on animals on disturbance of fetation, фелодипин it should not be appointed at pregnancy. BMKK can weaken reductions of a uterus at premature births, at the same time there are not enough data confirming increase in duration of physiological childbirth. The risk of development of a hypoxia of a fruit in the presence at mother of arterial hypotension and reduction of perfusion in a uterus due to redistribution of a blood-groove and a peripheral vazodilatation is possible.
Breastfeeding
Metoprolol and фелодипин are allocated in breast milk. In need of use of the drug Logimaks® in the period of a lactation, breastfeeding should be stopped.

Overdose:

Toxicity
Metoprolol: метопролол in a dose of 7,5 g caused intoxication with a lethal outcome in the adult. At 5 summer children who accepted 100 mg of a metoprolol after a gastric lavage symptoms of intoxication were not noted. Reception of 450 mg of a metoprolol by the teenager of 12 years led to moderate intoxication. Reception of 1,4 g and 2,5 g of a metoprolol by adults caused moderate and heavy intoxication, respectively. Reception of 7,5 g adult led to extremely heavy intoxication.
Felodipin: at use of 10 mg of a felodipin for the 2-year-old child insignificant intoxication was noted. 150-200 mg of a felodipin at 17 summer patients and 250 mg caused intoxication in the adult from insignificant to moderate degree. Possibly, фелодипин renders more significant effect on peripheric circulation, than on heart in comparison with other drugs of this pharmakoterapevtichesky group.
Overdose symptoms
In case of overdose by the prolonged dosage forms symptoms of intoxication are shown in 12-16 hours after reception, heavy symptoms can arise also in several days after reception.
Metoprolol: at overdose metoprololy the most serious are symptoms from cardiovascular system, however sometimes, especially at children and teenagers, symptoms from the central nervous system (CNS) can prevail and dysfunction of lungs, bradycardia, atrioventricular (AV) blockade of I-ΙΙΙ degrees, an asystolia, the expressed decrease in the ABP, weak peripheral perfusion, heart failure, cardiogenic shock; the apnoea, and also, increased fatigue, consciousness disturbance, a tremor, spasms, the increased sweating, paresthesias, a bronchospasm, nausea, vomiting, is possible an ezofagialny spasm, a hypoglycemia (especially at children) or a hyperglycemia, a hyperpotassemia; renal failure; passing myasthenic syndrome; the accompanying alcohol intake, anti-hypertensive means, quinidine or barbiturates can worsen a condition of the patient. The first signs of overdose can be observed in 20 min. - 2 hours after administration of drug.
Felodipin: at overdose the greatest influence of a felodipin on cardiovascular system is observed: bradycardia (sometimes tachycardia), the expressed decrease in the ABP, AV blockade, ventricular premature ventricular contraction, atrioventricular dissociation, an asystolia, fibrillation of ventricles; headache, dizziness, consciousness disturbance (or coma), spasms; asthma, fluid lungs and apnoea; development respiratory a distress syndrome at adults is possible; acidosis, hypopotassemia, hyperglycemia, perhaps hypocalcemia; "inflows" of blood to an upper half of a trunk, a hypothermia; nausea and vomiting.
Overdose treatment.
Metoprolol: reception of absorbent carbon, in case of need gastric lavage.
IMPORTANT! Atropine (0,25-0,5 mg in/in for adults, 10-20 mkg/kg for children) has to be appointed to a gastric lavage (because of risk of stimulation of a vagus nerve). If necessary maintenance of passability of respiratory tracts (intubation) and adequate ventilation of the lungs. Completion of volume of the circulating blood and infusion of a dextrose (glucose). Control of an ECG. Atropine of 1,0-2,0 mg in/in, if necessary repeat introduction (especially in case of vagal symptoms). In case of decrease in contractility of a myocardium infusional introduction of Dobutaminum or dopamine is shown. It is possible to apply a glucagon also. Addition to therapy of Epinephrinum (adrenaline) can be in certain cases effective. At arrhythmia and expansion of the QRS complex infusionally enter sodium solutions (chloride or a hydrocarbonate). Installation of an artificial pacemaker is possible. At a cardiac standstill owing to overdose resuscitation actions within several hours can be necessary. The symptomatic treatment is carried out.
Felodipin: reception of absorbent carbon, in case of need a gastric lavage, in some cases it is effective even at a late stage of intoxication. Symptomatic therapy.
IMPORTANT! Atropine (0,25-0,5 mg in/in for adults, 10-20 mkg/kg for children) has to be appointed to a gastric lavage (because of risk of stimulation of a vagus nerve). Control of an ECG. If necessary maintenance of passability of respiratory tracts and adequate ventilation of the lungs. Correction of indicators of an acid-base state and water and electrolytic balance of blood serum is shown. In case of bradycardia and AV of blockade appoint atropine of 0,5-1 mg in the adult (20-50 mkg/kg to children), if necessary repeat introduction, or at first enter изопреналин 0,05-0,1 mkg/kg/min. At acute intoxication at an early stage installation of an artificial pacemaker can be necessary. The expressed decrease in the ABP is adjusted in/in increase in volume of the circulating liquid. If necessary infusionally enter Epinephrinum (adrenaline) or a dopamine. At acute intoxication the glucagon can be appointed.
At a cardiac standstill owing to overdose resuscitation actions within several hours can be necessary. At spasms appoint diazepam. Other symptomatic treatment is carried out.

Storage conditions:

At a temperature not above 30 °C, in the place, unavailable to children. Period of validity 3 years. Not to apply after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action, film coated on 50 mg + 5 mg.
On 30 tablets in a plastic bottle. On one bottle in a cardboard pack with the application instruction.