Concor® AM
For amlodipine:
Amlodipine can be safely used for the treatment of arterial hypertension together with thiazide diuretics, alpha-blockers, beta-blockers or ACE inhibitors. In patients with stable angina, amlodipine can be combined with other antianginal agents, for example, long- or short-acting nitrates, beta-blockers.
Unlike other BMCCs, no clinically significant interaction with amlodipine (III generation BMCCs) was detected when used together with non-steroidal anti-inflammatory drugs (NSAIDs)
, including with
indomethacin
.
It is possible to enhance the antianginal and hypotensive effects of BMCC when used together with thiazide and loop diuretics, ACE inhibitors, beta-blockers and nitrates
, as well as enhancing their hypotensive effect when used together with alpha1-blockers and neuroleptics. Although negative inotropic effects have generally not been observed in amlodipine studies, some CBMCs may enhance the negative inotropic effects of antiarrhythmic drugs that cause QT prolongation (eg, amiodarone and quinidine).
Amlodipine can also be safely used concomitantly with antibiotics and oral hypoglycemic agents.
Single dose of 100 mg sildenafil
in patients with essential hypertension does not affect the pharmacokinetic parameters of amlodipine.
Repeated use of amlodipine 10 mg and atorvastatin
at a dose of 80 mg is not accompanied by significant changes in the pharmacokinetics of atorvastatin.
Simvastatin
: Simultaneous repeated use of amlodipine at a dose of 10 mg and simvastatin at a dose of 80 mg leads to an increase in simvastatin exposure by 77%. In such cases, the dose of simvastatin should be limited to 20 mg.
Ethanol (beverages containing alcohol):
amlodipine with single and repeated use at a dose of 10 mg does not affect the pharmacokinetics of ethanol.
Antivirals (ritonavir):
increases plasma concentrations of BMCC, including amlodipine.
Neuroleptics and isoflurane
: increased hypotensive effect of dihydropyridine derivatives.
Calcium preparations
may reduce the effect of BMCC.
When combined with BMCC and lithium preparations
(no data available for amlodipine), possibly increasing the manifestation of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).
Studies of concomitant use of amlodipine and cyclosporine
in healthy volunteers and all groups of patients, with the exception of patients after kidney transplantation, were not carried out. Various studies of the interaction of amlodipine with cyclosporine in patients after kidney transplantation show that the use of this combination may not lead to any effect, or increase the minimum concentration of cyclosporine to varying degrees, up to 40%. These data should be taken into account and cyclosporine concentrations should be monitored in this group of patients when cyclosporine and amlodipine are co-administered.
Does not affect serum digoxin
and its renal clearance.
Does not significantly affect the action of warfarin
(prothrombin time).
Cimetidine
does not affect the pharmacokinetics of amlodipine.
in vitro studies
amlodipine does not affect the binding of digoxin, phenytoin, warfarin and indomethacin to plasma proteins.
Grapefruit juice:
A simultaneous single dose of 240 mg of grapefruit juice and 10 mg of amlodipine orally is not accompanied by a significant change in the pharmacokinetics of amlodipine. However, it is not recommended to use grapefruit juice and amlodipine at the same time, since genetic polymorphism of the CYP3A4 isoenzyme may increase the bioavailability of amlodipine and, as a result, enhance the hypotensive effect.
Aluminum or magnesium containing antacids:
their single dose does not have a significant effect on the pharmacokinetics of amlodipine.
CYP3A inhibitors4:
with simultaneous use of diltiazem at a dose of 180 mg and amlodipine at a dose of 5 mg in patients from 69 to 87 years of age with arterial hypertension, an increase in the systemic exposure of amlodipine by 57% was observed.
The simultaneous use of amlodipine and erythromycin in healthy volunteers (from 18 to 43) does not lead to significant changes in the exposure of amlodipine (an increase in the area under the curve of “slow” calcium channels (SCCC) such as verapamil and, to a lesser extent, diltiazem, when used simultaneously with bisoprolol may lead to a decrease in myocardial contractility, a pronounced decrease in blood pressure and impaired AV conduction. In particular, intravenous administration of verapamil to patients taking beta-blockers can lead to severe arterial hypotension and AV blockade.
Centrally acting antihypertensives (such as clonidine, methyldopa, moxonidine , rilmenidine)
when used simultaneously with bisoprolol, they can lead to a decrease in heart rate and a decrease in cardiac output, as well as vasodilation due to a decrease in central sympathetic tone. Abrupt withdrawal, especially before discontinuation of beta-blockers, may increase the risk of developing rebound hypertension.
Combinations requiring caution
BMCA dihydropyridine derivatives (for example, nifedipine)
when used simultaneously with bisoprolol, they may increase the risk of developing arterial hypotension. In patients with CHF, the risk of subsequent deterioration in cardiac contractility cannot be excluded.
Class I antiarrhythmics (eg, quinidine, disopyramide, lidocaine, phenytoin, flecainide, propafenone)
when used simultaneously with bisoprolol, they can reduce AV conductivity and myocardial contractility.
Class III antiarrhythmics (eg, amiodarone)
may increase AV conduction disturbances.
Parasympathomimetics
when used simultaneously with bisoprolol, they may increase AV conduction disturbances and increase the risk of developing bradycardia.
The effect of beta-blockers for topical use
(for example, eye drops for the treatment of glaucoma)
may enhance the systemic effects of bisoprolol (lowering blood pressure, lowering heart rate).
Hypoglycemic effect of insulin or oral hypoglycemic agents
may intensify. Beta blockade may mask signs of hypoglycemia, particularly tachycardia. Such interactions are more likely when using non-selective beta-blockers.
Means for general anesthesia
may weaken reflex tachycardia and increase the risk of developing arterial hypotension (see section "Special Instructions").
Cardiac glycosides
when used simultaneously with bisoprolol, they can lead to an increase in AV conduction time and the development of bradycardia.
Nonsteroidal anti-inflammatory drugs
(NSAIDs)
may reduce the antihypertensive effect of bisoprolol.
Concomitant use of bisoprolol with beta-agonists (for example, isoprenaline, dobutamine)
may lead to a decrease in the effect of both drugs.
The combination of bisoprolol with adrenergic agonists
that affect beta and alpha adrenergic receptors (for example, norepinephrine, epinephrine)
may enhance the vasoconstrictor effects of these drugs that occur with the participation of alpha adrenergic receptors, leading to an increase in blood pressure. Such interactions are more likely when using non-selective beta-blockers.
Antihypertensives, as well as other drugs with possible antihypertensive effects (eg tricyclic antidepressants, barbiturates, phenothiazines)
, may enhance the antihypertensive effect of bisoprolol.
Combinations to consider
Mefloquine
when used simultaneously with bisoprolol, it may increase the risk of bradycardia.
MAO inhibitors
(with the exception of MAO-B inhibitors) may enhance the antihypertensive effect of beta-blockers. Concomitant use may also lead to the development of a hypertensive crisis.
Rifampicin
slightly shortens the half-life (T1/2) of bisoprolol. As a rule, no dose adjustment is required.
Ergotamine derivatives
when used simultaneously with bisoprolol, they increase the risk of developing peripheral circulatory disorders.
Concor AM tablets 5+10 mg 30 pcs. in Nizhnevartovsk
Amlodipine:
Suction:
Amlodipine is well absorbed after oral administration. The maximum concentration in the blood plasma is observed after 6-12 hours. Taking the drug with food does not affect its absorption. Absolute bioavailability is 64 - 80%.
Distribution:
The apparent volume of distribution is 21 l/kg. Equilibrium concentration in blood plasma (5-15 ng/ml) is achieved 7-8 days after starting the drug. In vitro studies have shown that circulating amlodipine is approximately 93-98% bound to plasma proteins.
Metabolism and excretion:
Amlodipine undergoes extensive metabolism in the liver. Approximately 90% of the dose taken is converted into inactive pyridine derivatives. Approximately 10% of the dose taken is excreted unchanged in the urine. Approximately 60% of the amount of inactive metabolites is excreted by the kidneys and 20-25% through the intestines. The decrease in plasma concentration is biphasic. The terminal half-life is approximately 35-50 hours, allowing the drug to be administered once daily. The total clearance is 7 ml/min/kg (25 l/h in a patient weighing 60 kg). In elderly patients it is 19 l/h.
In elderly patients and patients with renal impairment, no significant changes in the pharmacokinetics of amlodipine were observed.
Due to decreased clearance, patients with hepatic impairment should be given lower initial doses.
Bisoprolol:
Suction.
Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to negligible first-pass metabolism through the liver (at approximately 10%) is approximately 90% after oral administration. Food intake does not affect bioavailability. Bisoprolol exhibits linear kinetics, with its plasma concentrations being proportional to the dose taken in the range from 5 to 20 mg. The maximum concentration in blood plasma is achieved after 2-3 hours.
Distribution.
Bisoprolol is distributed quite widely. The volume of distribution is 3.5 l/kg. The binding to plasma proteins reaches approximately 30%.
Metabolism.
Metabolized via the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and are excreted by the kidneys. The main metabolites found in blood plasma and urine do not exhibit pharmacological activity. Data obtained from experiments with human liver microsomes in vitro show that bisoprolol is metabolized primarily by the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role.
Excretion.
The clearance of bisoprolol is determined by the balance between excretion by the kidneys unchanged (about 50%) and metabolism in the liver (about 50%) to metabolites, which are also excreted by the kidneys. The total clearance is 15 l/hour. The half-life is 10-12 hours.
Concor AM tablet 10 mg+10 mg x30
Concor AM tablet, 10 mg+10 mg x30, ATX code: C07FB07 (Bisoprolol in combination with other antihypertensive drugs)
Active substances
amlodipine (amlodipine) Rec.INN registered by WHO bisoprolol (bisoprolol) Rec.INN registered by WHO
Dosage forms
CONCOR® AM
Tabletkireg. No.: LP-001137 dated 03.11.11 - Valid
Release form, composition and packaging
The tablets are white or almost white, oblong, slightly biconvex, scored on one side and engraved “MS” on the other side, odorless.
1 tab.
bisoprolol fumarate 5 mg
amlodipine besilate 6.95 mg,
which corresponds to the content of amlodipine 5 mg
Excipients: microcrystalline cellulose - 130.55 mg, sodium carboxymethyl starch (type A) - 5 mg, magnesium stearate - 1.5 mg, colloidal anhydrous silicon dioxide - 1 mg.
The tablets are white or almost white, round, flat, beveled, scored on one side and engraved “MS” on the other side, odorless.
1 tab.
bisoprolol fumarate 5 mg
amlodipine besilate 13.9 mg,
which corresponds to the content of amlodipine 10 mg
Excipients: microcrystalline cellulose - 261.1 mg, sodium carboxymethyl starch (type A) - 10 mg, magnesium stearate - 3 mg, colloidal anhydrous silicon dioxide - 2 mg.
The tablets are white or almost white, oval, slightly biconvex, scored on one side and engraved “MS” on the other side, odorless.
1 tab.
bisoprolol fumarate 10 mg
amlodipine besilate 6.95 mg,
which corresponds to the content of amlodipine 5 mg
Excipients: microcrystalline cellulose - 263.05 mg, sodium carboxymethyl starch (type A) - 10 mg, magnesium stearate - 3 mg, colloidal anhydrous silicon dioxide - 2 mg.
The tablets are white or almost white, round, slightly biconvex, scored on one side and engraved “MS” on the other side, odorless.
1 tab.
bisoprolol fumarate 10 mg
amlodipine besilate 13.9 mg,
which corresponds to the content of amlodipine 10 mg
Excipients: microcrystalline cellulose - 261.1 mg, sodium carboxymethyl starch (type A) - 10 mg, magnesium stearate - 3 mg, colloidal anhydrous silicon dioxide - 2 mg.
Clinical-pharmacological group: Antihypertensive drug Pharmaco-therapeutic group: BMCC
pharmachologic effect
Combined antihypertensive drug. It has pronounced antihypertensive and antianginal effects due to the complementary action of two active substances: a slow calcium channel blocker (SCBC) - amlodipine and a selective beta1-blocker - bisoprolol.
Amlodipine
Amlodipine blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (more into vascular smooth muscle cells than into cardiomyocytes).
The antihypertensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle cells, which leads to a decrease in peripheral vascular resistance.
The mechanism of antianginal action is not fully understood; it may be associated with the following two effects.
1. The expansion of peripheral arterioles reduces peripheral vascular resistance, i.e. afterload. Since amlodipine does not cause reflex tachycardia, myocardial energy and oxygen consumption is reduced.
2. Dilatation of large coronary arteries and coronary arterioles improves oxygen supply to both normal and ischemic areas of the myocardium. Thanks to these effects, the supply of oxygen to the myocardium is improved, even with spasm of the coronary arteries (Prinzmetal's angina or unstable angina).
In patients with arterial hypertension, taking the drug once a day causes a clinically significant decrease in blood pressure in the supine and standing positions throughout the entire 24-hour interval between doses of the drug. Due to the slow development of the antihypertensive effect of amlodipine, it does not cause acute arterial hypotension.
In patients with angina pectoris, taking the drug once a day increases the total time of physical activity, the time before the development of an angina attack, as well as the time until a significant decrease in the ST interval, and also reduces the frequency of angina attacks and the need for sublingual nitroglycerin.
No negative effect of amlodipine on the metabolism of plasma lipids, blood glucose and serum uric acid was detected.
Bisoprolol
Bisoprolol is a selective beta1-blocker, without its own sympathomimetic activity, and does not have a membrane-stabilizing effect.
It has only slight affinity for c2-adrenergic receptors of the smooth muscles of the bronchi and blood vessels, as well as for β2-adrenergic receptors involved in the regulation of metabolism. Therefore, bisoprolol generally does not affect airway resistance and metabolic processes in which β2-adrenergic receptors are involved.
The selective effect of the drug on β1-adrenergic receptors persists beyond the therapeutic range.
Bisoprolol does not have a pronounced negative inotropic effect.
The maximum effect of the drug is achieved 3-4 hours after oral administration. Even when bisoprolol is prescribed once a day, its therapeutic effect persists for 24 hours due to 10-12 hours T1/2 from blood plasma. As a rule, the maximum antihypertensive effect is achieved 2 weeks after the start of treatment.
Bisoprolol reduces the activity of the sympathoadrenal system (SAS) by blocking β1-adrenergic receptors of the heart.
When administered once orally in patients with coronary artery disease without signs of chronic heart failure, bisoprolol reduces heart rate, reduces the stroke volume of the heart and, as a result, reduces the ejection fraction and myocardial oxygen demand. With long-term therapy, the initially elevated TPR decreases. A decrease in renin activity in blood plasma is considered as one of the components of the hypotensive effect of beta-blockers.
Pharmacokinetics
Amlodipine
Suction
Amlodipine is well absorbed after oral administration. Cmax in blood plasma is observed after 6-12 hours. Taking the drug with food does not affect its absorption. Absolute bioavailability is 64-80%.
Distribution
Apparent Vd is 21 l/kg. Css in blood plasma (5-15 ng/ml) is achieved 7-8 days after starting the drug.
In vitro studies have shown that circulating amlodipine is approximately 93-98% bound to plasma proteins.
Metabolism and excretion
Amlodipine undergoes extensive metabolism in the liver. Approximately 90% of the dose taken is converted into inactive pyridine derivatives. Approximately 10% of the dose taken is excreted unchanged in the urine. Approximately 60% of the amount of inactive metabolites is excreted by the kidneys and 20-25% through the intestines. The decrease in plasma concentration is biphasic. The final T1/2 is approximately 35-50 hours, which allows the drug to be administered once a day. The total clearance is 7 ml/min/kg (25 l/h in a patient weighing 60 kg). In elderly patients it is 19 l/h.
Pharmacokinetics in special clinical situations
In elderly patients and patients with renal failure, no significant changes in the pharmacokinetics of amlodipine were observed.
Due to decreased clearance, patients with hepatic impairment should be given lower initial doses.
Bisoprolol
Suction
Bisoprolol is almost completely (more than 90%) absorbed from the gastrointestinal tract. Its bioavailability due to low first-pass metabolism through the liver (at approximately 10%) is approximately 90% after oral administration. Food intake does not affect bioavailability. Bisoprolol exhibits linear kinetics, with its plasma concentrations being proportional to the dose taken in the range from 5 to 20 mg. Cmax in blood plasma is achieved after 2-3 hours.
Distribution
Bisoprolol is distributed quite widely. Vd is 3.5 l/kg. Plasma protein binding reaches approximately 30%.
Metabolism
Metabolized via the oxidative pathway without subsequent conjugation. All metabolites are polar (water-soluble) and are excreted by the kidneys. The main metabolites found in blood plasma and urine do not exhibit pharmacological activity. Data obtained from experiments with human liver microsomes in vitro show that bisoprolol is metabolized primarily by the CYP3A4 isoenzyme (about 95%), and the CYP2D6 isoenzyme plays only a minor role.
Removal
The clearance of bisoprolol is determined by the balance between excretion by the kidneys unchanged (about 50%) and metabolism in the liver (about 50%) to metabolites, which are also excreted by the kidneys. The total clearance is 15 l/h. T1/2 -10-12 hours.
Indications
- arterial hypertension: replacement of therapy with monocomponent drugs amlodipine and bisoprolol in the same doses.
ICD-10 codes
Dosage regimen
Tablets for oral administration. The tablets should be taken in the morning, regardless of meals, without chewing.
The recommended daily dose is 1 tablet/day of a certain dosage.
The selection and titration of the dose individually for each patient is carried out by the doctor during the prescription of monocomponent drugs containing the active substances included in the drug Concor® AM.
Treatment with Concor® AM is usually long-term therapy.
In patients with impaired liver function, the elimination of amlodipine may be slowed down. A special dosage regimen for this group of patients has not been determined, however, the drug in this case should be prescribed with caution.
For patients with severe liver dysfunction, the maximum daily dose of bisoprolol is 10 mg.
In patients with mild or moderate renal impairment, dosage regimen adjustment is usually not required. Amlodipine is not eliminated by dialysis. Patients undergoing dialysis should be prescribed amlodipine with extreme caution.
For patients with severe renal impairment (creatinine clearance less than 20 ml/min), the maximum daily dose of bisoprolol is 10 mg.
For elderly patients, the drug can be prescribed in normal doses. Caution is required only when increasing the dose.
The drug is not recommended for use in children and adolescents under the age of 18 due to the lack of data on effectiveness and safety.
Treatment should not be stopped abruptly, because this may lead to a temporary deterioration of the clinical condition. Especially treatment should not be abruptly stopped in patients with coronary artery disease. A gradual dose reduction is recommended.
Side effect
Determination of the frequency of adverse reactions observed with the separate use of amlodipine and bisoprolol: very often (≥1/10), often (≥1/100 - <.1/10), infrequently (≥1/1,000 - <.1/100) , rare (≥1/10,000 - <.1/1,000), very rare (<.1/10,000), unknown (assessment cannot be made based on available data).
Amlodipine
From the hematopoietic system: very rarely - leukopenia, thrombocytopenia.
From the immune system: very rarely - allergic reactions.
Metabolism: very rarely - hyperglycemia.
From the mental side: infrequently - insomnia, mood changes (including anxiety), depression, rarely - confusion.
From the nervous system: often - headache, dizziness, drowsiness (especially at the beginning of treatment), infrequently - fainting, hypesthesia, paresthesia, dysgeusia, tremor, very rarely - muscle hypertension, peripheral neuropathy.
From the side of the organ of vision: infrequently - visual impairment (including diplopia).
From the organ of hearing and labyrinthine disorders: infrequently - tinnitus.
From the digestive system: often - nausea, abdominal pain, infrequently - changes in bowel movements (including constipation or diarrhea), dyspepsia, dry oral mucosa, very rarely - gastritis, gum hyperplasia, pancreatitis.
From the liver and biliary tract: very rarely - hepatitis (in most cases with cholestasis), jaundice (in most cases with cholestasis).
From the cardiovascular system: often - a feeling of palpitations, flushing of the face, infrequently - a pronounced decrease in blood pressure, very rarely - myocardial infarction, arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation), vasculitis.
From the respiratory system: infrequently - shortness of breath, rhinitis, very rarely - cough.
From the urinary system: infrequently - pollakiuria, painful urge to urinate, nocturia.
From the genital organs and mammary gland: infrequently - impotence, gynecomastia.
From the musculoskeletal system: often - swelling of the ankles, infrequently - arthralgia, myalgia, muscle cramps, back pain.
Allergic reactions: very rarely - angioedema, urticaria, Quincke's edema.
From the skin and subcutaneous tissues: infrequently - alopecia, purpura, discoloration of the skin, increased sweating, itching, rash, exanthema, very rarely - exudative erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, photosensitivity.
General disorders: often - peripheral edema, increased fatigue, infrequently - chest pain, asthenia, pain, general malaise.
Laboratory and instrumental data: infrequently - increase in body weight, loss of body weight, very rarely - increase in the activity of liver enzymes in most cases with cholestasis.
Bisoprolol
From the side of metabolism: rarely - increased concentration of triglycerides.
From the mental side: infrequently - depression, rarely - hallucinations, nightmares.
From the nervous system: often - headache*, dizziness*, infrequently - insomnia, rarely - fainting.
On the part of the organ of vision: rarely - decreased lacrimation (should be taken into account when wearing contact lenses), very rarely - conjunctivitis.
From the organ of hearing and labyrinthine disorders: rarely - hearing impairment.
From the cardiovascular system: often - a feeling of coldness or numbness in the extremities, a pronounced decrease in blood pressure, infrequently - impaired AV conduction, bradycardia, worsening symptoms of chronic heart failure, orthostatic hypotension.
From the respiratory system: infrequently - bronchospasm in patients with bronchial asthma or a history of airway obstruction, rarely - allergic rhinitis.
From the digestive system: often - nausea, vomiting, diarrhea, constipation.
From the liver and biliary tract: rarely - hepatitis.
On the part of the skin and subcutaneous tissues: rarely - hypersensitivity reactions, such as itching, rash, hyperemia of the skin, very rarely - alopecia. Beta blockers may worsen the symptoms of psoriasis or cause a psoriasis-like rash.
From the musculoskeletal system: uncommon - muscle weakness, muscle cramps.
From the genital organs and mammary gland: rarely - impotence.
General disorders: often - increased fatigue*, infrequently - exhaustion*.
Laboratory and instrumental data: rarely - increased activity of liver transaminases in the blood (AST and ALT).
* These symptoms appear especially often at the beginning of the course of treatment. Typically, these phenomena are mild and usually disappear within 1-2 weeks after the start of treatment.
Contraindications for use
Amlodipine
- unstable angina (with the exception of Prinzmetal's angina),
- acute myocardial infarction (within the first 28 days),
- clinically significant aortic stenosis.
Bisoprolol
- acute heart failure or chronic heart failure in the stage of decompensation, requiring inotropic therapy,
— AV block II and III degrees, without pacemaker,
- SSSU,
- sinoatrial blockade,
- severe bradycardia (heart rate less than 60 beats/min),
- severe forms of bronchial asthma or COPD,
- severe peripheral arterial circulation disorders or Raynaud's syndrome,
- pheochromocytoma (without simultaneous use of alpha-blockers),
- metabolic acidosis.
Amlodipine/bisoprolol combination:
- severe arterial hypotension (systolic blood pressure less than 100 mm Hg),
— shock (including cardiogenic),
- age under 18 years (efficacy and safety have not been established),
- hypersensitivity to amlodipine, other dihydropyridine derivatives, bisoprolol and/or any of the excipients.
With caution: chronic heart failure (including non-ischemic etiology of functional class III-IV according to the NYHA classification), liver failure, renal failure, hyperthyroidism, diabetes mellitus with significant fluctuations in blood glucose concentration, AV block I degree, Prinzmetal's angina , occlusive diseases of peripheral arteries, psoriasis (including a history), fasting (strict diet), pheochromocytoma (with simultaneous use of alpha-blockers), bronchial asthma and COPD, concurrent desensitizing therapy, general anesthesia, old age, arterial hypotension, type 1 diabetes mellitus, aortic stenosis, mitral stenosis, acute myocardial infarction (after the first 28 days).
Use during pregnancy and breastfeeding
Amlodipine
In experimental studies, the fetotoxic and embryotoxic effects of the drug have not been established, but use during pregnancy is possible only when the benefit to the mother outweighs the potential risk to the fetus.
There is no data indicating the excretion of amlodipine in breast milk. However, it is known that other BMCA derivatives of dihydropyridine are excreted in breast milk. In this connection, if it is necessary to prescribe amlodipine during lactation, the issue of stopping breastfeeding should be resolved.
Bisoprolol
The use of bisoprolol during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus. Beta blockers reduce blood flow to the placenta and may affect fetal development.
Blood flow in the placenta and uterus should be monitored, as well as the growth and development of the unborn child should be monitored, and if adverse events occur in relation to pregnancy and/or the fetus, alternative methods of therapy should be taken.
The newborn should be carefully examined after birth. In the first three days of life, symptoms of bradycardia and hypoglycemia may occur.
There is no data on the excretion of bisoprolol in breast milk. Therefore, taking the drug is not recommended for women during breastfeeding. If taking bisoprolol during lactation is necessary, breastfeeding should be discontinued.
Use for liver dysfunction
In patients with impaired liver function, the elimination of amlodipine may be slowed down. A special dosage regimen for this group of patients has not been determined, however, the drug in this case should be prescribed with caution.
For patients with severe liver dysfunction, the maximum daily dose of bisoprolol is 10 mg.
Use for renal impairment
In patients with mild or moderate renal impairment, dosage regimen adjustment is usually not required. Amlodipine is not eliminated by dialysis. Patients undergoing dialysis should be prescribed amlodipine with extreme caution.
For patients with severe renal impairment (creatinine clearance (CC) less than 20 ml/min), the maximum daily dose of bisoprolol is 10 mg.
Use in children The drug is not recommended for use in children under 18 years of age due to the lack of data on effectiveness and safety.
Use in elderly patients Elderly patients can be prescribed the usual doses of the drug. Caution is required only when increasing the dose.
special instructions
Amlodipine
Patients with heart failure should take amlodipine with caution. In patients with heart failure stage III-IV according to the NYHA classification, amlodipine increases the risk of pulmonary edema, which is not associated with aggravation of symptoms of chronic heart failure.
Bisoprolol
Discontinuation of treatment with bisoprolol should not be sudden, especially in patients with coronary artery disease, unless there are clear indications for discontinuation of the drug. Sudden withdrawal of bisoprolol may lead to a temporary worsening of cardiac pathology.
Bisoprolol should be prescribed with extreme caution to patients with arterial hypertension or angina pectoris in combination with heart failure.
As with other beta-blockers, bisoprolol may cause increased sensitivity to allergens and increased anaphylactic reactions, so caution must be exercised when conducting concomitant desensitizing therapy. The use of adrenaline may not always give the expected therapeutic effect.
When using bisoprolol, the symptoms of hyperthyroidism may be masked.
In patients with pheochromocytoma, bisoprolol should be prescribed only after α-adrenergic receptor blockade.
Before performing general anesthesia, the anesthesiologist must be informed that the patient is taking beta-blockers. If it is necessary to discontinue a beta blocker before surgery, this should be done gradually and completed approximately 48 hours before anesthesia.
For bronchial asthma or COPD, simultaneous use of bronchodilators is indicated. In patients with bronchial asthma, there may be an increase in airway resistance, which requires a higher dose of beta2-agonists.
Impact on the ability to drive vehicles and operate machinery
During treatment with the drug, care must be taken when driving vehicles and working with technically complex mechanisms.
Overdose
Amlodipine
Symptoms: marked decrease in blood pressure with the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent arterial hypotension, including the development of shock and death).
Treatment: gastric lavage, administration of activated charcoal, maintaining the function of the cardiovascular system, monitoring indicators of heart and lung function, elevated position of the extremities, control of blood volume and diuresis. Intensive symptomatic therapy. To restore vascular tone, use vasoconstrictor drugs (in the absence of contraindications to their use), to eliminate the consequences of blockade of calcium channels - intravenous administration of calcium gluconate. Hemodialysis is not effective.
Bisoprolol
Symptoms: AV block, severe bradycardia, marked decrease in blood pressure, bronchospasm, acute heart failure and hypoglycemia. Sensitivity to a single high dose of bisoprolol varies widely among individual patients and patients with chronic heart failure are likely to be highly sensitive.
Treatment: if an overdose occurs, first of all, it is necessary to stop taking the drug and begin supportive symptomatic therapy. For severe bradycardia, intravenous administration of atropine. If the effect is insufficient, a drug with a positive chronotropic effect can be administered with caution. Sometimes temporary placement of an artificial pacemaker may be necessary.
With a pronounced decrease in blood pressure, intravenous administration of plasma-substituting solutions and vasopressor drugs. IV administration of glucagon may also be indicated.
For AV blockade, patients should be closely monitored and treated with beta-agonists such as epinephrine. If necessary, install an artificial pacemaker. In case of exacerbation of chronic heart failure, intravenous administration of diuretics, drugs with a positive inotropic effect, as well as vasodilators.
For bronchospasm - prescribing bronchodilators, incl. beta2-adrenergic agonists and/or aminophylline.
For hypoglycemia, intravenous administration of dextrose (glucose).
Bisoprolol is practically not excreted during dialysis.
Drug interactions
Amlodipine
Concomitant use of amlodipine with thiazide diuretics, beta-blockers, long-acting nitrates
