LOKREN
Active material: Betaksolol
When ATH: C07AB05
CCF: Beta1-adrenoblokator
ICD-10 codes (testimony): I10, i20
When CSF: 01.01.01.02
Manufacturer: SANOFI WINTHROP INDUSTRY (France)
DOSAGE FORM, COMPOSITION AND PACKAGING
Pills, coated, divisible, white, round, lenticular, with dividing line on one side and engraving “KE 20” – another.
| 1 tab. | |
| betaxolol hydrochloride | 20 mg |
Excipients: lactose monohydrate, sodium glikolat amylopectin, microcrystalline cellulose, Colloidal anhydrous silica, magnesium stearate, gipromelloza, macrogol 400, Titanium dioxide (E171).
14 PC. – blisters (2) – packs cardboard.
Pharmacological action
Selective beta1-blocker without intrinsic sympathomimetic activity. In high doses (at concentrations, exceeding therapeutic) has a weakly pronounced membrane stabilizing effect (like quinidine or local anesthetics).
Pharmacokinetics
Absorption
After oral administration, betaxolol quickly and completely (100%) absorbed from the gastrointestinal tract. Cmax betaxolol in blood plasma is achieved through 2-4 no. Bioavailability is about 85%.
Distribution
Binding to plasma proteins is approximately 50%. Vd is approximately 6 l / kg. Poorly penetrates the BBB and the placental barrier, slightly excreted in breast milk. Moderate fat solubility.
Metabolism
Betaxolol is metabolized in the liver to form inactive metabolites.
Deduction
Excreted by the kidneys as metabolites (more 80%), 10-15% – in unchanged form. T1/2 ʙetaksolola – 15-20 no.
Pharmacokinetics in special clinical situations
T1/2 in case of impaired liver function, it is lengthened by 33%, but the clearance does not change; with impaired renal function T1/2 doubles (dose reduction is necessary).
Not removed by hemodialysis.
Testimony
- Arterial hypertension;
- prevention of exertional angina attacks.
Dosage regimen
Average therapeutic dose is 20 mg (1 tab.) 1 time / day.
When discontinuing treatment, a gradual dose reduction is recommended for 1-2 weeks, especially in patients with coronary artery disease, to prevent the development of withdrawal syndrome (due to secondary activation of the sympathetic nervous system).
In patients with impaired renal function with CC ≥ 20 ml / min, and y patients hepatic insufficiency no correction of the daily dose of Lokren is required®. However, at the beginning of treatment, it is recommended to conduct clinical observation until equilibrium plasma concentrations of the drug are reached. (average – 4 day).
To patients with severe renal insufficiency (CC < 20 ml / min) and hemodialysis, recommended starting dose of Lokren® is 5 mg / day, regardless of the frequency and time of hemodialysis sessions.
The tablets are taken orally, not chewing and drinking plenty of fluids.
Side effect
From the central and peripheral nervous system: fatigue, weakness, dizziness, headache, drowsiness, insomnia, nightmares, depression, anxiety, confusion or short-term memory loss, hallucinations, asthenic syndrome, muscular weakness, paresthesias in extremities (for claudication, Raynaud's syndrome), tremor.
Cardio-vascular system: sinusovaya bradycardia, heartbeat, orthostatic hypotension, conduction disturbances infarction, AV блокада (up to heart failure), Arrhythmia, weakening of myocardial contractility, development (or aggravation) symptoms of heart failure (swelling of the ankles, stop, goleneй), marked reduction in blood pressure, manifestation of vasospasm (decreased peripheral circulation, coldness of the lower extremities, Raynaud's syndrome), chest pain.
From the digestive system: dryness of the mucous membranes of the mouth, nausea, vomiting, abdominal pain, constipation or diarrhea, abnormal liver function (dark urine, yellow skin or sclera, cholestasis), change in taste.
The respiratory system: nasal congestion, difficulty breathing when administered at high doses (loss of selectivity); laringo- and bronchospasm (in predisposed patients).
On the part of the organ of vision: visual impairment, decreased secretion of the lacrimal gland, dryness and soreness of eyes, conjunctivitis.
On the part of the endocrine system: hyperglycemia in patients with non-insulin dependent diabetes mellitus, hypoglycemia in patients, receiving insulin, hypothyroid state.
Dermatological reactions: increased sweating, dermahemia, rash, psoriasiform skin reactions, exacerbation of the course of psoriasis.
Allergic reactions: skin rash, itch, hives.
Other: backache, arthralgia, the weakening of the libido, reduced potency, withdrawal (increasing angina attacks, increased blood pressure); rarely – the appearance of antinuclear antibodies (only in exceptional cases is accompanied by clinical manifestations such as systemic lupus erythematosus, passing on discontinuation of treatment).
Contraindications
- chronic heart failure II B-III stage;
- Cardiogenic shock;
— AV-blockade II and III degrees (without connecting an artificial pacemaker);
- Prinzmetal angina;
- SSS (incl. sinoatrialynaya blockade);
- Vыrazhennaya bradycardia;
- Hypotension;
- Kardiomegalija (without signs of heart failure);
- simultaneous use with sultopride and floktaphenin;
- Simultaneous MAO inhibitors;
- Childhood and adolescence up 18 years (efficacy and safety have not been established);
- hypersensitivity to betaxolol.
The drug is contraindicated in congenital galactosemia, impaired glucose / galactose absorption or lactase deficiency (tk. contains lactose).
FROM caution use the drug in patients with a history of allergic reactions, with pheochromocytoma, metabolic acidosis, Obliterative diseases of peripheral vessels (intermittent claudication, Raynaud's syndrome), hepatic failure, chronic renal failure, during hemodialysis, myasthenia, depression (incl. history), the elderly, in AV-blockade I degrees, in chronic obstructive pulmonary disease (bronchial asthma, emphysema), in patients with psoriasis, in chronic heart failure, thyrotoxicosis, diabetes.
Pregnancy and lactation
IN experimental studies Animal no teratogenic action of Lokren was revealed®. So far, no teratogenic effects have been observed in humans., no congenital malformations were observed in controlled prospective studies.
Use of the drug during pregnancy is possible only in case, when the intended benefits to the mother outweighs the potential risk to the fetus.
Betaxolol is excreted to a small extent in breast milk. The child's risk of hypoglycemia or bradycardia has not been studied. If necessary, use Lokren® lactation should decide the issue of termination of breastfeeding.
Established, that betaxolol has an effect on the fetus (intrauterine growth, gipoglikemiâ, bradycardia). With the development of heart failure (decompensation) in newborn, mothers who took beta-blockers during pregnancy, hospitalized in ICU; glucagon administered is based 0.3 mg / kg; isoprenaline and dobutamine, usually in high enough doses and for a long time, which requires close supervision.
It will be appreciated, what about newborns, mothers who received beta-blockers, the effect of the latter persists for several days after birth. Although this residual effect may not have clinical implications, nevertheless, it is possible to develop a heart defect, a neonate requiring intensive care. In such a situation, the introduction of solutions should be avoided., increasing BCC (risk of developing acute pulmonary edema). There are also reports of bradycardia, respiratory distress syndrome and hypoglycemia. Therefore, careful monitoring of newborns in specialized settings is recommended. (control of heart rate and blood glucose levels during the first 3-5 days of life).
Cautions
Treatment for angina patients should never be interrupted abruptly., sudden cancellation can lead to severe heart rhythm disturbances, myocardial infarction or sudden death.
Patients, host Lokren®, monitoring required, which should include monitoring heart rate and blood pressure (at the beginning of treatment daily, then 1 once every 3-4 Months), glucose content in diabetic patients (1 once every 4-5 Months), monitoring of renal function is necessary in elderly patients (1 once every 4-5 Months). It should teach the patient methods of calculating heart rate and instruct on the need of medical advice in heart rate less than 50 u. / min.
In patients with coronary artery disease, the dose should be reduced gradually. (during 1-2 weeks) and, if necessary, start substitution therapy at the same time, to avoid progression of angina pectoris. Approximately 20% patients with angina Beta-blockers are ineffective (the main reasons for – severe coronary atherosclerosis with a low threshold of ischemia and heart rate at the time of the development of an anginal attack less 100 bpm and increased left ventricular end-diastolic pressure, disrupting subendocardial blood flow).
With simultaneous therapy with clonidine, its intake can be discontinued only a few days after Lokren's cancellation®.
Lokren® should repeal before the study content in the blood and urine Catecholamines, normetanefrina, vanilinmindalnoy acid, antinuclear antibodies.
In bronchial asthma and chronic obstructive pulmonary disease, beta-blockers can be prescribed only for moderate disease, with the choice of a selective beta-blocker at a low initial dose. Respiratory function assessment is recommended before starting treatment.. If seizures develop during treatment, bronchodilators can be used. (beta2-adrenomimetiki).
In patients with heart failure, controlled therapeutically, if necessary, betaxolol can be used in very low, gradually increasing doses under strict medical supervision.
The dose of the drug must be reduced, if the resting heart rate is lower 50-55 beats / min and the patient has clinical manifestations of bradycardia.
Given the negative dromotropic effect of beta-blockers, in case of AV blockade of I degree, the drug should be used with caution.
Beta-blockers can increase the number and duration of attacks in Prinzmetal's angina. Use of cardioselective beta1-adrenergic blockers is possible with less severe and mixed forms, provided, that the treatment is carried out in combination with vasodilators.
Beta-blockers can worsen the condition of patients with peripheral circulatory disorders (Raynaud's disease or syndrome, arteritis or chronic obliterating diseases of the arteries of the lower extremities).
When using beta-blockers for the treatment of arterial hypertension, caused by pheochromocytoma, requires careful monitoring of blood pressure.
Patients with diabetes mellitus should be warned about the need to strengthen self-monitoring of blood glucose levels at the beginning of treatment. Initial symptoms of hypoglycemia can be masked, especially the tachycardia, palpitations and sweating.
In psoriasis, a careful assessment of the need for drug administration is required, tk. there are reports of a worsening of the course of the disease during treatment with beta-blockers.
In patients with a tendency to severe anaphylactic reactions (especially associated with the use of floctaphenin or during desensitization) therapy with beta-blockers can lead to further intensification of reactions and a decrease in the effectiveness of treatment. When using the drug, the risk of developing anaphylactic reactions should be taken into account..
When performing general anesthesia, consider, that beta-blockers mask reflex tachycardia and increase the risk of developing arterial hypotension. Continuation of beta-blocker therapy reduces the risk of arrhythmia, myocardial ischemia and hypertensive crises. The anesthesiologist should be advised that, that the patient was being treated with beta-blockers.
With a planned surgical operation and the need to discontinue drug therapy, it should be taken into account, that drug withdrawal for 48 h allows you to restore sensitivity to catecholamines. Beta-blocker therapy should not be interrupted in patients with coronary insufficiency, it is recommended to continue treatment until surgery, considering the risk, associated with sudden withdrawal of beta-blockers. For emergency operations or in those cases, when stopping treatment is not possible, the patient should be protected from the consequences of excitation of the vagus nerve by appropriate premedication with atropine (with repetition if necessary). For general anesthesia, it is necessary to use drugs with a minimal negative inotropic effect..
Symptoms of thyrotoxicosis can be masked with beta-blocker therapy.
Athletes should consider, that the drug may react positively during doping control tests.
When using the drug, you should exclude the use of alcohol.
Sick, use contact lenses, We should take into account, that during treatment, it is possible to reduce the lacrimal fluid.
If tobacco use effectiveness of beta-blockers lower.
Treatment of elderly patients should be started with a low dose and under close supervision..
In patients with renal insufficiency, the dose must be adjusted depending on the concentration of creatinine in the blood or CC.
Use in Pediatrics
The drug should not be used in children., tk. there are no clinical data on the efficacy and safety of its use in this category of patients.
Overdose
Symptoms: vыrazhennaya bradycardia, dizziness, AV блокада, marked reduction in blood pressure, Arrhythmia, ventricular premature beats, insensibility, heart failure, difficulty breathing, bronchospasm, cyanosis of fingernails and palms, convulsions.
Treatment: gastric lavage, appointment of adsorbents; with bradycardia or an excessive decrease in blood pressure, intravenous administration of atropine in a dose is recommended 1-2 mg; 1 mg glucagon repeated as needed; at the same time, if necessary, give a slow infusion 25 mcg of isoprenaline or dobutamine in a dose 2.5-10 ug / kg / min.
Drug Interactions
Many drugs can cause bradycardia. This group includes beta-blockers, class IA antiarrhythmic drugs (quinidine, disopyramide), amiodarone and sotalol from class III antiarrhythmic drugs, diltiazem and verapamil from class IV, as well as foxglove glycosides, klonidin, guanfaцin, mefloquine and cholinesterase inhibitors, indicated for the treatment of Alzheimer's disease.
Contraindicated in combination
With simultaneous use with floktaphenin (in case of shock or arterial hypotension, caused by floctaphenin) beta-blockers can lead to a decrease in compensatory reactions from the cardiovascular system.
With simultaneous use with sultopride, severe bradycardia develops (additive effect).
Combinations, which should be avoided
When used simultaneously with calcium channel blockers (bepridil, diltiazem and verapamil) violations of automatism occur (vыrazhennaya bradycardia, Stop sinus), violations AV conduction, heart failure (synergism). This combination can only be used under close clinical supervision and ECG control. (especially in the elderly or at the beginning of therapy).
With simultaneous use with amiodarone, contractility disorders may develop, automaticity and conductivity (suppression of sympathetic compensatory mechanisms).
Combinations, which should be used with caution
When using halogenated inhalation agents for general anesthesia, consider, that during the operation the effect of blocking β-adrenergic receptors can be eliminated by beta-adrenostimulants. Usually, beta-blocker therapy should not be discontinued, and abrupt withdrawal of the drug should be avoided in any case. The anesthesiologist must be informed about the treatment.
When used simultaneously with Lokren® class IA antiarrhythmic drugs (quinidine, hydroquinidine and disopyramide) and class III (Amiodarone, dofetilid, iʙutilid, sotalol), some antipsychotics from the phenothiazine group (chlorpromazine, ciamemazin, levomepromazin, tioridazin), benzamides (amisulpride, sulьpirid, tiapride), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozid), as well as cisapride, difemanila, Erythromycin (for / in the), halofantrine, misolastin, moxifloxacin, pentamidine, spiramycin (for / in the) and vincamine (for / in the) possible increased risk of ventricular arrhythmia, especially type “pirouette” (if a combination therapy is required, clinical monitoring and ECG monitoring are required).
With simultaneous use with propafenone, the development of contractility disorders is possible, automaticity and conductivity (by suppressing sympathetic compensatory mechanisms), which requires monitoring of the clinical condition and ECG.
When used together with baclofen, an increase in the antihypertensive effect is possible (need blood pressure control and dose adjustment if necessary).
When combined with insulin and oral hypoglycemic agents, sulfonylurea derivatives should be considered, that all beta-blockers can mask the symptoms of hypoglycemia (palpitations and tachycardia). The patient should be warned about the need to enhance blood glucose control, especially at the beginning of treatment.
With simultaneous use with cholinesterase inhibitors (donepezil, galantamin, ambenonium chloride, neostigmine, pyridostigmine, rivastigmine, tacrine) possible increased risk of developing bradycardia (additive effect), which requires monitoring of the clinical condition.
When combined with antihypertensive drugs of central action (klonidin, apraclonidine, alpha-methyldopa, guanfaцin, moksonidin, rilmenidine) a significant increase in blood pressure is possible with a sharp cancellation of a centrally acting antihypertensive drug (it is necessary to avoid abrupt withdrawal of the antihypertensive drug and monitor the clinical condition).
With intravenous administration of lidocaine, it is possible to increase the concentration of lidocaine in the blood plasma with a possible increase in unwanted neurological symptoms and effects on the part of the cardiovascular system (decreased metabolism of lidocaine in the liver), which requires monitoring of the clinical condition and ECG and, perhaps, monitoring the concentration of lidocaine in blood plasma during treatment with beta-blockers and after its termination. If necessary, – dose adjustment of lidocaine.
Combinations, that should be taken into account
When used simultaneously with NSAIDs for systemic use (incl. selective COX-2 inhibitors) a decrease in the hypotensive effect is possible (inhibition of prostaglandin synthesis and water and sodium retention).
With simultaneous use with calcium channel blockers, the development of arterial hypotension is possible., circulatory failure in patients with latent or uncontrolled heart failure. Beta-blocker therapy may minimize reflex sympathetic mechanisms.
In a joint application with tricyclic antidepressants (imipramine type), neuroleptics may increase the hypotensive effect and increased risk of orthostatic hypotension (additive effect).
While the use of mefloquine increased risk of bradycardia (additive effect).
When combined with dipyridamole (for / in the) may increase the antihypertensive effect.
When concomitant administration with alpha-blockers, used in urology (alьfuzozin, doksazozin, prazosin, tamsulozin, terazosin), increased antihypertensive effect and increased risk of orthostatic hypotension.
When combined with amifostine, an increase in the antihypertensive effect is possible.
Allergens, used for immunotherapy, or allergen extracts for skin samples, increase the risk of severe systemic allergic reactions or anaphylaxis in patients, receiving betaxolol.
When administered intravenously, phenytoin increases the severity of the cardiodepressant effect and the likelihood of lowering blood pressure in patients, taking betaxolol.
When used together, betaxolol reduces the clearance of xanthines (except difillina) and increases their concentration in blood plasma, especially in patients with initially increased clearance of theophylline (eg, under the influence of smoking).
The antihypertensive effect of betaxolol is weakened by estrogens (sodium retention).
When combined with betaxolol, cardiac glycosides, methyldopa, reserpine and guanfacine increase the risk of developing or worsening bradycardia, AV-blockade, cardiac arrest.
When combined with betaxolol, nifedipine, Diuretic, klonidin, simpatolitiki, hydralazine and other antihypertensive drugs can lead to a significant decrease in blood pressure.
When used together, betaxolol lengthens the duration of action of non-depolarizing muscle relaxants and enhances the anticoagulant effect of coumarins.
When combined with betaxolol ethanol, sedatives and hypnotics drugs increase CNS depression.
Not recommended simultaneous application with MAO inhibitors due to a significant increase in the hypotensive action, the break in treatment between taking MAO inhibitors and betaxolol should be at least 14 days.
When combined with betaxolol, unhydrogenated ergot alkaloids increase the risk of developing peripheral circulatory disorders.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
The drug should be stored out of reach of children at or below 25 ° C. Shelf life – 5 years.
