Selegiline - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Dopaminomimetics

Included in the formulation

Yumex®

pills inwards

HINOIN Pharmaceutical and Chemical Products Plant, ZAO Hungary

АТХ:

N.04.B.D Inhibitors of monoamine oxidase type B

Pharmacodynamics:

Inhibiting MAO-B, reduces the destruction of dopamine in neurons of black substance and potentiates the action of levodopa, which allows to reduce the dose of levodopa by an average of 30%.

When administered at a dose of 10 mg / day causes complete suppression of MAO-B in the central nervous system, at a dose of 20-40 mg / day - nonselective inhibition of all types of MAO.

Inhibition of reverse neuronal uptake of dopamine.

Has a neuroprotective effect, delaying the destruction of dopaminergic neurons of the brain.

This effect is explained by the fact that, suppressing the oxidative metabolism of dopamine, the drug reduces the formation of free oxygen radicals that cause the death of dopaminergic neurons.

Pharmacokinetics:

Absorption is high. It penetrates well through the BBB. Relationship with plasma proteins 94%. Biotransformation occurs in the liver to N-desmethyldeprenil in the liver (half-life of 2 h), amphetamine (half-life of 17.7 h) and methamphetamine (half-life of 20.5 h). The duration of action depends on the regeneration of MAO-B. Elimination is mainly kidney and feces (about 15%).

Indications:

Parkinson's disease, symptomatic parkinsonism.In combination with levodopa, as monotherapy in the early stages.

ICD-10

VI.G20-G26.G22 * Parkinsonism in diseases classified elsewhere

VI.G20-G26.G21.9 Secondary Parkinsonism, unspecified

VI.G20-G26.G21.8 Other forms of secondary parkinsonism

VI.G20-G26.G21.3 Postencephalitic parkinsonism

VI.G20-G26.G21.2 Secondary Parkinsonism, caused by other external factors

VI.G20-G26.G21.1 Other forms of secondary parkinsonism caused by drugs

VI.G20-G26.G21 Secondary Parkinsonism

VI.G20-G26.G20 Parkinson's disease

Contraindications:

Hypersensitivity, extrapyramidal disorders not associated with dopamine deficiency (essential tremor, Huntington's chorea); pregnancy, breast-feeding.

Carefully:

Peptic ulcer disease of the stomach and duodenum, uncontrolled arterial hypertension, severe forms of angina pectoris, psychosis, glaucoma, thyrotoxicosis, pheochromocytoma, prostatic hyperplasia (with the presence of residual urine), age to 18 years.

Pregnancy and lactation:

Category of recommendations FDA C.

Contraindicated in pregnancy and lactation.

Dosing and Administration:

Inside, 10 mg / day in 2 divided doses for 5 mg at breakfast and at lunch.As a rule, it is used together with combinations of levodopa / carbidopa. During prolonged therapy, a dose of levodopa may be reduced.

Side effects:

From the nervous system and sensory organs: anxiety, fatigue, dizziness, headache, drowsiness or insomnia, depression, hallucinations, confusion, speech disorders, gait, supraorbital pain, visual acuity, diplopia.

From the cardiovascular system and blood (hematopoiesis, hemostasis): arrhythmia, orthostatic reactions, increased blood pressure, swelling.

On the part of the intestine: nausea and vomiting, decreased appetite, dry mouth, indigestion, constipation or diarrhea, exacerbation of peptic ulcer, increased activity of hepatic transaminases.

Other: disorders of sexual function, urinary retention, exacerbation of bronchial asthma, dysuria, hyperhidrosis, photosensitivity, skin rash.

Overdose:

Symptoms: it is possible to develop a "cheese" syndrome (inhibits all types of MAO) in the form of hypertensive reactions and exacerbation of IHD after ingestion of food containing tyramine (cheese, coffee, etc.), stimulation.

Treatment: induction of vomiting, gastric lavage, the use of activated charcoal; with excitation and convulsions in / in the introduction of diazepam; symptomatic therapy.

Interaction:

Selegilin enhances the effects of levodopa.

Because the selegiline potentiates the action of levodopa, side effects of levodopa can be intensified, especially when using high doses of levodopa. The use of selegiline in the treatment of levodopa can cause involuntary movements and / or agitation in patients. In such cases, strict monitoring of the patients' condition is necessary. These side effects disappear when the dose of levodopa decreases. With the simultaneous use of selegiline and levodopa, the dose of levodopa can be reduced by an average of 30%.

Against the background of altretamine can cause orthostatic hypotension.

Increases the risk of side effects of amantadine.

When combined with amisulpride, there is a mutual antagonism of the dopaminergic receptor agonist and neuroleptic. Selegiline can cause or exacerbate psychotic symptoms. Amisulpride may enhance symptoms of Parkinson's disease (combination not recommended).

Strengthens (mutually) the effects of amitriptyline, incl. probability of development and severity of side effects; simultaneous and / or consistent use (not recommended) can lead to behavioral changesand mental status, hypertension, fainting, asystole, muscle stiffness, bouts of sweating, hyperpyrexia and even death.

The effects of atenolol may be unpredictable; joint application is not recommended.

In vitro data showed inhibition of betahistine metabolism by selegiline. Caution should be exercised while concomitant administration of betagistine and selegiline.

Using bupivacaine increases the risk of excessive blood pressure lowering.

Combined use is contraindicated with buprenorphine: stupor development, muscle stiffness, agitation, hallucinations, hyperpyrexia, and can lead to respiratory depression, coma, convulsions and death.

The increase in blood pressure and the emergence of hypertensive crisis after simultaneous application of buspirone and selegiline are described, therefore these preparations can not be combined. After the abolition of selegiline before the application of buspirone (and vice versa) should take at least 14 days.

Against the background of venlafaxine provokes the development of adverse reactions, incl. heavy; joint and / or consistent use is contraindicated.

Combination guaifenesin + dextromethorphan It is incompatible with selegiline, which, if used at the same time, can cause adrenergic crisis, collapse, coma, dizziness, agitation, increased blood pressure, hyperpyrexia, intracranial bleeding, drowsiness, nausea, spasms, tremor.

Selegiline weakens the effect of glipizide. When combined, dose adjustment may be required.

Simultaneous application with combination dextromethorphan + paracetamol can cause adrenergic crisis, collapse, coma, dizziness, agitation, increased blood pressure, hyperpyrexia, intracranial hemorrhage, lethargy, nausea, spasms, tremor. Reception combination dextromethorphan + paracetamol It is desirable to exclude seleghiline for the time of taking selegiline due to the presence of dextromethorphan in its composition.

When used simultaneously with dextromethorphan (in combination dextromethorphan + phenylephrine + chlorphenamine) can cause adrenergic crisis, collapse, coma, dizziness, agitation, increased blood pressure, hyperpyrexia, intracranial hemorrhage, lethargy, nausea, spasms, tremor.

Selegilin, when combined, enhances the pressor effect and arrhythmogenicity of phenylephrine (in combination dextromethorphan + phenylephrine + chlorphenamine).

Selegilin prolongs and intensifies the anticholinergic effects of diphenhydramine.

Strengthens (mutually) the therapeutic and side effects of imipramine; joint or sequential appointment is not recommended, as it can cause changes in behavioral and mental status, bouts of sweating, muscle rigidity, hypertension, fainting, asystole.

Increases the risk of development and severity of side effects of carbamazepine; joint appointment is contraindicated.

Strengthens the action of carvedilol on AD (hypotension) and heart rate (bradycardia).

Potentiation of CNS oppression by clonazepam.

Large doses of caffeine (in combination caffeine + paracetamol + propyphenazone or caffeine + ergotamine) with a combined application can cause dangerous cardiac arrhythmias or a marked increase in blood pressure.

The use of lidocaine, mepivacaine (in combination mepivacaine + epinephrine) with selegilin increases the risk of lowering blood pressure.

Selegilin inhibits MAO and can unpredictably enhance the effect of methyldopa; joint use is contraindicated.

Selegilin increases the duration of circulation of catecholamines released by metoclopramide; Care should be taken when concomitant administration, especially for patients with essential hypertension.

It unpredictably intensifies the effect of mianserin: severe, sometimes fatal reactions, including hyperthermia, rigidity, myoclonus, vegetative disorders, extreme excitement, progressing to delirium and to whom; combined use is excluded.

Contraindicated simultaneous use of moclobemide and selegiline.

Against the background of morphine, fever and toxic effects on the central nervous system are possible.

The combined use of selegiline and paroxetine is contraindicated, including a period of up to 5 weeks. after the withdrawal of paroxetine.

Against paroxetine, pyrlinole selegiline can cause severe, sometimes fatal reactions, including hyperthermia, rigidity, myoclonus, autonomic disorders, extreme excitement, progressing to delirium and to whom; joint use is contraindicated.

Simultaneous use of procaine with selegiline (inhibits MAO) increases the risk of developing hypotension.

Selegilin increases the likelihood of developing extrapyramidal disorders with prometazine.

Selegilin enhances the hypoglycemic effect of repanglide.

Selegilin enhances the effect on the SSS of salmeterol.

The combined use of selegiline and sertraline is contraindicated, this can cause severe, sometimes fatal reactions, including hyperthermia, rigidity, myoclonus, autonomic disorders, extreme excitement, progressing to delirium and to whom; joint and / or consistent use is contraindicated.

May increase (mutually) the risk of developing side effects of sumatriptan; joint use is contraindicated.

In the presence of terbinafine inhibits (shown in vitro) CYP2D6, as a result, biotransformation may be slowed down and the plasma level may increase.

Selegilin enhances the effect on terbutaline CAS; A simultaneous and / or consistent use must be made with extreme caution.

When using tetracaine (in combination tetracaine + chlorhexidine in the form of a spray for topical application) with selegilin increases the risk of lowering blood pressure.

With tramadol and fluvoxamine may cause serotonin syndrome (fever, agitation, tremor and anxiety, convulsive attacks).

Selegilin enhances the pressor effect of phenylephrine.

Selegilin enhances (mutually) the effect and risk of toxic manifestations of fentanyl (stupor, muscle stiffness, agitation, hallucinations, hyperpyrexia, etc.); combined use is contraindicated.

Selegiline should not be used together with fluoxetine - a serotonin reuptake inhibitor, may develop excitation, hypertension, convulsions, ataxia, hallucinations and manic psychosis, and fluoxetine Do not use within 14 days after the abolition of selegiline. As fluoxetine has a very long half-life, after the elimination of fluoxetine and before the appointment of selegiline should be at least 5 weeks.

Special instructions:

With caution appoint with kidney failure, pathology of the cardiovascular system, peptic ulcer of the stomach and duodenum, glaucoma, diseases of the thyroid gland and adrenal glands.

Reduces the speed of reaction and attention, it is necessary to inform drivers of vehicles and working with potentially dangerous mechanisms.

Consider the long-term aftereffect of the drug against MAO - up to 5-7 days with the appointment of adrenomimetics. Selegiline can be administered 5 weeks after fluoxetine cancellation.

Instructions

Selegiline (Selegilinum)