Levodopa+Benserazide, 200 mg+50 mg capsules 100 pcs

Levodopa, Benserazid

Indications

Parkinson’s disease Treatment of all forms of Parkinson’s disease except drug-induced parkinsonism.

Restless legs syndrome

Levodopa + Benserazide is indicated for the treatment of restless legs syndrome, including:
idiopathic restless legs syndrome;
“restless legs” syndrome in patients with chronic renal failure on dialysis.

Pharmacological effect

Pharmacotherapeutic group: Antiparkinsonian drug (dopamine precursor + peripheral decarboxylase inhibitor)

Pharmacological action

Levodopa/benserazide is a combination antiparkinsonian drug containing a dopamine precursor and an inhibitor of peripheral aromatic L-amino acid decarboxylase. In Parkinsonism, the neurotransmitter dopamine is produced in the basal ganglia in insufficient quantities. Replacement therapy is carried out through the use of levodopa, a direct metabolic precursor of dopamine.

Most of levodopa is converted to dopamine in peripheral tissues (intestines, liver, kidneys, heart, stomach), which is not involved in the antiparkinsonian effect, since peripheral dopamine penetrates the BBB poorly and is also responsible for most of its adverse reactions. Blocking extracerebral decarboxylation of levodopa is highly desirable.

This is achieved by the simultaneous administration of levodopa and benserazide, an inhibitor of peripheral aromatic L-amino acid decarboxylase, which reduces the formation of dopamine in peripheral tissues, which indirectly leads to an increase in the amount of levodopa entering the central nervous system, on the one hand, and to a decrease in the manifestations of undesirable reactions of levodopa, on the other. A combination of these substances in a 4:1 ratio is as effective as high-dose levodopa.

Pharmacokinetics

Absorption occurs mainly in the upper parts of the small intestine. The time to reach Cmax of levodopa in plasma is 1 hour. Cmax in plasma and the degree of absorption increase in proportion to the dose.

Eating reduces the rate and extent of absorption.

Levodopa crosses the BBB via a saturable transport system and does not bind to plasma proteins.

Benserazide in therapeutic doses does not penetrate the BBB and accumulates mainly in the kidneys, lungs, small intestine and liver.

T1/2 of the main metabolite from plasma is 15-17 hours, and in patients taking therapeutic doses of the drug, its accumulation occurs.

T1/2 of levodopa is 1.5 hours. Plasma clearance of levodopa is approximately 430 ml/min.

Benserazide is almost completely eliminated by metabolism. Metabolites are excreted primarily in urine and, to a lesser extent, in feces.

Special instructions

Sudden discontinuation of levodopa is unacceptable; Abrupt withdrawal may lead to the development of NMS.

Patients with open-angle glaucoma should regularly monitor intraocular pressure during treatment.

During the treatment period, monitoring of liver and kidney function and peripheral blood count is necessary.

In patients with a history of myocardial infarction, coronary artery disease, or arrhythmia, cardiac function should be regularly assessed (particularly with an ECG).

The drug should not be used in patients with malignant melanoma (including in the case of a suspected diagnosis, the presence of undiagnosed skin lesions or a history of malignant melanoma).

In patients with diabetes mellitus, frequent monitoring of plasma glucose concentrations and, if necessary, dose adjustment of hypoglycemic drugs are necessary.

Treatment is carried out until surgery, requiring general anesthesia (with the exception of the use of halothane).

Treatment with the combination of levodopa + benserazide may affect the laboratory results of catecholamines, creatinine, uric acid and glucose; a false-positive Coombs test is possible.

Some patients taking dopamine receptor agonists have reported cases of pathological gambling, increased libido and hypersexuality.

Some patients with Parkinson’s disease have experienced behavioral and cognitive disorders as a result of uncontrolled use of increasing doses of the drug.

Impact on the ability to drive vehicles and machinery.

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions; If episodes of drowsiness occur, you should stop driving.

Active ingredient

Levodopa, [Benserazide]

Composition

Active ingredients:

Levodopa 200 mg
benserazide hydrochloride 57 mg

which corresponds to the content of benserazide 50 mg

Excipients: sodium lauryl sulfate – 1 mg, microcrystalline cellulose – 64 mg, calcium hydrogen phosphate – 150 mg, colloidal silicon dioxide – 15 mg, crospovidone – 10 mg, magnesium stearate – 3 mg.

Pregnancy

The drug Levodopa + Benserazide is absolutely contraindicated during pregnancy and in women of childbearing age who do not use reliable methods of contraception, due to possible disruption of skeletal development in the fetus. If pregnancy occurs during treatment, the drug should be discontinued in accordance with the recommendations of the attending physician.

If it is necessary to take the drug Levodopa + Benserazide during breastfeeding, breastfeeding should be discontinued due to the lack of reliable data on the penetration of benserazide into breast milk. The risk of abnormal skeletal development in a newborn cannot be ruled out.

Contraindications

Hypersensitivity to levodopa, benserazide or any other auxiliary component of the drug. Decompensated dysfunction of the endocrine organs, liver or kidneys (except for patients with restless legs syndrome receiving dialysis), diseases of the cardiovascular system in the stage of decompensation, mental illness with a psychotic component, angle-closure glaucoma.

Levodopa + Benserazide should not be used in combination with non-selective monoamine oxidase inhibitors (MAO) or in combination with MAO-A and 4 107758 MAO-B inhibitors.

Age under 25 years.

Pregnancy and breastfeeding period. The drug is contraindicated in women of childbearing age who do not use reliable methods of contraception.

Side Effects

From the digestive system: anorexia, nausea, vomiting, diarrhea, loss or change in taste, dryness of the oral mucosa.

From the skin: itching, rash.

From the urinary system: there may be a slight change in the color of urine (as a rule, it acquires a red tint and darkens when standing.

From the cardiovascular system: arrhythmia, orthostatic hypotension (weakens after dose reduction), increased blood pressure.

From the hematopoietic system: hemolytic anemia, transient leukopenia, thrombocytopenia, reduction in thromboplastin time.

From the nervous system: headache, dizziness, in later stages of treatment – spontaneous movements (chorea, athetosis), episodes of “freezing”, weakening of the effect towards the end of the dose, the “on-off” phenomenon, severe drowsiness, episodes of sudden drowsiness, increased symptoms of “restless legs” syndrome, agitation, anxiety, insomnia, hallucinations, delirium, temporary disorientation, depression.

From the respiratory system: rhinitis, bronchitis.

From the laboratory parameters: transient increase in the activity of “liver” transaminases and alkaline phosphatase, increase in blood urea nitrogen. There may be discoloration or staining of body fluids or tissues, particularly saliva, tongue, teeth, or oral mucosa.

Other: febrile infection.

Interaction

When levodopa is used simultaneously with antipsychotics (neuroleptics) derivatives of butyrophenone, diphenylbutylpiperidine, thioxanthene, phenothiazine, pyridoxine, the antiparkinsonian effect may be inhibited.

Antacids reduce the absorption of levodopa by 32%.

With simultaneous use of levodopa with beta-agonists, cardiac arrhythmias may occur.

With simultaneous use of levodopa with MAO inhibitors (except for MAO type B inhibitors), circulatory disorders are possible. This is due to the accumulation of dopamine and norepinephrine under the influence of levodopa, the inactivation of which is slowed down by the influence of MAO inhibitors.

With simultaneous use of levodopa with m-anticholinergic blockers, the antiparkinsonian effect may be reduced; with anesthesia – the risk of developing arrhythmia.

Ferrous sulfate reduces the maximum plasma concentrations and AUC of levodopa by 30-50%, which is a clinically significant change in some but not all patients.

There is evidence of a decrease in the bioavailability of levodopa with simultaneous use of tricyclic antidepressants.

With simultaneous use of levodopa with diazepam, clozepine, methionine, clonidine, phenytoin, the antiparkinsonian effect may be reduced.

Sympathomimetics (adrenaline, norepinephrine, isoproterenol, amphetamine). Should not be taken simultaneously as levodopa may potentiate their effects.

When levodopa is used simultaneously with lithium salts, the risk of developing dyskinesias and hallucinations may increase.

With simultaneous use of levodopa with papaverine hydrochloride, reserpine, a significant decrease in the antiparkinsonian effect is possible; with suxamethonium – arrhythmias are possible; with tubocurarine – increased risk of developing arterial hypotension.

When using levodopa in combination with benserazide, along with a decrease in a number of side effects from the nervous system and cardiovascular system, there may be a tendency to the early development of dyskinesia and mental disorders, which is associated with the action of levodopa.

Overdose

Symptoms mentioned in the section, but in a more pronounced form: from the cardiovascular system (arrhythmias), mental health (confusion, insomnia), from the gastrointestinal tract (nausea and vomiting), pathological involuntary movements.

Therapy: vital functions must be monitored.

Symptomatic therapy: respiratory analeptics, antiarrhythmics, and, in appropriate cases, neuroleptics.

Manufacturer

Izvarino Pharma, Russia