Left lump ретард

General characteristics. Structure:

Active agents: levodopas of 200 mg, karbidopa of 50 mg;

Excipients: коповидон, a gidroksipropilmetiltselyuloza, calcium гидрогенфосфат a dihydrate, Mannitolum, cellulose microcrystallic, silicon dioxide colloid anhydrous, the sodium stearylfumarating magnesium stearate, a covering for drawing a cover of Opadry II Orange.

Pharmacological properties:

Pharmacodynamics. The left lump ретард represents a combination of inhibitor of a decarboxylase of a karbidopa and the metabolic predecessor of dopamine of a levodopa in the form of tablets of the prolonged action on a polymeric basis.
The left lump ретард is especially shown for reduction of the period of block at the patients who were earlier treated by a usual combination of a levodopa with decarboxylase inhibitor with displays of dyskinesia and motive fluctuations.
The levodopa gets through a blood-brain barrier and in a brain is decarboxylized in the dopamine which is effectively influencing symptoms of a disease of Parkinson. Karbidopa through a blood-brain barrier does not get and therefore inhibits ekstratserebralny decarboxylation of a levodopa. Thereof a large number of a levodopa gets into a brain and turns into dopamine. The last allows to avoid reception of high doses of a levodopa through short intervals. At the same time improvement of a clinical state is quicker observed and at the same time the gastrointestinal and cardiovascular side effects connected with increase in level of ekstratserebralny dopamine decrease.

Pharmacokinetics. The pharmacokinetics of tablets of the prolonged action was studied at patients with Parkinson's disease.
Absorption of a levodopa after use of a levodopa / карбидопы 200/50 mg with slow release continues more than 4 - 6 h. Thanks to it fluctuations of concentration of a levodopa in plasma are noted in narrower framework, than at use of tablets of a levodopa / карбидопы with bystry release.
Bioavailability of a levodopa makes about 70% in comparison with tablets with bystry release of the tablets of the prolonged action (containing in the structure a levodopa / карбидопу). Because of it the daily dose of a levodopa in levodopa tablets / карбидопы has to be higher than the prolonged action, than in tablets with bystry release.
The average time of achievement of the maximum concentration in plasma for tablets of the prolonged action of 200/50 mg makes nearly 2 h.
Reception of food does not influence absorption of a levodopa, however reduces bioavailability of a karbidopa by 50%, and the maximum concentration in plasma – for 40%. At the same time decrease in levels of a karbidopa in plasma has no clinical value.
In the presence of a karbidopa the levodopa is metabolized to amino acids and, to a lesser extent, to derivative catecholamines. All metabolites are removed by kidneys.

Indications to use:

Treatment of an idiopathic disease of Parkinson, symptomatic parkinsonism.

Route of administration and doses:

Tablets of the prolonged action can be divided, but it is not necessary to chew to keep properties of drug.

The optimum daily dose of drug should be selected carefully for each patient. In the course of selection of a dose behind a condition of the patient constant control has to be established, especially at emergence or strengthening of such manifestations owing to drug use as nausea and the pathological spontaneous movements, in particular, dyskinesia, a chorea or dystonia. The nictitating spasm can be early manifestation of overdose.

Patients who were not treated by levodopa drugs earlier.

The recommended initial dose makes 1 tablet of the prolonged action   2 - 3 times a day and should not exceed 3 tablets (600 mg of a levodopa) a day. Between receptions of separate doses there have to pass not less than 6 h. Selection of a dose is carried out with an interval of not less than 2 - 4 days. Depending on disease severity the optimum therapeutic effect can be reached within 6 months of treatment.

Recommendations of rather dose mode at the patients receiving levodopa drugs with decarboxylase inhibitor with bystry release.

Between the last reception of a levodopa + inhibitor of a decarboxylase and the first reception of Levokom ретард there have to pass not less than 12 h.

Transfer into Levokom's reception ретард has to happen in the doses allowing to raise a daily dose of a levodopa no more than for 10% though there can be a need of exceeding of a daily dose of a levodopa in comparison with the previous therapy for 30%.

Time interval between receptions of separate doses should be increased to 4 - 12 h. If the daily dose is divided into unequal single doses, reception of the minimum single dose at the end of the day is recommended.

Recommendations concerning transfer of patients from levodopa tablets / карбидопы with bystry release on tablets "Levok ретард" the prolonged action are provided in the table:

Levodopa tablets / карбидопы with bystry release	Left lump ретард 200/50 mg, tablets of the prolonged action
Daily dose of a levodopa (mg)	Daily dose of a levodopa (mg)	Quantity of tablets of the prolonged action in day
100-200	200	1/2 tablets twice a day
300-400	400	1 tablet twice a day
500-600	600	1 tablet three times a day
700-800	800	4 tablets divided on 3 or more receptions
900-1000	1000	5 tablets divided on 3 or more receptions
1100-1200	1200	6 tablets divided on  3 or more receptions
1300-1 400	1400	7 tablets divided on 3 or more receptions
1500-1600	1600	8 tablets divided on 3 or more receptions

The patients receiving monotherapy by a levodopa (without decarboxylase inhibitor).
Between the last reception of a levodopa and the first reception of Levokom ретард there have to pass not less than 12 h.

At patients with easy and moderate weight of a course of a disease the recommended initial dose makes 1 tablet of Levokom ретард 200/50 mg twice a day.

Selection of a dose.
After definition of the dose mode the dose or frequency of reception can be increased depending on reaction of the patient. Correction of a dose is carried out, raising a daily dose on ½ tablets of Levokom ретард 200 mg / 50 mg each 2-3 days to achievement of optimum effect.

The maximum daily dose can make to 8 tablets of Levokom ретард 200/50 mg. In comparison with levodopa tablets / карбидопы with bystry release the effect of the first dose accepted in the morning can be delayed at some patients for an hour.

Maintenance dose.
As displays of a disease of Parkinson during treatment can change, regular routine assessment of a condition of patients is recommended. At the same time drug dose adjustment can be necessary.

Features of use:

Use during pregnancy or feeding by a breast.
During pregnancy or during feeding by a breast drug is contraindicated.

Children. To children up to 18 years drug is not appointed.

Treatment termination. In case of a sudden dose decline or after the end of treatment by Levokom ретард behind a condition of patients it is necessary to establish careful control. It is especially important for the patients receiving antipsychotic means.

In need of anesthesia use by Levok ретард so much time how many the patient is able to accept drug can be applied. At the temporary termination of treatment because of anesthesia reception of a standard dose can be resumed as soon as the patient is able to accept drug.

Use for patients of advanced age.
The above-stated recommendations concern also patients of advanced age and are based on clinical data on use of a levodopa / карбидопы in these age groups.

Use at disturbances of functions of a liver and kidneys.
Any dose adjustment is not necessary.
As well as monotherapy by a levodopa, Levok ретард can cause the spontaneous movements and mental disturbances connected with increase in level of dopamine in a brain and can demand a drug dose decline.
All patients need constant observation regarding identification of depressive frustration. Extra care is necessary at treatment of patients with mental disturbances (including in the anamnesis). When strengthening psychotic symptomatology by Levok ретард it is necessary to cancel.

The left lump ретард should be applied with care to patients with a serious cardiovascular or pulmonary illness, bronchial asthma, renal or endocrine disturbances, a peptic ulcer, hematemesis and spasms in the anamnesis.

The left lump ретард should be taken with caution also to patients with a fresh myocardial infarction and existence of atrial, nodal or ventricular arrhythmia. At such patients careful control of cordial function, especially in an initiation of treatment and selection of a dose is necessary.

In need of Levokom's use ретард patients with chronic otkrytouglovy glaucoma constant control of changes of intraocular pressure is necessary.

At the sudden termination of treatment the risk of development of a symptom complex similar to a malignant antipsychotic syndrome which is shown by muscular rigidity, fervescence, mental disorders and increase in level of a kreatinfosfokinaza in blood serum is possible. Therefore at sharp reduction of a dose or drug withdrawal it is necessary to establish careful control of a condition of patients, especially if they receive antipsychotic means.

Levokom's use ретард for treatment of pharmakogenny extrapyramidal reactions, and also a chorea of Gentington is not recommended.
At long therapy periodic definition of functions of a liver, kidneys, the hemopoietic bodies and cardiovascular system is recommended.

Laboratory tests.
The levodopa and karbidopa cause deviations in indicators of many laboratory tests. It can be observed also at Levokom's use ретард and includes, in particular changes of levels: alkaline phosphatase, aspartate aminotransferase, alaninaminotranspherase, lactate dehydrogenase, bilirubin, urea of blood, creatinine, uric acid, and also positive test result of Koombs.
Besides, decrease in level of hemoglobin and a hematocrit, increase in level of glucose in blood, emergence of leukocytes and blood in urine can be observed.

When using test strips for identification of a ketonuria a levodopa / карбидопа can cause emergence of false positive reaction to existence of ketonic bodies. This reaction does not change at boiling of tests of urine.
The false negative take can be shown when using a glyukozooksidazny method of definition of a glucosuria.

Ability to influence the speed of reactions at control of motor transport or work with other mechanisms.
The patients receiving therapy by a levodopa at whom cases of drowsiness and/or sudden sleepy falling were noted have to be warned about need of abstention from driving and robots with the equipment. Besides, it is necessary to consider in that case a possibility of a dose decline or the termination of treatment.

Side effects:

From the side effects revealed at a medical use often meet: anorexia; hallucinations, nonsense, drowsiness, nightmares, mental exhaustion, insomniya; dyskinesia, the chorea, dystonia, extrapyramidal and motive frustration, a phenomenon of "inclusion switching off" (bradykinesia) can arise in several months and even years after an initiation of treatment a levodopa and is probably connected with progressing of a disease (in such cases correction of doses with an interval between them can be required); irregular cordial reductions; orthostatic disturbances, tendency to a loss of consciousness, loss of consciousness; nausea, vomiting, a xerostomia, feeling of bitterness in a mouth.

Loss or increase in body weight can sometimes take place; ataxy, strengthening of a tremor of hands; increase in arterial pressure; locks, diarrhea, sialorrhea, dysphagy, meteorism; hypostases; myospasmus, dark coloring of urine, adynamy; sudden exacerbation of associated diseases.

In single cases at Levokom's use ретард can arise: leukopenia, hemolitic and other forms of anemia, thrombocytopenia; agitation, feeling of horror, disturbance of thinking, disorientation; headache, increase libido, anesthesia, spasms; a malignant antipsychotic syndrome (which is shown by fever and muscular rigidity), paresthesias; gait disturbance; sight illegibility, nictitating spasm; activation of a latent syndrome of Horner; diplopia, mydriasis, okulogirny crisis; phlebitis; dyspepsia, an abdominal pain, dark coloring of saliva, the raised stertost of teeth, a hiccups, gastrointestinal bleedings, a glossodynia, duodenal ulcers; vascular hypostasis, small tortoiseshell, itch, face reddening, alopecia, dieback, hyperhidrosis, dark coloring of sweat, activation of a malignant melanoma, Shenlyayn-Genokh's purple; ischuria, urine incontience, priapism.

Very seldom - an agranulocytosis.

Interaction with other medicines:

Care at simultaneous use of Levokom is necessary ретард with the following medicines:
Anti-hypertensive drugs.

At use of a levodopa / карбидопы with separate anti-hypertensive drugs development of symptomatic orthostatic disturbances therefore in the course of selection of a dose of Levokom ретард dose adjustment of the accompanying anti-hypertensive drugs is necessary is possible.

Antidepressants.
Occasionally at combined use of a levodopa / карбидопы and tricyclic antidepressants there can be side effects in the form of arterial hypertension and dyskinesia.

Anticholinergics.
The left lump ретард can be applied together with the anticholinergics showing synergistic action with a levodopa concerning weakening of a tremor. However their combined use can strengthen spontaneous motive disturbances. Anticholinergics can strengthen effects of a levodopa due to the slowed-down absorption. In such cases dose adjustment of a levodopa / карбидопы is necessary.

Other protivoparkinsonichesky means.
Together with Levokom ретард anticholinergics, antagonists of dopamine, амантадин can be applied. At the same time, if these means are appointed in addition to the therapy which is carried out by Levokom ретард correction of doses of the specified means can be required.

Amantadin shows synergy action with a levodopa and can strengthen side effects of a levodopa. In this regard dose adjustment of a levodopa / карбидопы can be required.
Combined use of a selegelin with a levodopa / карбидопой can provoke heavy orthostatic disturbances.

Other medicines
As the karbidopa prevents easing of the effects of a levodopa caused by use of a pyridoxine (B6 vitamin) by Levok ретард can be applied by the patients receiving in addition a pyridoxine.

Antagonists dopamine D2 receptors (for example, fenotiazina, phenyl propyl ketones, рисперидон), benzodiazepines and antituberculous remedies can weaken therapeutic effect of a levodopa.

Positive influence of a levodopa at Parkinson's disease can be weakened at combined use with Phenytoinum and a papaverine. In such cases careful control from the doctor because of a possibility of decrease in efficiency of treatment is necessary.

Combined use of inhibitors of a katekholometiltransferaza (толкапон, энтакапон) and levodopas / карбидопы can increase bioavailability of a karbidopa.

Metoclopramidum accelerates gastric emptying and can increase Levokom's bioavailability ретард.

Sympathomimetics can exponentiate cardiovascular side effects of a levodopa.

Combined use of ferrous sulfate and levodopa / карбидопы can reduce absorption of a levodopa.

As the levodopa competes with separate amino acids, absorption of a levodopa can be broken at some patients who are on the diet enriched with proteins.

Contraindications:

Drug is contraindicated to patients with zakrytouglovy glaucoma.
It is not necessary to accept drug along with MAO inhibitors. These drugs need to be cancelled in two weeks prior to Levokom's appointment ретард.
Use of drug is contraindicated to patients with the established hypersensitivity to any of its components.
The levodopa can stimulate development of a malignant melanoma therefore patients should not appoint drug with suspicion of not diagnosed skin diseases or with a melanoma in the anamnesis.
Drug is contraindicated during pregnancy and feeding by a breast, to children aged up to 18 years.

Overdose:

Symptoms: precursory symptoms – muscular twitchings, a nictitating spasm; arterial hypertension, increase in heart rate, deterioration in appetite. Confusion of consciousness, alarming excitement, sleeplessness, concern.

Treatment: it is artificial to cause vomiting, to urgently wash out a stomach. Symptomatic therapy: infusions are appointed with care, pay attention to passability of respiratory tracts; at emergence of arrhythmia apply the corresponding treatment under control of an ECG. Value of dialysis for treatment of the phenomena of overdose is not studied. Use of a pyridoxine is inefficient.

Storage conditions:

To store in the place, unavailable to children, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging; on 3 or 10 blister strip packagings in a pack cardboard.