Nakom tablets 250 + 25mg, No. 100

Treatment of Parkinson's disease and Parkinson's syndrome.

Inside.
The dose should be selected individually for each patient, which may require both a correction of the individual dose and the frequency of taking the drug. The shape of the tablet allows it to be divided into two parts with minimal effort.
The initial daily dose is 1/2 (half) tablet 1 or 2 times a day. However, this may not provide the optimal amount of carbidopa required by many patients. If necessary, add 1/2 tablet every day or every other day until the optimal effect is achieved. The effect is observed already within the first day, sometimes already after one dose. The full effect of the drug is achieved within up to seven days.
Studies have shown that the saturation of peripheral decarboxylases of aromatic 1-amino acids is achieved by introducing 70-100 mg of carbidopa per day.
If the patient receives a lower dose of carbidopa, the likelihood of nausea and vomiting is higher.
When prescribing NakomЃ, you can continue to take standard antiparkinsonian drugs (with the exception of levodopa in the form of monotherapy), while dose adjustment is required.
Switching from levodopa drugs. Reception of levodopa should be discontinued at least 12 hours before starting treatment with NakomЃ (24 hours - in the case of using prolonged-acting levodopa drugs). The daily dose of NakomЃ should provide approximately 20% of the previous daily dose of levodopa.
For patients taking more than 1500 mg of levodopa, the initial dose of NakomЃ is 25/250 mg 3 or 4 times a day.
Supportive therapy. If necessary, the dose of NakomЃ can be increased by 1 tablet every day or every other day until the maximum dose is reached - 8 tablets per day. Experience with a daily dose of carbidopa exceeding 200 mg is limited.
The maximum recommended dose is eight tablets of NakomЃ per day (200 mg of carbidopa and 2000 mg of levodopa), which corresponds to approximately 3 mg / kg of carbidopa and 30 mg / kg of levodopa per kilogram of body weight for a patient weighing 70 kg.
Elderly patients: there is extensive experience with the use of levodopa and carbidopa in elderly patients. No dose adjustment is required.
Patients with renal / hepatic impairment: No dose adjustment is required.

One tablet contains:

active substances: levodopa - 250,000 mg,

carbidopa - 25,000 mg;

Excipients:

pregelatinized starch - 45,000 mg, corn starch - 6,500 mg, coloring agent blue indigotin E132 - 0,072 mg, magnesium stearate - 4,200 mg; microcrystalline cellulose up to 380,000 mg.

Х hypersensitivity to the components of the drug;
Х concomitant use of non-selective monoamine oxidase (MAO) inhibitors;
Х an interval of less than two weeks after the end of taking MAO inhibitors;
Х angle-closure glaucoma;
Х melanoma or suspicion of it;
Х skin diseases of unknown etiology;
Х age up to 18 years (the safety of using the drug in young and middle-aged children has not been established);
Х lactation period.

Carefully

Х myocardial infarction with rhythm disturbances (history);
Х chronic heart failure and other serious diseases of the cardiovascular system;
Х severe lung diseases, including bronchial asthma;
Х epileptic and other seizures (history);
Х erosive and ulcerative lesions of the gastrointestinal tract (risk of bleeding from the upper gastrointestinal tract);
Х diabetes mellitus and other decompensated endocrine diseases;
Х severe renal and / or hepatic impairment;
Х open-angle glaucoma;
Х extrapyramidal reactions caused by the use of the drug;
Х pregnancy.

Tradename:

NakomЃ.

International non-proprietary name:

levodopa + carbidopa.

Dosage form:

pills.

Composition:

One tablet contains:

active substances:

levodopa - 250,000 mg

carbidopa - 25,000 mg;

Excipients:

pregelatinized starch - 45,000 mg, corn starch - 6,500 mg, coloring agent blue indigotin E132 - 0,072 mg, magnesium stearate - 4,200 mg; microcrystalline cellulose up to 380,000 mg.

Description : oval biconvex tablets of blue color with white blotches and individual blotches of dark blue color, with a notch on one side.

Pharmacotherapeutic group:

antiparkinsonian agent (dopamine precursor + peripheral decarboxylase inhibitor).

Pharmacological properties

Pharmacodynamics
Antiparkinsonian combined agent - a combination of carbidopa (an inhibitor of aromatic 1-amino acid decarboxylase) and levodopa (a precursor of dopamine). Relieves and relieves symptoms of Parkinson's disease, including hypokinesia, rigidity, tremors, dysphagia, salivation. The antiparkinsonian effect of levodopa is due to its conversion to dopamine directly in the central nervous system, which leads to replenishment of the dopamine deficiency in the central nervous system (CNS). Dopamine formed in peripheral tissues does not participate in the implementation of the antiparkinsonian effect of levodopa (does not penetrate the central nervous system) and is responsible for most of the side effects of levodopa. Carbidopa - an inhibitor of aromatic L-amino acid decarboxylase, reduces the formation of dopamine in peripheral tissues, which indirectly leads to an increase in the amount of levodopa,entering the central nervous system.
NakomЃ provides adequate symptom relief for Parkinson's disease in more patients. The effect of the drug is manifested within the first days from the beginning of the intake, sometimes after taking the first dose. The maximum effect is achieved within 7 days.
Pharmacokinetics of
Carbidopa. After oral administration of a single dose of carbidopa by healthy people and patients with Parkinson's disease, the maximum concentration (Cmax) in the blood plasma is determined 2-4 hours after ingestion by healthy people and after 1.5-5 hours in patients with Parkinson's disease.
Excretion of the drug by the kidneys and intestines is approximately the same in both groups. Excretion of carbidopa unchanged by the kidneys is completely completed after 7 hours. Urinalysis showed the presence of only carbidopa metabolites, no traces of hydrazine were found.
Among the metabolites excreted by the kidneys, the main ones are? -Methyl-3-methoxy-4-hydroxyphenylpropionic acid, as well as? -Methyl-3,4-dihydroxyphenylpropionic acid. They make up about 14 and 10% of the excreted metabolites, respectively. In smaller amounts, 2 other metabolites were found: 3,4-dihydroxyphenylacetone and N-methylcarbidopa. The content of each of these substances is not more than 5% of the total amount of metabolites. In the urine, carbidopa is also found in an unchanged form. Conjugates have not been identified.
Levodopa.When taken orally, levodopa is rapidly absorbed from the gastrointestinal tract (GIT). Absorption is 20-30% of the dose, the maximum concentration in blood plasma (TCmax) when taken orally is 2-3 hours. Absorption depends on the rate of evacuation of gastric contents and on pH. The presence of food in the stomach slows down absorption. Some amino acids from food can compete with levodopa for absorption from the intestine and transport across the blood-brain barrier. It is found in large quantities in the small intestine, liver and kidneys, only about 1-3% penetrates into the brain. It is excreted unchanged by the kidneys (35% within 7 hours) and through the intestines.
The half-life (T1 / 2) of levodopa from blood plasma is about 50 minutes, when administered together with carbidopa - about 2 hours.It is metabolized in all tissues, mainly by decarboxylation with the formation of dopamine, which does not penetrate the blood-brain barrier, metabolites - dopamine, norepinephrine, epinephrine - quickly excreted by the kidneys. Levodopa is also metabolized to dihydroxyphenylacetic acid, homovanillic acid (3-methoxy-4-hydroxyphenylacetic acid) and vanilyl mandelic acid (hydroxy (4-hydroxy-3-methoxyphenyl) acetic acid). Trace amounts of 3-O-methyldopa have been found in blood plasma and cerebrospinal fluid.
Effect of carbidopa on levodopa metabolism.Compared with placebo, in healthy people, carbidopa increases the plasma concentration of levodopa by statistically significant values. Similar results have been demonstrated when taking carbidopa before taking levodopa, and when taking both substances simultaneously.
In one study, pre-administration of carbidopa increased the plasma concentration of a single dose of levodopa by approximately 5-fold, the period when the plasma concentration can still be determined increases from 4 to 8 hours.
When both substances were taken simultaneously, other studies have obtained similar results.
It was shown that patients with Parkinson's disease, who had previously received carbidopa, were injected with single-dose labeled levodopa, the half-life from blood plasma of all metabolites formed from radioactively labeled levodopa increased from 3 hours to 15 hours. The proportion of radioactively labeled levodopa contained in unchanged levodopa, increases at least 3 times when taking carbidopa. After preliminary administration of carbidopa, the concentration of dopamine and homovanillic acid in the blood plasma decreases.

Indications for use

Treatment of Parkinson's disease and Parkinson's syndrome.

Contraindications

Х hypersensitivity to the components of the drug;
Х concomitant use of non-selective monoamine oxidase (MAO) inhibitors;
Х an interval of less than two weeks after the end of taking MAO inhibitors;
Х angle-closure glaucoma;
Х melanoma or suspicion of it;
Х skin diseases of unknown etiology;
Х age up to 18 years (the safety of using the drug in young and middle-aged children has not been established);
Х lactation period.

Carefully

Х myocardial infarction with rhythm disturbances (history);
Х chronic heart failure and other serious diseases of the cardiovascular system;
Х severe lung diseases, including bronchial asthma;
Х epileptic and other seizures (history);
Х erosive and ulcerative lesions of the gastrointestinal tract (risk of bleeding from the upper gastrointestinal tract);
Х diabetes mellitus and other decompensated endocrine diseases;
Х severe renal and / or hepatic impairment;
Х open-angle glaucoma;
Х extrapyramidal reactions caused by the use of the drug;
Х pregnancy.

Application during pregnancy and during breastfeeding

Since the effect of the drug on the course of pregnancy in humans is unknown, and in rabbits, the combination of levodopa with carbidopa can cause disruption of the development of internal organs and skeleton, the use of NakomЃ during pregnancy is possible only if the intended benefit to the mother outweighs the potential risk to the fetus ...
It is not known whether levodopa and carbidopa are excreted in breast milk, therefore, when prescribing NakomЃ during lactation, the question of stopping breastfeeding should be decided.

Method of administration and dosage

Inside.
The dose should be selected individually for each patient, which may require both a correction of the individual dose and the frequency of taking the drug. The shape of the tablet allows it to be divided into two parts with minimal effort.
The initial daily dose is 1/2 (half) tablet 1 or 2 times a day. However, this may not provide the optimal amount of carbidopa required by many patients. If necessary, add 1/2 tablet every day or every other day until the optimal effect is achieved. The effect is observed already within the first day, sometimes already after one dose. The full effect of the drug is achieved within up to seven days.
Studies have shown that the saturation of peripheral decarboxylases of aromatic 1-amino acids is achieved by introducing 70-100 mg of carbidopa per day.
If the patient receives a lower dose of carbidopa, the likelihood of nausea and vomiting is higher.
When prescribing NakomЃ, you can continue to take standard antiparkinsonian drugs (with the exception of levodopa in the form of monotherapy), while dose adjustment is required.
Switching from levodopa drugs. Reception of levodopa should be discontinued at least 12 hours before starting treatment with NakomЃ (24 hours - in the case of using prolonged-acting levodopa drugs). The daily dose of NakomЃ should provide approximately 20% of the previous daily dose of levodopa.
For patients taking more than 1500 mg of levodopa, the initial dose of NakomЃ is 25/250 mg 3 or 4 times a day.
Supportive therapy. If necessary, the dose of NakomЃ can be increased by 1 tablet every day or every other day until the maximum dose is reached - 8 tablets per day. Experience with a daily dose of carbidopa exceeding 200 mg is limited.
The maximum recommended dose is eight tablets of NakomЃ per day (200 mg of carbidopa and 2000 mg of levodopa), which corresponds to approximately 3 mg / kg of carbidopa and 30 mg / kg of levodopa per kilogram of body weight for a patient weighing 70 kg.
Elderly patients: there is extensive experience with the use of levodopa and carbidopa in elderly patients. No dose adjustment is required.
Patients with renal / hepatic impairment: No dose adjustment is required.

Side effect

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: very often (? 1/10), often (? 1/100, <1/10), infrequently (? 1/1000, < 1/100), rarely (? 1/10000, <1/1000) and very rarely (<1/10000); frequency unknown - the frequency of occurrence of the events cannot be determined from the available data.
The most common side effects are dyskinesias, including chorea-like, dystonic and other involuntary movements, and nausea. Muscle twitching and blepharospasm can be considered early signs on the basis of which a decision can be made to reduce the dose.
Benign, malignant and unspecified neoplasms, including cysts and polyps, the
frequency is unknown:malignant melanoma.
From the side of the hematopoietic organs
rarely: leukopenia, anemia (including hemolytic), thrombocytopenia, agranulocytosis.
From the side of the immune system
rarely: angioedema.
From the side of metabolism,
often: anorexia;
frequency unknown: weight loss or gain, edema.
On the part of the psyche,
often: sleep disturbances, including nightmares, hallucinations, depression (including those with suicidal intentions), confusion;
infrequently: agitation;
rarely: psychotic reactions, including delusions, and paranoid thinking, increased libido.
In patients receiving dopamine antagonists, pathological addictions to gambling, hypersexuality, compulsive waste (craving for purchases), gluttony and overeating, and increased libido are observed. The reactions listed above generally disappeared after lowering the dose of the drug or discontinuing treatment.
frequency unknown: anxiety, disorientation, euphoria, insomnia, bruxism.
From the side of the nervous system,
very often: dyskinesias, including chorea, dystonia and other involuntary movements;
often: episodes of bradykinesia ('on-off' -syndrome), dizziness, paresthesia, drowsiness, including less often daytime drowsiness and episodes of sudden falling asleep;
infrequently: syncope;
rarely: dementia, convulsions;
frequency unknown: ataxia, hand tremor, extrapramidal disorders, neuroleptic malignant syndrome, muscle twitching, headache, decreased intellectual acuity, trismus, activation of latent Bernard-Horner syndrome, insomnia, nervousness, euphoria, numbness, fainting, falls, gait disturbances, feeling irritation, compulsions.
It was reported about the development of seizures, however, a causal relationship with taking the drug NakomЃ has not been established.
On the part of the sensory organs, the
frequency is unknown: blepharospasm, diplopia, blurred vision, dilated pupils, oculogyric crises (tonic convulsions of the outer muscles of the eyeball).
From the side of the cardiovascular system,
often:heart palpitations, orthostatic reactions, including episodes of a decrease in blood pressure;
rarely: arrhythmias, phlebitis, increased blood pressure;
frequency unknown: hot flashes, hyperemia.
On the part of the respiratory system,
often: shortness of breath;
frequency unknown: hoarseness, abnormal breathing.
From the gastrointestinal tract
often: vomiting, diarrhea;
rarely: gastrointestinal bleeding, exacerbation of duodenal ulcers, darkening of saliva;
frequency unknown: dryness of the oral mucosa, salivation, dysphagia, abdominal pain, constipation, bloating, dyspepsia, burning sensation of the tongue, bitterness in the mouth, nausea, belching.
From the side of the skin,
infrequently: urticaria;
rarely: itching, hemorrhagic vasculitis (Shenlein-Henoch purpura), alopecia, rash, darkening of sweat;
frequency unknown: increased sweating.
From the urinary system,
rarely: darkening of urine.
frequency unknown: urinary incontinence, urinary retention.
From the musculoskeletal and connective tissue
disorders infrequently: muscle cramps;
frequency unknown: muscle twitching.
On the part of the reproductive system, the
frequency is unknown: priapism.
General disorders and disorders at the injection site
are often: chest pain;
frequency unknown: asthenia, edema, weakness, malaise, fatigue, neuroleptic malignant syndrome.
Laboratory indicators, the
frequency is unknown: an increase in the activity of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, an increase in the content of bilirubin, urea nitrogen in the blood plasma, urea in the blood plasma, hypercreatininemia, hyperuricemia, positive Coombs test.
Decreases in hemoglobin and hematocrit levels, hyperglycemia, leukocytosis, bacteriuria, hematuria have been reported.
Preparations containing carbidopa and levodopa can cause a false-positive reaction to ketone bodies in the urine if test strips are used to determine ketonuria. This reaction will not change after boiling urine samples. False negative results can be obtained using the glucose oxidase method for the determination of glucosuria.

Overdose

In case of an overdose, the severity of the symptoms listed in the 'side effects' section increases.
Treatment: gastric lavage, intake of activated carbon; close observation and electrocardiographic monitoring should be provided for the timely detection of arrhythmias; if necessary, adequate antiarrhythmic therapy should be carried out. Measures for an acute overdose of NakomЃ are basically the same as for an acute overdose of levodopa. It should be noted that pyridoxine is not effective for removing the action of NakomЃ.
It is also necessary to take into account the concomitant therapy that the patient receives along with the drug NakomЃ.

Interaction with other medicinal products

ѕри одновременном применении с гипотензивными средствами необходимо корректировать дозу последних из-за риска развити¤ ортостатической гипотензии.
ѕри одновременном применении леводопы с ингибиторами моноаминооксидазы (ћјќ) (за исключением ингибиторов ћјќ-¬) возможны нарушени¤ кровообращени¤ (прием ингибиторов ћјќ должен быть прекращен, по крайней мере, за 2 недели до начала приема препарата). Ёто св¤зано с накоплением под вли¤нием леводопы дофамина и норэпинефрина, инактиваци¤ которых заторможена ингибиторами ћјќ, и высокой веро¤тностью развити¤ возбуждени¤, повышени¤ артериального давлени¤ (ј?), тахикардии, покраснени¤ лица и головокружени¤.
—оли железа могут снижать биодоступность леводопы и карбидопы; клиническа¤ значимость такого взаимодействи¤ неизвестна.
ѕри одновременном применении леводопы с ?-адреномиметиками, дитилином и лекарственными средствами дл¤ ингал¤ционной анестезии возможно увеличение риска развити¤ нарушений сердечного ритма.
јнтагонисты D2 дофаминовых рецепторов (например, производные бутирофенона, дифенилбутилпиперидина, тиоксантена, фенотиазина, рисперидона), а также изониазид снижают терапевтический эффект леводопы.
»меютс¤ сообщени¤ о блокировании положительного терапевтического воздействи¤ леводопы в результате приема фенитоина и папаверина.
ѕрепараты лити¤ повышают риск развити¤ дискинезии и галлюцинаций.
ћетилдопа усиливает побочные действи¤.
ќдновременное применение тубокурарина повышает риск возникновени¤ артериальной гипотензии.
јбсорбци¤ леводопы может быть нарушена у пациентов, наход¤щихс¤ на диете с повышенным содержанием белка, поскольку леводопа конкурирует с некоторыми аминокислотами.
 арбидопа преп¤тствует действию гидрохлорида пиридоксина (витамин ¬6), который ускор¤ет метаболизм леводопы в дофамин в периферических ткан¤х.

ќсобые указани¤

ЌакомЃ может быть назначен пациентам, которые уже принимают леводопу в монотерапии. ќднако прием леводопы в однокомпонентной форме необходимо прекратить, по крайней мере, за 12 ч до назначени¤ препарата ЌакомЃ.
” пациентов, которые ранее принимали только леводопу, могут возникать дискинезии, поскольку карбидопа обеспечивает более эффективное проникновение леводопы в головной мозг и, следовательно, образуетс¤ больше дофамина. ѕри возникновении дискинезии может потребоватьс¤ снижение дозы.
 ак и леводопа, леводопа/карбидопа может вызвать непроизвольные движени¤ и психические нарушени¤. —читаетс¤, что эти реакции св¤заны с увеличением уровн¤ дофамина в мозге после введени¤ леводопы, и использование леводопы/карбидопы может вызвать рецидив. ћожет потребоватьс¤ снижение дозы.
¬се пациенты должны находитьс¤ под тщательным наблюдением на предмет развити¤ депрессии с сопутствующими суицидальными наклонност¤ми.
ѕри лечении пациентов, у которых ранее отмечались или в насто¤щее врем¤ наблюдаютс¤ признаки психоза, следует соблюдать меры предосторожности.
—ледует про¤вл¤ть осторожность при сопутствующем введении психоактивных препаратов и леводопы/карбидопы). –анним признаком избыточной дозы у некоторых пациентов может служить блефароспазм.
 ак и в случа¤х применени¤ леводопы, при назначении препарата ЌакомЃ пациентам, перенесшим инфаркт миокарда и имеющим в анамнезе предсердную, узловую или желудочковую аритмии, необходимо тщательное предварительное обследование.
“аким пациентам рекомендуетс¤ регул¤рно проводить кардиологические обследовани¤, в особенности, при назначении первой дозы и в период подбора доз.
Ћеводопу/карбидопу следует примен¤ть с осторожностью у пациентов с т¤желыми сердечно-сосудистыми или легочными заболевани¤ми, бронхиальной астмой, заболевани¤ми почек, печени, эндокринными заболевани¤ми или при наличии указаний на ¤звенную болезнь (из-за возможности желудочно-кишечных кровотечений из верхних отделов пищеварительного тракта) или судороги в анамнезе.
ѕациентам с открытоугольной глаукомой на фоне приема препарата ЌакомЃ необходимо регул¤рно контролировать внутриглазное давление.
ѕрием ингибиторов ћјќ следует прекратить, по крайней мере, за две недели до начала лечени¤ препаратом ЌакомЃ.
ѕри внезапной отмене антипаркинсонических препаратов возможно развитие симптомокомплекса, напоминающего злокачественный нейролептический синдром (мышечна¤ ригидность, повышение температуры тела, психические нарушени¤ и повышение концентрации сывороточной креатининфосфокиназы). Ќеобходимо тщательно обследовать пациентов в период резкого снижени¤ дозы препарата ЌакомЃ или его отмены, особенно, если пациент получает антипсихотические лекарственные средства.
ѕрием леводопы сопровождалс¤ сонливостью и эпизодами внезапного засыпани¤.
 райне редко сообщалось о случа¤х внезапного засыпани¤ в течение повседневной де¤тельности, в некоторых случа¤х без осознани¤ или предупреждающих признаков.
ѕри про¤влении таких признаков рекомендуетс¤ рассмотреть возможность снижени¤ дозы.
Ќеобходимо периодически проводить анализ крови, при длительной терапии рекомендуетс¤ проводить периодический контроль функций сердечно-сосудистой системы, печени и почек.
?сли требуетс¤ обща¤ анестези¤, ЌакомЃ можно принимать до тех пор, пока пациенту разрешен прием препарата внутрь. ?сли лечение прервано временно, то обычна¤ доза может быть назначена вновь, как только пациент будет в состо¤нии снова принимать препарат перорально.
»сследовани¤ показали, что у пациентов с болезнью ѕаркинсона повышен риск развити¤ меланомы, поэтому пациентам, принимающим ЌакомЃ, необходимо проходить регул¤рные обследовани¤ у дерматолога.
Ќе ¤сно, св¤зан ли повышенный риск с болезнью ѕаркинсона или другими факторами, такими как препараты, примен¤емые дл¤ лечени¤ болезни ѕаркинсона.
” пациентов, получающих антагонисты дофамина, наблюдаютс¤ патологические пристрасти¤ к азартным играм, гиперсексуальность, компульсивные растраты (т¤га к покупкам), обжорство и переедание, повышенное либидо. ѕри развитии вышеперечисленных симптомов рекомендуетс¤ коррекци¤ дозы/лечени¤.
ЌакомЃ не рекомендуетс¤ примен¤ть дл¤ лечени¤ экстрапирамидных расстройств, вызванных лекарственными препаратами.
ѕища с высоким содержанием белка может нарушать абсорбцию препарата.

¬ли¤ние на способность управл¤ть транспортными средствами, механизмами

¬ очень редких случа¤х леводопа может вызывать сонливость и случаи внезапного наступлени¤ сна. ¬ период лечени¤ препаратом ЌакомЃ следует информировать пациентов о возможности внезапного засыпани¤. ѕациентам с сонливостью и испытавшим внезапное засыпание (случаи внезапного засыпани¤) следует воздержатьс¤ от вождени¤ автотранспорта и зан¤тий потенциально опасными видами де¤тельности, требующими повышенной концентрации внимани¤ и быстроты психомоторных реакций.

‘орма выпуска

“аблетки 250 мг/25 мг
ѕо 10 таблеток в блистер Al/PVC, 10 блистеров в картонную пачку вместе с инструкцией по применению.

”слови¤ хранени¤

¬ сухом защищенном от света месте, при температуре не выше 25 ?—.
’ранить в недоступном дл¤ детей месте.

—рок годности

3 years.
Do not use after the expiration date printed on the package.

Special precautions for disposal of unused product

No special precautions are required when disposing of unused product.

Vacation conditions

On prescription.