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

Composition:One tablet contains: active ingredients: 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 impregnations and separate impregnations of dark blue color, with a notch on. one side.

Pharmacotherapeutic group:An antiparkinsonian agent (dopamine precursor + decarboxylase peripheral inhibitor)

ATX: & nbsp

N.04.B.A.02 Levodopa and a decarboxylase inhibitor

Pharmacodynamics:An antiparkinsonian combination is a combination of carbidopa (aromatic 1-amino acid decarboxylase inhibitor) and levodopa (a precursor of dopamine).Weaken and eliminate the symptoms of Parkinson's disease and including hypokinesia, rigidity, tremor, dysphagia, salivation. The antiparkinsonian action of levodopa is due to its transformation into dopamine directly into the central nervous system, which leads to the replacement of the dopamine deficiency in the central nervous system (CNS). The dopamine formed in the peripheral tissues does not participate in the realization of the antiparkinsonian effect of levodopa (does not penetrate the central nervous system) and is responsible for the majority of side effects of levodopa. Carbidopa is an inhibitor of decarboxylase of aromatic L-amino acids, reduces the formation of dopamine in peripheral tissues, which indirectly leads to an increase in the amount of levodopa entering the CNS. Nacom® provides an adequate reduction in the symptoms of Parkinson's disease in a larger number of patients. The effect of the drug manifests itself during the first 24 hours after the start of the procedure, sometimes after the first dose. The maximum effect is achieved within 7 days.

Pharmacokinetics:

Carbidopa. After ingestion by healthy people and patients with Parkinson's disease of a single dose of carbidopa, 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.The excretion of the drug by the kidneys and intestines is approximately the same in both groups. Isolation of carbidopa in an unchanged form by the kidneys is completely completed after 7 hours. The analysis of urine showed the presence of only metabolites of carbidopa, traces of hydrazine were not found. Among the metabolites released by the kidneys, the main ones are α-methyl-3-methoxy-4-hydroxyphenylpropionic acid, as well as α-methyl-3,4-dihydroxyphenylpropionic acid. They make up about 14 and 10% of excreted metabolites, respectively. In smaller amounts, 2 other metabolites were detected: 3,4-dihydroxyphenylacetone and N-methylcarbidopa. The content of each of these substances is not more than 5% of the total amount of metabolites. Urine is also found carbidopa in an unchanged form. Conjugates have not been identified.

Levodopa. Levodopa when ingested quickly absorbed from the gastrointestinal tract (GIT). Absorption is 20-30% of the dose, the maximum concentration in the blood plasma (TCmax) with oral intake - 2-3 hours. Absorption depends on the rate of evacuation of stomach contents and pH. The presence of food in the stomach slows down absorption. Some food amino acids can compete with levodopa for absorption from the intestine and transport through the blood-brain barrier.In large quantities is contained in the small intestine, liver and kidneys, only about

1-3% penetrate the brain. In unchanged form is excreted by the kidneys (35% within 7 hours) and through the intestine.

The half-life of levodopa from 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 Also metabolized to dihydroxyphenylacetic acid, homovanilic acid (3-methoxy-4-hydroxyphenylacetic acid) and vanillylmandelic acid (hydroxy (4-hydroxy-3-methoxyphenyl) acetic acid). Trace amounts of 3-O-methyldopa have been detected in blood plasma and in cerebrospinal fluid.

Effect of carbidopa on the metabolism of levodopa. In comparison with placebo, in healthy people carbidopa increases the concentration of levodopa in the blood plasma by statistically significant values. Similar results were demonstrated, both with carbidopa intake before taking levodopa, and with simultaneous administration of both substances.In one study, the preliminary administration of carbidopa increases the plasma concentration of a single dose of levodopa by approximately 5-fold, the period when the concentration in the blood plasma can still be determined increases from 4 to 8 hours. At the same time, both substances were obtained in other studies, similar results were obtained.

It was shown that patients with Parkinson's disease who had previously received carbidopa were given a single-labeled levodopa, the half-life of all metabolites formed from radiolabeled levodopa from the blood plasma increased from 3 hours to 15 hours. The proportion of radiolabeled levodopa contained in unchanged levodopa, increases at least 3 times when taking carbidopa. After preliminary administration of carbidopa, the concentrations of dopamine and homovanilic acid in the blood plasma are reduced.

Indications:Treatment of Parkinson's Disease and Parkinson's Syndrome.

Contraindications:

- hypersensitivity to the components of the drug;

- simultaneous reception nonselective monoamine oxidase inhibitors (MAO);

- interval less than two weeks after the end of the intake of MAO inhibitors;

- angle-closure glaucoma;

- melanoma or suspicion of it;

- skin diseases of unknown etiology;

- age under 18 years (safety of application of a preparation at children of younger and middle age is not established);

- lactation period.

Carefully:

- myocardial infarction with rhythm disturbances (in the anamnesis);

- chronic heart failure and other severe diseases of the cardiovascular system;

- severe lung diseases, including bronchial asthma;

- epileptic and other convulsive seizures (in the anamnesis);

- erosive and ulcerative lesions of the gastrointestinal tract (risk of bleeding from the upper sections of the gastrointestinal tract);

- diabetes mellitus and other decompensated endocrine diseases;

- severe renal and / or hepatic insufficiency;

- open-angle glaucoma;

- extrapyramidal reactions caused by the use of the drug;

- pregnancy.

Pregnancy and lactation:

Since the effect of the drug on the course of pregnancy in humans is unknown, and in rabbits a combination of levodopa with carbidopa can cause disruption of the development of internal organs and skeleton, the use of Nacom® during pregnancy is possible only in the event that,if the intended use for the mother exceeds the potential risk to the fetus.

It is not known whether they are excreted in human milk levodopa and carbidopa, therefore, when Nakom® is prescribed for the lactation period, the question of stopping breastfeeding should be resolved.

Dosing and Administration:

Inside.

The dose should be selected individually for each patient, which may require both adjusting the individual dose and the frequency of taking the drug. The shape of the tablet allows you to divide it into two parts with minimal effort.

The initial daily dose is 1/2 (half) of the tablet 1 or 2 times a day. However, the optimum amount of carbidopa needed by many patients may not be ensured. If necessary, add 1/2 tablet every day or every other day until the optimal effect is achieved. The effect is observed already during the first day, sometimes after only one dose. The full effect of the drug is achieved in terms of up to seven days.

Studies have shown that saturation of peripheral decarboxylases of aromatic 1-amino acids is achieved by administering 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 Nakom® is prescribed, it is possible to continue taking standard antiparkinsonian drugs (except for levodopa in the form of monotherapy), and dosage correction is required.

Transition from levodopa preparations. Levodopa should be discontinued at least 12 hours prior to initiation of Nakom® treatment (24 hours after levodopa with prolonged action). The daily dose of Nacom® should provide approximately 20% of the previous daily dose of levodopa. For patients taking more than 1500 mg of levodopa, the initial dose of Nacom® is 25/250 mg 3 or 4 times a day.

Supportive therapy. If necessary, the dose of Nacom® can be increased by 1 tablet every day or every other day until the maximum dose is reached - 8 tablets per day. The experience of taking a daily dose of carbidopa exceeding 200 mg is limited.

The maximum recommended dose is eight tablets of Nacom® 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 with a body weight of 70 kg.

Older patients: There is extensive experience in the use of levodopa and carbidopa in elderly patients. Correction of the dose is not required.

Patients with renal / hepatic insufficiency: correction of the dose is not required.

Side effects:

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 is unknown - the frequency of occurrence of phenomena can not be determined on the basis of available data.

The most common side effects are dyskinesias, including chorea-like, dystonic and other involuntary movements, as well as nausea. Early signs, on the basis of which a decision can be made to reduce the dose, can be considered muscle twitching and blepharospasm.

Benign, malignant and unspecified neoplasms, including cysts and polyps

frequency is unknown: malignant melanoma.

On the part of the organs of hematopoiesis

rarely: leukopenia, anemia (including hemolytic), thrombocytopenia, agranulocytosis.

From the immune system

rarely: angioedema.

From the side of metabolism

often: anorexia;

frequency is unknown: loss or weight gain, swelling.

From the side of the psyche

often: sleep disturbance, including nightmares, hallucinations, depression (including with suicidal intentions), confusion;

infrequently: agitation;

rarely: psychotic reactions, including delirium, and paranoid thinking, increased libido.

In patients receiving dopamine antagonists, there are pathological addictions to gambling, hypersexuality, compulsive waste (craving for purchases), gluttony and overeating, increased libido. The above reactions basically disappeared after a reduction in the dose of the drug or discontinuation of treatment.

frequency is unknown: anxiety, disorientation, euphoria, insomnia, bruxism.

From the nervous system

Often: dyskinesia, including chorea, dystonia and other involuntary movements;

often: episodes of bradykinesia ("on-off" -syndrome), dizziness, paresthesia, drowsiness, including less drowsiness during the day and episodes of sudden falling asleep;

infrequently: syncope;

rarely: dementia, convulsions;

frequency is unknown: ataxia, hand tremors, extraparamid disorders, malignant neuroleptic syndrome, muscle twitching, headache, decreased intelligence, trismus, activation of Bernard-Horner's latent syndrome, insomnia, nervousness, euphoria, numbness, fainting, falls, gait disturbance, irritation, compulsions . There have been reports of seizures, but the cause-and-effect relationship with taking Nakom® is not established.

From the sense organs

frequency is unknown: Blepharospasm, diplopia, visual impairment, dilated pupils, oculogic crises (tonic cramps of the external muscles of the eyeball).

From the side of the cardiovascular system

often: heart palpitations, orthostatic reactions, including episodes of blood pressure lowering;

rarely: arrhythmias, phlebitis, increased blood pressure;

frequency is unknown: hot flashes, hyperemia.

From the respiratory system

often: dyspnea;

frequency is unknown: hoarseness of voice, abnormal character of breathing.

From the gastrointestinal tract

often: vomiting, diarrhea;

rarely: gastrointestinal bleeding, exacerbation of duodenal ulcer, darkening of saliva;

frequency is 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 skin

infrequently: hives;

rarely: itching, hemorrhagic vasculitis (purple Shenlaine-Genocha), alopecia, rash, darkening sweat;

frequency is unknown: increased sweating.

From the side of the urinary system

rarely: darkening of urine.

frequency is unknown: urinary incontinence, urinary retention.

From the musculoskeletal and connective tissue

infrequently: muscle cramps;

frequency is unknown: muscle twitching.

From the side of the reproductive system

frequency is unknown: priapism.

General disorders and disorders at the site of administration

often: pain in the chest;

frequency is unknown: asthenia, swelling, weakness, malaise, fatigue, malignant neuroleptic syndrome.

Laboratory indicators

frequency is unknown: increased activity of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, increased bilirubin, urea nitrogen in blood plasma, urea in blood plasma, hypercreatininaemia, hyperuricemia, positive Coombs test.

There was reported a decrease in hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria, hematuria.

Drugs 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 by using a glucose oxidase method for determining glucosuria.

Overdose:

When an overdose increases the severity of the symptoms listed in the "side effect" section.

Treatment: gastric lavage, reception of activated charcoal; careful monitoring and electrocardiographic monitoring should be provided in order to detect arrhythmias in a timely manner; if necessary, adequate antiarrhythmic therapy should be provided. Measures for acute overdose of Nacom® are basically the same as in acute overdose of levodopa. It should be noted that pyridoxine It is not effective for removing the effect of Nacom®.

It is also necessary to take into account the concomitant therapy that the patient receives along with the Nacom® drug.

Interaction:

When used simultaneously with antihypertensive drugs It is necessary to adjust the dose of the latter because of the risk of developing orthostatic hypotension.

With simultaneous application of levodopa with monoamine oxidase inhibitors (MAO) (with the exception of MAO-B inhibitors), circulatory disorders are possible (administration of MAO inhibitors should be discontinued, by extreme least 2 weeks before the start of the drug). This is due to the accumulation under the influence of levodopa dopamine and norepinephrine, the inactivation of which is inhibited by MAO inhibitors, and a high probability of development of excitation, increased blood pressure (BP), tachycardia, facial flushing and dizziness.

Ferric salts can reduce the bioavailability of levodopa and carbidopa; the clinical significance of this interaction is unknown.

With simultaneous application of levodopa with β-adrenomimetics, dithiline and drugs for inhalation anesthesia possibly an increased risk of heart rhythm disturbances.

D2 antagonists of dopamine receptors (for example, butyrophenone derivatives, diphenylbutylpiperidine, thioxanthene, phenothiazine, risperidone), and isoniazid reduce the therapeutic effect of levodopa.

There are reports of a blocking of the positive therapeutic effect of levodopa as a result of taking phenytoin and papaverine. Lithium preparations increase the risk of dyskinesia and hallucinations. Methyldopa strengthens side effects.

Simultaneous application tubocurarine increases the risk of arterial hypotension.

Absorption of levodopa may be impaired in patients on a diet with high protein content, since levodopa competes with some amino acids.

Carbidopa interferes with the action pyridoxine hydrochloride (vitamin B6), which accelerates the metabolism of levodopa to dopamine in peripheral tissues.

Special instructions:

Nakom® can be prescribed to patients who are already taking levodopa in monotherapy. However, the use of levodopa in a single-component form should be discontinued, at least 12 hours before the administration of Nacom®.

In patients who have previously taken only levodopa, dyskinesia may occur, as carbidopa provides a more effective penetration of levodopa into the brain and, consequently, more dopamine is formed.When dyskinesia occurs, a dose reduction may be required.

As well as levodopa, levodopa / carbidopa can cause involuntary movements and mental disorders. It is believed that these reactions are associated with an increase in the level of dopamine in the brain after the administration of levodopa, and the use of levodopa / carbidopa can cause a relapse. A dose reduction may be required.

All patients should be carefully monitored for the development of depression with concomitant suicidal tendencies. In the treatment of patients who have previously experienced or are currently experiencing psychosis, precautions should be followed. Caution should be exercised with the concomitant administration of psychoactive drugs and levodopa / carbidopa). An early indication of an excessive dose in some patients may be blepharospasm. As with levodopa, when Nakom® is prescribed to patients who have had a myocardial infarction and have a history of atrial, nodular or ventricular arrhythmias, a thorough preliminary examination is necessary. Such patients are recommended to carry out cardiac examinations on a regular basis, especially when administering the first dose and during the dose selection period.

Levodopa / carbidopa should be used with caution in patients with severe cardiovascular or pulmonary diseases, bronchial asthma, kidney, liver, endocrine diseases or with evidence of peptic ulcer disease (due to the possibility of gastrointestinal bleeding from the upper digestive tract) or convulsions in the anamnesis.

Patients with open-angle glaucoma against the background of taking Nakom® should regularly monitor the intraocular pressure. The intake of MAO inhibitors should be discontinued at least two weeks before treatment with Nacom®.

With the sudden withdrawal of antiparkinsonian drugs, the development of a symptom complex resembling a malignant neuroleptic syndrome (muscle rigidity, fever, mental disorders and an increase in serum creatinine phosphokinase concentration) is possible. It is necessary to carefully examine patients during a period of a sharp reduction in the dose of Nacom® or its withdrawal, especially if the patient receives antipsychotic medications. The intake of levodopa was accompanied by drowsiness and episodes of sudden falling asleep.Very rarely reported cases of sudden falling asleep during daily activities, in some cases without awareness or warning signs. When these signs are manifested, it is recommended to consider the possibility of dose reduction. It is necessary to periodically carry out a blood test, with prolonged therapy it is recommended to carry out periodic monitoring of the functions of the cardiovascular system, liver and kidneys.

If general anesthesia is required, Nakom® can be taken as long as the patient is allowed to take the drug inside. If treatment is interrupted temporarily, the usual dose may be administered again as soon as the patient is able to take the drug orally again. Studies have shown that patients with Parkinson's disease have an increased risk of developing melanoma, so patients taking NAC® should undergo regular examinations with a dermatologist.

It is not clear whether an increased risk is associated with Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease.

In patients receiving dopamine antagonists, there are pathological addictions to gambling, hypersexuality, compulsive waste (craving for purchases), gluttony and overeating, increased libido.With the development of the above symptoms, a dose / treatment correction is recommended.

Nakom® is not recommended for the treatment of extrapyramidal disorders caused by medications.

Foods high in protein may interfere with drug absorption.

Effect on the ability to drive transp. cf. and fur:In very rare cases levodopa can cause drowsiness and cases of sudden onset of sleep. During the period of treatment with Nacom®, patients should be informed of the possibility of sudden falling asleep. Patients with drowsiness and experienced sudden falling asleep (cases of sudden falling asleep) should refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 250 mg / 25 mg

Packaging:For 10 tablets per blister A1 / PVC, 10 blisters in a cardboard bundle along with instructions for use.

Storage conditions:In dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:In dry, dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Terms of leave from pharmacies:On prescription

Registration number:П N015500 / 01

Date of registration:19.12.2008

The owner of the registration certificate: Lek dd Lek dd Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Information update date: & nbsp23.08.2015

Illustrated instructions

Instructions

Nacom ® (Nakom® )