Expiration date: 03/2025

The composition and form of issue:

Tablets. 1 tablet contains:

active substances: 

levodopa 250 mg

carbidopa 25 mg

excipients: microcrystalline cellulose starch corn starch pregelatinization blue dye (indigotin E132) magnesium stearate 

in blister 10 tab. in a box 10 blisters.

Description pharmaceutical form:

The tablets are biconvex oval shaped blue color with white patches and some splashes of dark blue color with a notch on one side.

Pharmacokinetics:

Levodopa. Levodopa is rapidly absorbed from the gastrointestinal tract and extensively metabolized. Despite the fact that produce more than 30 different metabolites, mainly levodopa is converted into dopamine, epinephrine, norepinephrine.

After oral administration to patients with Parkinson's disease a single dose of levodopa Tmax is 1, 5-2 hours and maintained at therapeutic level for 4-6 h. the fast Metabolites are excreted in the urine: within 2 h displayed about 1/3 of the dose.

T1/2 of levodopa in plasma is approximately 50 min During simultaneous administration of carbidopa and levodopa T1/2 of levodopa is increased to about 1, 5 hours.

Carbidopa. After oral administration of a single dose of carbidopa Tmax is from 1, 5 to 5 h in patients with Parkinson's disease.

Metabolized in the liver.

Urinary excretion of unchanged drug is mainly completed within 7 h and is 35%.

Among the metabolites excreted with urine, the main ones are alpha-methyl-3-methoxy-4-hydroxyphenylpropionic acid, and alpha-methyl-3, 4-dihydroxyphenylpropionic acid. They are about 14 and 10% of the excreted metabolites, respectively. In smaller numbers found two other metabolite. One of them identified as 3, 4-dihydroxyphenyl-acetone, another — previously as N-methyl-carbidopa. The content of each of these substances is not more than 5% of the total number of metabolites. In the urine detected by the unmodified carbidopa. Conjugates have not been identified.

The effect of carbidopa on the metabolism of levodopa. Carbidopa increases the concentration of levodopa in the blood plasma. When the previous reception of carbidopa levodopa concentration in plasma is increased approximately 5 fold while maintaining therapeutic concentrations in the plasma increases from 4 to 8 h. the simultaneous administration of carbidopa and levodopa were obtained similar results.

When a single dose of levodopa to patients with Parkinson's disease who had previously received carbidopa, T1/2 of levodopa is increased from 3 to 15 h. Concentration of levodopa increased by carbidopa at least 3 times. The concentration of dopamine and homovanillic acid in blood plasma and in the urine decreased with prior ingestion of carbidopa.

Description pharmacological action:

Levodopa reduces the symptoms of Parkinson's disease due to the increase in the content of dopamine in the brain. Carbidopa, which does not penetrate the BBB, inhibits the extracerebral decarboxylation of levodopa, thereby increasing the amount that enters the brain and is converted there into dopamine.

NAC has a more pronounced therapeutic effect compared with levodopa, provides long-term maintenance of therapeutic concentrations of levodopa in the plasma at doses that are approximately 80% lower than those required in the case of a single levodopa.

The drug is during the first day since the start of the reception, sometimes — after the first dose. The maximum effect is achieved within 7 days.

Indications:

The treatment of Parkinson's disease and Parkinsonian syndrome.

Contraindications:

• hypersensitivity to any component of the drug
  
• concomitant use with nonselective MAO inhibitors (these drugs must be completed at least two weeks before the start of drug treatment NAC)
  
• angle-closure glaucoma
  
• melanoma or suspected it
  
• skin diseases of unknown etiology.
  

With caution (requires more careful selection of doses and the safety control treatment):

• myocardial infarction with rhythm disorders (history)
  
• heart failure and other severe diseases of the cardiovascular system
  
• severe lung disease, including asthma
  
• epileptic and other seizures (history)
  
• erosive-ulcerative lesions of the gastrointestinal tract (because of the possibility of bleeding from the upper gastrointestinal tract)
  
• diabetes and other decompensated endocrine diseases
  
• severe renal and/or hepatic insufficiency
  
• open-angle glaucoma.
  

The use in children. The safety of the drug for children younger and middle age is not established and its use for the treatment of children under 18 years not recommended.

Application of pregnancy and breast-feeding:

Pregnancy. The effect of NAC on pregnancy in women is unknown, but it should be noted that the combination of levodopa and carbidopa cause visceral and skeletal changes in animals. Therefore, the use of the drug is possible only in case when expected benefit of treatment to the mother outweighs the potential risk to the fetus.

Lactation. Unknown, stand out with breast milk levodopa and carbidopa. There is one report of excretion of levodopa in breast milk from a nursing mother with Parkinson's disease. Therefore, because of possible serious adverse effects of the drug on the newborn, should take a decision on either the cessation of feeding, or to discontinue the use of the drug NAC, taking into account the importance of the drug to the mother.

Side effects:

The most common side effects are dyskinesias, including korepodobnaya, dystonic and other involuntary movements and nausea. Early signs on the basis of which can be decided on dose reduction may be considered muscle twitching and blepharospasm.

Other side effects

Body as a whole: syncope, chest pain, anorexia.

CVS: arrhythmias and/or palpitations, orthostatic effects including episodes of increase or decrease in blood pressure, phlebitis.

Digestive system: vomiting, gastrointestinal bleeding, exacerbation of duodenal ulcer, diarrhoea, dark saliva.

Hematopoietic system: leukopenia, anemia (including hemolytic), thrombocytopenia, agranulocytosis.

Allergic reactions: angioneurotic edema, urticaria, itching skin disease Shenleyn-Schonlein purpura.

Nervous system/Psychiatry: neuroleptic malignant syndrome (see "Special indications"), episodes of bradykinesia ("on-off"syndrome), dizziness, drowsiness, paresthesia, episodes of psychotic conditions including delusions, hallucinations and paranoid thinking, depression, development of suicidal intent and those without, dementia, sleep disorder, agitation, confusion, increased libido.

In rare cases it was reported the development of seizures, however, a causal relationship with intake of NAC is not installed.

Respiratory system: dyspnoea.

Skin: alopecia, rash, darkening of the secret of the sweat glands.

Urinary system: darkening of urine.

Listed below are other side effects that occurred as a result of taking levodopa, and therefore, they can be observed in the case of the drug NAC:

Gastrointestinal: dyspepsia, dry mouth, feeling of bitterness in the mouth, valoria, dysphagia, bruxism, seizures, hiccups, pain and discomfort in the abdomen, constipation, flatulence, burning sensation of the tongue.

Metabolism: a decrease or increase in body weight, swelling.

CNS: weakness, fainting, fatigue, headache, asthenia, decreased mental activity, disorientation, ataxia, numbness, increased hand tremor, muscle cramps, lockjaw, activation of latent syndrome of Horner, insomnia, anxiety, euphoria, agitation, unsteady gait.

Special senses: diplopia, blurred vision, dilated pupils, ekologichnye crises.

Urogenital system: urinary retention, urinary incontinence, priapism.

Other side effects: hoarseness, malaise, hot flashes of blood to face, neck and chest, dyspnoea, malignant melanoma (see "Contraindications").

Changes in laboratory parameters: increased activity of alkaline phosphatase, AST, ALT, lactate dehydrogenase, increased bilirubin, urea nitrogen in plasma, hypercreatininemia, hyperuricemia, positive Coombs test.

It was reported the decrease in hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria, erythrocyturia.

Drugs containing levodopa + carbidopa may cause false-positive reaction for ketone bodies in the urine, if to determine ketonuria used test strips. This reaction will not change after boiling of the urine samples. False negative results can be obtained by using glucoseoxidase method for the determination of glycosuria.

Drug interactions:

You should take precautions if together with the drug NAC are appointed by the listed below drugs.:

Anti-hypertensive drugs. In patients receiving some antihypertensive drugs, addition of NAC caused symptomatic orthostatic hypotension. Therefore, at the beginning of treatment Nakomom you may need a dose adjustment of antihypertensives.

Antidepressants. With simultaneous application of levodopa with MAO inhibitors (except MAO inhibitors) possibly poor circulation (MAO inhibitors should be discontinued for 2 weeks). This is due to the accumulation under the influence of levodopa, dopamine and norepinephrine, the inactivation of which is inhibited by the MAO inhibitors. As a result, there is a high possibility of excitement, increase in blood pressure, tachycardia, redness of face and dizziness.

There were isolated reports of adverse reactions, including increased blood pressure and dyskinesia, in the case of combined use of tricyclic antidepressants with Nakomom (for patients receiving MAO inhibitors, see section "Contraindications").

The preparations of iron. The bioavailability of carbidopa and/or levodopa is reduced while the use of patient iron sulfate or iron gluconate.

Other drugs. With simultaneous application of levodopa with beta-agonists, ditilinom and means for inhalation anesthesia may increase the risk of cardiac arrhythmias.

Antagonists of D2-receptors of dopamine (e.g. phenothiazines, butyrophenones and risperidone) and isoniazid may reduce the therapeutic effect of levodopa.

There are reports on blocking of the positive therapeutic effects of levodopa in Parkinson's disease resulting from the ingestion of phenytoin and papaverine. For patients taking these medications concurrently with the drug NAC, requires careful observation for early detection of therapeutic action.

Lithium drugs increase the risk of dyskinesia and hallucinations methyldopa intensifies the side effects, concurrent use of tubocurarine increases the risk of arterial hypotension.

The absorption of levodopa may be impaired in some patients on high protein diet because levodopa competes with certain amino acids.

Carbidopa inhibits the action of pyridoxine (vitamin B6), which speeds up the metabolism of levodopa into dopamine in peripheral tissues.

Method of application and dose:

The optimal daily dose must be determined by careful selection for each patient. The tablet form allows you to divide it into two parts with minimal effort.

General provisions. Dosage should be individualized for each patient, which may require as adjustments of individual dose and frequency of medication. Studies show that peripheral DOPA-decarboxylase is saturated by carbidopa at taking the last dose, approximately 70-100 mg per day. Patients receiving a smaller amount of carbidopa may experience nausea and vomiting.

In the case of appointment Nacoma receiving the standard drugs for the treatment of Parkinson's disease, with the exception of those that contain one levodopa, can be continued, and their doses should be adjusted again.

The usual initial dose. Dosage doctor in accordance with the illness and the patient's response to treatment. The initial dose of NAC 250/25 is at the 1/2 table. 1 or 2 times a day. However, this dosage may not produce the optimal amount of carbidopa, which is required to the patient. Therefore, if necessary, added 1/2 table. Nacoma 250/25 every day or every other day to achieve an optimal effect.

The effect is observed on the first day, and sometimes after the first dose. The full effect of the drug is achieved in terms of up to seven days.

Switching from levodopa. The drug levodopa must be discontinued at least 12 h prior to treatment with the drug NAC (for 24 h in the case of the use of levodopa preparations of the prolonged action). Daily dose of NAC should provide about 20% of the previous daily dose of levodopa.

For patients taking more than 1500 mg of levodopa, the initial dose of NAC is 250/25 mg 3 or 4 times a day.

Supportive therapy. If necessary, the dose of NAC can be increased by 1/2 tab. or 1 table. every day or every other day until the maximum dose — 8 tab. a day. Experience receiving daily doses of carbidopa greater than 200 mg is limited.

The maximum recommended dose. The maximum recommended dose is eight tablets per day of NAC (2 g levodopa and 200 mg of carbidopa). About 3 mg of carbidopa and 30 mg of levodopa per kilogram of body weight when the body weight of patient 70 kg.

Overdose:

Overdose NAC enhanced the severity of side effects (see "Side effects").

Treatment: there should be carefully monitored and ECG monitoring the patient to detect possible arrhythmias, if necessary, should be adequate antiarrhythmic therapy. It is necessary to consider the possibility that along with the drug NAC the patient has taken other medicines.

Special instructions:

As in the case of levodopa, the appointment Nacoma patients who have had a heart attack and have atrial, nodal or ventricular arrhythmias, a careful preliminary examination. These patients need to monitor heart activity, with special care in the appointment of the first dose and during the selection of the doses.

Patients with open-angle glaucoma NAC should be administered with caution and under the condition that the intraocular pressure is constantly monitored during treatment.

Because both therapeutic and adverse effects occur more frequently with the combination of carbidopa and levodopa than levodopa one, in the period of dose adjustment, the patients should be carefully monitored. In particular, NAC frequently than levodopa, cause involuntary movements. The emergence of involuntary movements may require lower doses. An early sign of excessive doses in some patients can serve as blepharospasm.

If the therapeutic response to the drug levodopa irregular, and signs and symptoms of Parkinson's are not controlled throughout the day, then go to NAC usually allows to reduce fluctuations in the reaction to drugs.

By reducing certain adverse effects caused by the drug levodopa, the drug NAC provides patients with adequate reduction in the symptoms of Parkinson's disease.

NAC is also indicated for patients with Parkinson's disease taking vitamin preparations that contain pyridoxine hydrochloride (vitamin B6).

NAC is not recommended to eliminate extrapyramidal disorders caused by medications.

The drug NAC can be administered to patients already receiving drugs containing only l-DOPA, however, the intake of levodopa must be discontinued at least 12 h prior to treatment with the drug NAC. NAC should be administered in doses that provide approximately 20% of the previous dose of levodopa (see section "Method of application and dosage").

Patients previously taking levodopa, you may experience dyskinesia, because carbidopa allows more levodopa to reach the brain, and thus produce greater amounts of dopamine. The occurrence of dyskinesias may require a reduction in dose.

As l-DOPA, NAC can cause involuntary movements and mental disorders. It is assumed that these reactions are due to the increase in the content of dopamine in the brain. These effects may require dose reduction. All patients who are taking NAC should be monitored in connection with the possibility of depressive States with suicidal tendencies. Patients who have experienced psychosis, require a cautious approach in selecting therapy.

Should be exercised with concomitant administration of psychotropic drugs and of the drug NAC (see section "Interactions").

With the sudden cancellation of antiparkinson drugs has been described the symptom complex resembling the neuroleptic malignant syndrome including muscular rigidity, increased body temperature, mental disorders, and the increase in the concentration of serum kreatininfosfokinaza.

Therefore, careful examination of patients in a period of sharp decline in dose Nacoma its cancellation, especially if the patient is receiving neuroleptics. As with levodopa, during long-term treatment Nakomom recommended periodic monitoring of liver function, hematopoietic system, cardiovascular system and kidneys.

If you need General anesthesia, the drug NAC can be taken up until the patient permitted oral administration of fluids and drugs.

If treatment is temporarily interrupted, the reception NAC can be resumed at the normal dosage, once a patient will be able to take it orally.