Nacom

Nakom is a drug with dopaminergic and antiparkinsonian action.

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Indications Nakoma

Indicated for shaking palsy, as well as Parkinson's syndrome.

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Release form

Available in tablets, 10 pieces inside 1 blister. One package contains 10 blister strips.

Pharmacodynamics

Levodopa helps reduce the symptoms of shaking palsy by increasing the levels of dopamine inside the brain. Carbidopa, which does not pass through the blood-brain barrier, prevents the process of extracerebral decarboxylation of the substance levodopa, thereby increasing the amount of this element that penetrates into the brain and is converted there into the component dopamine.

The drug has a powerful medicinal effect that exceeds the effectiveness of levodopa. It helps to maintain the medicinal plasma concentration of this element for a long time at dosages that are much lower than those used in cases of using levodopa alone (approximately 80%).

The effect of the drug on the body begins on the first day after the start of the course (in some cases - after taking the first dose). The drug reaches its peak effectiveness after 1 week.

Pharmacokinetics

The absorption of levodopa from the gastrointestinal tract occurs quite quickly, after which active metabolism of this substance occurs. Although this process results in the formation of 30+ different decay products, levodopa is often converted into epinephrine with dopamine and norepinephrine.

When taking the drug internally in a single dose in patients with shaking palsy, the peak indicator occurs after 1.5-2 hours, and the medicinally effective level of the substance is maintained for about 4-6 hours. The decay products are quickly excreted with urine: about a third of the entire dose is excreted in 2 hours.

The plasma half-life of levodopa is approximately 50 minutes. When carbidopa is combined with levodopa, the half-life of levodopa is extended to approximately 1.5 hours.

When a single oral dose of carbidopa is administered, the peak time is 1.5-5 hours in people with shaking palsy. The substance is metabolized in the liver.

The unchanged substance is excreted in urine. This process usually ends after 7 hours and is 35%.

The main breakdown products excreted in urine are α-methyl-tri-methoxy-4-hydroxyphenyl propionic acid and α-methyl-3,4-dihydroxyphenyl propionic acid. These substances make up approximately 14% and 10% (respectively) of the excreted breakdown products. Two more breakdown products are represented in lower concentrations, one of which is the substance 3,4-dihydroxyphenyl acetone, and the second (according to preliminary data) is the element N-methyl carbidopa. The indicators of each of these components make up a maximum of 5% of the total level of breakdown products. Unchanged carbidopa is also determined in urine, but conjugates are not detected.

The effect of carbidopa on the metabolism of the substance levodopa: plasma levels of the latter are increased by carbidopa. In the case of preliminary use of carbidopa, the plasma level of levodopa increases 5 times (approximately), and the period of maintaining medicinal values in the plasma is extended from 4 to 8 hours. In the case of a combination of these two substances, the treatment results are approximately the same.

In the case of a single use of levodopa in people with shaking palsy who previously used carbidopa, the half-life of levodopa increases from 3 to 15 hours. Due to the intake of carbidopa, the level of levodopa also increases (approximately 3 times). It should also be noted that prior medicinal use of carbidopa reduces the content of GVA and dopamine in urine and plasma.

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Dosing and administration

The medicine is taken orally, and the required daily dose is determined after careful individual selection for each patient. Due to the tablet shape, it can be easily divided in half.

General requirements – since the dose is selected individually for each patient, it can be individually adjusted not only in terms of the amount but also the frequency of use. Tests have shown that peripheral dopa decarboxylase receives the required saturation with carbidopa when the latter is used in the amount of about 70-100 mg per day. People who take carbidopa in smaller doses may develop vomiting with nausea.

When prescribing Nakom, the use of standard drugs used to eliminate Parkinsonism (except for those drugs that contain only levodopa) is allowed to continue, but it is necessary to re-select their dosages.

The standard dosage at the initial stages is selected by the attending physician, taking into account the disease being treated, as well as the patient's response to the drug. Usually the initial dosage consists of 0.5 tablets taken 1-2 times a day. But this amount of the drug may be insufficient to provide the amount of carbidopa required by the patient, as a result of which, if necessary, to achieve the desired effect, another 0.5 tablet of the drug may be added (daily or every other day).

The effect of the drug is manifested on the first day, in some cases even immediately after taking the first dose. The full effectiveness of the drug is achieved within the first week.

Switching from levodopa-containing drugs: levodopa should be stopped at least 12 hours before starting Nacom (or 24 hours if extended-release levodopa is used). The daily dose of Nacom should provide approximately 20% of the previously used daily dose of levodopa.

People who took levodopa in the amount of 1500+ mg should initially take Nakom in the amount of 250/25 mg 3-4 times a day.

In maintenance therapy, the dosage may be increased by 0.5-1 tablet daily (or every other day), if necessary, until the maximum permitted daily dose (8 tablets) is reached. There is only limited information on the use of carbidopa in a daily dose exceeding 200 mg.

The maximum recommended dosage is 8 tablets of the drug per day (2 g of levodopa and 0.2 g of carbidopa). This is approximately 3 mg of carbidopa and 30 mg of levodopa per 1 kg (for a patient weighing 70 kg).

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Use Nakoma during pregnancy

There is no information on the effect of the drug when used by pregnant women. It should be taken into account that the combination of carbidopa with levodopa leads to skeletal and visceral changes in the body of animals. As a result, it is recommended to use the drug only when the possible benefit to the woman exceeds the possibility of developing a negative reaction in the fetus.

There is no information on the excretion of active components into breast milk. There is a single report of the excretion of levodopa with milk in a lactating woman with shaking palsy. Because of this, since the drug can negatively affect the baby, it is necessary to make a decision on whether to stop breastfeeding or use Nakom, also taking into account the importance of using the drug for the health of the woman.

Contraindications

Among the contraindications of the drug:

• intolerance to any of the components of the drug;
• combined use with non-selective MAO inhibitors (use of these drugs should be discontinued at least 2 weeks before the start of treatment with Nacom);
• closed-angle glaucoma;
• existing melanoma or suspicion of its presence;
• skin diseases of unknown origin.

Caution in selecting dosages, as well as monitoring the safety of the treatment course, is necessary in the following cases:

• history of myocardial infarction with rhythm disorders;
• heart failure and other severe pathologies in the cardiovascular system;
• severe forms of pulmonary pathologies (including bronchial asthma);
• epileptic seizures and other forms of convulsive attacks (history);
• the presence of erosive and ulcerative lesions in the gastrointestinal tract (since bleeding may begin in the upper gastrointestinal tract);
• the presence of diabetes mellitus and other decompensated forms of endocrine pathologies;
• severe liver or kidney failure;
• open-angle glaucoma.

Since there is no information on the safety of using the drug in children and adolescents under 18 years of age, the use of the drug for the described category of patients is prohibited.

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Side effects Nakoma

The use of the drug often leads to the development of dyskinesias (including dystonic or choreic), as well as other involuntary movements and nausea. Earlier symptoms that may contribute to the decision to reduce the dosage are considered to be blepharospasms and muscle twitching. Among other side effects:

• general: pain in the sternum, development of anorexia and syncope;
• cardiovascular system organs: development of palpitations or arrhythmia, as well as the occurrence of orthostatic effects, including a decrease or increase in blood pressure, as well as phlebitis;
• digestive system organs: the appearance of bleeding in the gastrointestinal tract, vomiting and diarrhea, as well as darkening of the color of saliva and exacerbation of ulcers in the duodenum;
• organs of the hematopoietic system: development of thrombocyto- or leukopenia, and in addition to this, agranulocytosis or anemia (also its hemolytic form);
• manifestations of allergies: the occurrence of urticaria, Quincke's edema, as well as skin itching and hemorrhagic vasculitis;
• Mental disorders and nervous system organs: development of the CNS, paresthesia, drowsiness and dizziness. In addition, manifestations of bradykinesia (development of on-off syndrome), manifestation of individual psychotic states (including hallucinations with illusions, as well as paranoid thoughts), depression (with or without suicidal thoughts), sleep problems, a feeling of excitement, dementia, increased libido and development of confusion. Occasionally, convulsions were observed, but in this case it was not possible to establish a causal relationship with the use of the drug;
• respiratory organs: development of shortness of breath;
• skin: rashes, baldness, darkening of the color of sweat gland secretions;
• urogenital system organs: darkening of urine color.

Also, side effects caused by the use of levodopa should be taken into account, as they can also occur when using Nacom:

• Gastrointestinal organs: development of dysphagia, ptyalism, bruxism, and also hiccups and bloating with constipation. There may also be a feeling of bitterness in the mouth or dryness of the oral mucosa, a feeling of discomfort in the abdomen or abdominal pain, a burning sensation in the tongue, and in addition, dyspeptic phenomena may occur;
• metabolic processes: the appearance of swelling, weight gain or loss;
• CNS organs: the appearance of a feeling of anxiety, fatigue, weakness, disorientation, and numbness. In addition, headaches, fainting, muscle cramps, asthenia, and ataxia may occur. Insomnia, euphoria, trismus, a feeling of psychomotor agitation may develop, and in addition, tremors in the arms may increase, mental activity may deteriorate, gait instability may appear, and latent oculosympathetic syndrome may be activated;
• sensory organs: development of diplopia, mydriasis, tonic spasms of gaze and visual blurring;
• urogenital system: urinary retention or, conversely, incontinence and development of priapism;
• other manifestations of disorders: development of malaise, malignant tumors on the skin, shortness of breath, hoarseness of the voice, and in addition, a rush of blood to certain areas of the skin - to the sternum, neck or face;
• laboratory test data: increased activity of ALT with AST, as well as alkaline phosphatase and LDH, and in addition bilirubin and urea nitrogen levels in plasma, the development of hyperuricemia or hypercreatininemia and a positive Coombs test result. There were also reports of decreased hematocrit values with hemoglobin, and in addition the development of bacteriuria, leukocytosis and erythrocyturia.

Medicines that contain both levodopa and carbidopa can cause a false positive response to the presence of ketone bodies in the urine (in cases where special test strips are used to detect ketonuria). This result will remain unchanged even after the procedure of boiling the samples taken. To obtain a false negative response, it is necessary to use the glucose oxidase method for detecting glucosuria.

Overdose

In case of overdose, the severity of side effects increases.

To get rid of the disorders, careful monitoring of the patient will be required, as well as ECG monitoring to be able to detect the development of arrhythmia. If necessary, the required antiarrhythmic treatment should be performed. It is also necessary to take into account that the patient could have taken other drugs along with Nakom.

Interactions with other drugs

It is necessary to combine Nakom with the following medications with caution:

Antihypertensives – in individuals taking such medications, the addition of Nacom to the combination has caused postural hypotension (symptomatic). Because of this, at the early stage of using Nacom, it may be necessary to adjust the dosage of the antihypertensive drug.

Antidepressants - a combination of levodopa and MAO inhibitors (except for MAO B type drugs) can lead to a disorder of the circulatory process, in connection with which it is necessary to stop using inhibitors 2 weeks before starting to take Nacom. This disorder occurs due to the accumulation of dopamine with norepinephrine under the influence of levodopa - their inactivation is slowed down by MAO inhibitors. As a result, the risk of tachycardia and a feeling of excitement increases, as well as dizziness, facial flushing and increased blood pressure.

There are isolated reports of side effects developing, including dyskinesia and increased blood pressure, when combining the drug with tricyclics.

Iron medications - the bioavailability of levodopa or carbidopa is reduced when used in combination with ferrous gluconate/sulphate.

Other medications – when combining levodopa with ditilin, β-adrenergic stimulants, and also with drugs used in inhalation anesthesia, the likelihood of heart rhythm disturbances may increase.

Dopamine D2 receptor antagonists (including risperidone, phenothiazines, and butyrophenones), as well as isoniazid, are capable of weakening the medicinal effect of levodopa.

There is evidence of blocking the positive medicinal effect of levodopa in shaking palsy due to combination with papaverine and phenytoin. It is necessary to carefully monitor the condition of people using these drugs in combination - in order to promptly detect a weakening of the medicinal effect.

Lithium drugs increase the likelihood of hallucinations or dyskinesias. Increased side effects are observed when combined with methyldopa, and a combination with tubocurarine increases the possibility of lowering blood pressure.

Impaired absorption of levodopa may occur in people on a high-protein diet because levodopa competes with certain amino acids.

The effect of pyridoxine (acceleration of the process of metabolism of levodopa into dopamine within peripheral tissues) may be impaired by carbidopa.

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Storage conditions

The medicine should be kept in a place protected from light and moisture, and inaccessible to children. Temperature conditions – no more than 25 °C.

Shelf life

Nakom is permitted to be taken for a period of 3 years from the date of manufacture of the drug.