Carbidopa, levodopa

Pharmacological properties

carbidopa and levodopa teva is a combined antiparkinsonian drug containing the metabolic precursor of dopamine - levodopa and a peripheral dopadecarboxylase inhibitor - carbidopa.

Parkinsons symptoms are thought to be associated with insufficient dopamine. Normally, dopamine acts as a neurotransmitter and is synthesized in certain brain cells that control muscle activity. Movement disorders are considered a consequence of dopamine deficiency.

The anti-Parkinsonian effect of levodopa is due to its conversion to dopamine by decarboxylation directly in the central nervous system, which leads to the completion of dopamine deficiency in nerve cells.

Carbidopa does not penetrate the BBB and prevents extracerebral decarboxylation of levodopa, due to which the influx of levodopa into the brain and its conversion to dopamine in the central nervous system increases, which leads to a decrease in the severity of symptoms of Parkinsons disease in many patients.

Pharmacokinetics Levodopa and carbidopa are well absorbed, C_max drug in blood plasma is achieved after 1-3 hours. T_½ levodopa is about 2 hours in the presence of carbidopa. As a result of the action of carbidopa, the excretion of levodopa from blood plasma is reduced by 50%. In the presence of carbidopa, levodopa is mainly metabolized to amino acids and in a small amount to catecholamine derivatives. All metabolites of carbidopa and levodopa are excreted in the urine.

Indications

Parkinsons disease and syndrome.

Application

The tablet has a dividing line, that is, the tablet can be divided in half.

The optimal daily dose of carbidopa / levodopa is determined by careful titration individually for each patient.

Depending on the severity of the disease, it may take about 6 months to achieve the optimal therapeutic effect.

Patients not taking levodopa. For patients starting to take the drug, the initial dose is ½ tablet 1-2 times a day. If necessary, you can add another ½ tablets every subsequent day until the required dose of carbidopa is reached.

The therapeutic effect of the drug appears on the same day, sometimes after a single dose. A full effective dose of the drug is achieved over 7 days compared to the weeks and months of levodopa alone.

Patients taking levodopa. Levodopa administration should be stopped at least 12 hours (24 hours for slow-release dosage forms) before starting treatment with Carbidopa and Levodopa-Teva. Usually the drug is taken in the morning, while at night, levodopa is not used. The dose should be about 20% of the previous daily dose of levodopa.

Initial dose. Patients taking 1500 mg of levodopa per day: the initial daily dose should be 75-100 mg of carbidopa and 300-400 mg of levodopa (use a drug with a dosage of carbidopa / levodopa in a ratio of 1: 4), divided into 3-4 doses. Patients taking 1500 mg of levodopa per day: the initial dose of the drug is 1 tablet 3-4 times a day.

Maintenance dose. During therapy with Carbidopa and Levodopa-Teva, individual characteristics of the patient should be taken into account, the dosage should be gradually changed depending on the therapeutic effect.

If you need to use levodopa in a higher dose, the dose of the drug can be increased to 1 tablet 3-4 times a day. If necessary, the dose can be increased by ½ – 1 tablet every day (maximum daily dose - 8 tablets).

If the patient is transferred to the drug Carbidopa and Levodopa-Teva from levodopa in combination with other decarboxylase inhibitors, the use of drugs should be stopped at least 12 hours before the start of the drug Carbidopa and Levodopa-Teva.The use of the drug begins with a dose equivalent to the amount of levodopa / decarboxylase inhibitor in previous preparations.

Patients taking other antiparkinsonian drugs. The combination of the drug with MAO-B inhibitors can increase the effectiveness of the drug Carbidopa and Levodopa-Teva in controlled cases of akinesia and / or dyskinesia. The use of other standard antiparkinsonian drugs (except for levodopa) can be continued with the appointment of carbidopa and levodopa, although the dose of these drugs or the dose of levodopa must be changed.

Elderly patients. The drug is prescribed to the elderly.

Contraindications

Hypersensitivity to the active components or to any of the components of the drug; glaucoma; severe heart failure; severe cardiac arrhythmia; severe psychosis; simultaneous use of selective MAO type a inhibitors and non-selective MAO inhibitors (with the exception of individual MAO-b inhibitors in low doses). these drugs must be discontinued at least 2 weeks before the appointment of carbidopa and levodopa-teva; Suspicious and undiagnosed skin diseases or a history of melanoma.

The drug is not used in patients for whom sympathomimetics are contraindicated.

Side effects

Side effects that occur when using the drug are often associated with the neuropharmacological effect of dopamine. usually these reactions are eliminated or their severity decreases with a decrease in dose. the most common are cases of dyskinesia, including choreo-like, dystonic and other involuntary movements. the development of muscle spasm and blepharospasm indicates that the dose should be reduced.

Other serious side effects include changes in thinking, including paranoid thinking and psychosis, depression with or without suicidal tendencies, and dementia. Cases of pathological excitement, increased libido and hypersexuality are noted, especially when using the drug in high doses; these manifestations disappeared when the dose was reduced or the drug was discontinued.

The following side effects are associated with taking levodopa and its combination.

On the part of the blood and lymphatic system: leukopenia, hemolytic and non-hemolytic anemia, thrombocytopenia, agranulocytosis.

From the immune system: hypersensitivity reactions, including angioedema, urticaria.

From the cardiovascular system: palpitation, cardiac arrhythmias, orthostatic effects, including arterial hypotension, tendency to loss of consciousness, fainting, hypertension, phlebitis.

From the side of the nervous system: dizziness, bradykinesia, the on-off phenomenon (can occur after several months or even years from the start of treatment with levodopa and is probably associated with the progression of the disease (in such cases, dose and interval adjustment between them may be required)) , ataxia, dyskinesia, chorea, dystonia, extrapyramidal and motor disorders, bradykinesia, increased hand tremor, muscle twitching, muscle cramps, trismus, paresthesia, falling, gait disturbance, malignant antipsychotic syndrome m, convulsions, tendency to fainting, loss of consciousness, activation of the hidden Bernard-Horner syndrome.

On the mental side: confusion, insomnia, nightmares, mania, dizziness, exhaustion, depression, suicide attempts, euphoria, dementia, change in mental status (including paranoid thoughts and transient psychosis), hallucinations, delirium, agitation, anxiety, agitation, fear , fall, impaired gait, impaired thinking, disorientation, headache, numbness, cramps, drowsiness, sudden bouts of drowsiness.

From the digestive system: dyspepsia, nausea, vomiting, dry mouth, bitter taste in the mouth, hypersalivation, dysphagia, bruxism, hiccups, abdominal pain, constipation, diarrhea, flatulence, dyspepsia, gastrointestinal pain, glossalgia, dark coloration of saliva bleeding, burning sensation on the tongue, duodenal ulcer, gastrointestinal bleeding.

Metabolic disease: decrease or increase in body weight, edema, anorexia.

On the part of the skin and subcutaneous tissues: itching, hyperemia, sweating, dark sweat, rash, hair loss, activation of malignant melanoma, Shenlein-Genoch disease.

From the respiratory system: chest pain, hoarseness, pain in the sternum, shortness of breath, respiratory failure.

From the musculoskeletal system: muscle spasm.

From the urinary system: urinary retention, urinary incontinence, dark urine, priapism.

From the side of the organ of vision: blurred vision, blepharospasm, activation of the latent Horner syndrome, diplopia, mydriasis, oculomotor crisis, eye spasm. Blepharospasm can be an early symptom of an overdose.

Laboratory indicators: an increase in liver function indicators, such as alkaline phosphatase, AlAT, AsAT, LDH, bilirubin, blood urea nitrogen, creatinine, uric acid, a positive Coombs test, a decrease in hemoglobin and hematocrit, an increase in blood glucose, leukocytosis, bacteriuria, hematuria.

Others: general weakness, asthenia, fatigue, poor health, sudden exacerbation of concomitant diseases, flushing, hyperemia, malignant melanoma.

Levodopa is associated with drowsiness, but cases of drowsiness during the day and sudden falling asleep in connection with taking levodopa have been very rarely reported.

Impulse control impairment: pathological gambling, increased libido, hypersexuality, impulsive desire to make a purchase, overeating, impulsive food with dopamine agonists and / or other dopamine-containing drugs, including carbidopa and levodopa.

special instructions

The drug should not be used for treatment of extrapyramidal reactions resulting from the use of drugs, and is also not recommended for the treatment of patients with huntingtons chorea.

The drug is used with caution in people with cardiovascular diseases and diseases of the kidneys, liver, respiratory tract, with BA, endocrine diseases, open-angle glaucoma, a stomach ulcer and / or duodenal ulcer (due to the likelihood of bleeding from the upper digestive tract ), hemathemesis, Cushings syndrome, mental disorders, history of seizures.

The initial dose for patients with myocardial infarction, atrial, nodular and ventricular arrhythmias is prescribed if the patient is under constant medical supervision and his cardiac function is monitored.

If it is necessary to carry out the operation under anesthesia, the drug is canceled the day before. The use of the drug is resumed after surgery, as soon as the patient can take it.

All patients using the drug should be closely monitored to detect mental changes, depressive syndrome with concomitant suicidal intentions. Patients with psychosis (including a history) require special attention. With an increase in psychotic symptoms, Carbidopa and Levodopa-Teva must be canceled.

In patients who were previously treated only with levodopa, dyskinesia is possible, since carbidopa allows more levodopa to reach the brain and, thus, more dopamine is formed. The appearance of dyskinesia requires a dose reduction.

Just like levodopa, the drug can cause involuntary movements and mental disorders.Patients who had involuntary movements and psychoses in the treatment of levodopa require special attention when using the drug Carbidopa and Levodopa-Teva. Such reactions are caused by an increase in the amount of dopamine in the brain, which is a consequence of the use of levodopa, and taking Carbidopa and Levodopa-Teva can cause a relapse.

Patients with a history of orthostatic hypotension require careful monitoring, especially at the beginning of carbidopa and levodopa-Teva. Such patients may require appropriate treatment.

With a sharp cessation of taking antiparkinsonian drugs, a syndrome similar to a neuroleptic malignant syndrome is noted, including muscle rigidity, fever, mental changes and an increase in plasma CPK, especially when patients were treated with antipsychotic drugs. Therefore, it is necessary to observe patients with any abrupt cessation or change in dosage of the drug Carbidopa and Levodopa-Teva, especially those who also receive antipsychotics.

Prescribe psychoactive drugs, such as phenothiazines or butyrophenones, should be used with caution. The treatment of patients with a history of seizures requires special care.

As in the case of levodopa, periodic checks of the liver, blood, blood, cardiovascular and renal functions are required throughout the treatment.

Patients with chronic open-angle glaucoma should be prescribed with caution under the condition of constant monitoring of intraocular pressure and careful monitoring of its changes during treatment.

Levodopa can cause drowsiness and sudden episodes of drowsiness. Cases of sudden episodes of drowsiness during daytime activity are rare. However, patients should be informed about the possible occurrence of such symptoms, and if they occur, consider the possibility of reducing the dose or stopping treatment.

Impulse control impairment. Patients should be carefully monitored for impulse control impairment. Patients and their environment should be warned of possible changes in behavior that indicate impaired impulse control, such as pathological gambling, increased libido, hypersexuality, impulsive desire to make a purchase, overeating, impulsive food, when using dopamine agonists, including cabergoline. In this case, you should reduce the dose of the drug or stop its use.

Laboratory research. Typically, creatinine and urea are lower than with levodopa. Transient abnormalities include an increase in blood urea, AlAT, AsAT, LDH, bilirubin, alkaline phosphatase, protein-bound iodine.

There is a decrease in hemoglobin, hematocrit, an increase in glucose in blood plasma and white blood cells, an increase in the number of bacteria and blood in the urine.

Positive tests for erythrocyte antibodies are noted both when using Carbidopa and Levodopa-Teva, and when using only levodopa, but hemolytic anemia is practically not observed.

The drug Carbidopa and Levodopa-Teva can cause a false positive result when measuring ketones in the urine using a litmus test; this reaction does not change when boiling urine. Using methods using glucose oxidase can give a false negative result in a study on glucosuria.

In the presence of Parkinsons disease, patients have been reported to have an increased risk of developing melanoma. It is not known whether this risk is associated with Parkinsons disease or with other factors, such as the use of drugs to treat Parkinsons disease.Therefore, it is recommended to constantly monitor the condition of the skin to identify possible melanoma and periodically undergo a skin examination by a qualified specialist (for example, a dermatologist) in the treatment of Carbidopa and Levodopa-Teva.

In case of drug discontinuation, the dose is reduced gradually, while carefully monitoring the patient’s health.

Use during pregnancy and lactation. Although the effect of the drug on pregnancy is unknown, however, both levodopa and its combination with carbidopa caused malformations of the internal organs and skeleton in an animal experiment. The drug is contraindicated during pregnancy and lactation. All women of reproductive age who use carbidopa / levodopa should use effective methods of contraception.

It is not known whether carbidopa or levodopa is excreted in human milk with breast milk. To prevent the occurrence of negative reactions in children, a decision should be made: interrupt breastfeeding or stop taking the drug, given its importance to the mother.

Children. The safety of the drug for children has not been established, so it is not prescribed for patients under the age of 18 years.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Considering that in sensitive patients, when using the drug, adverse reactions (dizziness, hallucinations, uncontrolled movements, drowsiness, cases of sudden sleep, visual impairment) may occur, while taking the drug, you should refrain from driving vehicles and performing other work that requires concentration.

Interactions

It is necessary to use the drug with caution simultaneously with:

• antihypertensive drugs. In patients taking certain antihypertensive drugs, the addition of combinations of levodopa with a decarboxylase inhibitor caused the development of symptomatic orthostatic hypotension, therefore, at the beginning of treatment with the drug, there may be a need for dose adjustment of the antihypertensive drug;
• antidepressants. There are few reports of adverse reactions, including hypertension and dyskinesia, caused by the simultaneous use of tricyclic antidepressants and levodopa preparations with carbidopa. Carbidopa and Levodopa-Teva can be used only with selective MAO-B inhibitors in recommended doses (for example, selegiline);
• anesthetics. The simultaneous use of anesthetics can cause arrhythmia;
• anticholinergics. May act synergistically with levodopa in reducing tremor, and this feature is often used to enhance the therapeutic effect; however, they can sharpen involuntary movements. In high doses, they can also reduce the positive effect of levodopa by slowing its absorption, thereby increasing the gastric metabolism of the drug;
• other medicines. Phenothiazines, benzodiazepines, isoniazid, butyrophenones, phenytoin and papaverine can reduce the therapeutic effect of levodopa. Levodopa metabolism increases with the use of anticonvulsant drugs.

Given that levodopa competes with certain amino acids, some patients on a high-protein diet may experience poor absorption.

The addition of carbidopa prevents an increase in the level of levodopa metabolism in dopamine, which is caused by the action of vitamin B₆. The drug can be used in patients with parkinsonism taking vitamin preparations containing pyridoxine hydrochloride (vitamin B₆).

Combination therapy with selegiline can lead to severe orthostatic hypotension, which is not characteristic of the drug Carbidopa and Levodopa-Teva.

Iron preparations can inhibit the absorption of levodopa.

Sympathomimetics may increase the cardiovascular side effects of levodopa.

With simultaneous use with antacids, the effect on the bioavailability of levodopa has not been studied.

Together with the drug, dopamine antagonists, amantadine can be used. If these drugs are prescribed in addition to carbidopa and levodopa-Teva therapy, a dose adjustment may be required.

Metoclopramide increases the concentration of levodopa in blood plasma.

The combined use of catecholomethyl transferase inhibitors (tolcapone, entacapone) and levodopa / carbidopa can increase the bioavailability of levodopa.

It can be used with other antiparkinsonian drugs that do not contain levodopa.

Overdose

Symptoms: early signs of an overdose - heart rhythm disturbance, involuntary movements, tonic blepharospasm, muscle twitching, ag, increased heart rate, decreased appetite, confusion, anxious agitation, insomnia, anxiety.

Treatment: artificially induce vomiting, rinse the stomach immediately.

Symptomatic therapy: infusions are prescribed with caution, pay attention to the airway; when arrhythmia occurs, appropriate treatment with ECG monitoring is used. The importance of dialysis in cases of overdose has not been studied. The use of pyridoxine is ineffective.

Storage conditions

At temperatures up to 25 ° C.