After ingestion healthy persons and patients with Parkinson’s disease of a single dose of carbidopa maximum concentration (C max ) is determined in blood plasma within 2-4 hours after administration and in healthy people 1.5-5 h in patients with Parkinson’s disease. Elimination of the drug by the kidneys and intestines is approximately the same in both groups. Isolation carbidopa intact kidney is fully complete after 7 hours. Urine analysis showed the presence of only metabolites carbidopa traces of hydrazine were observed. The content of each of these substances is not more than 5% of the total metabolites.
The urine is also found in non-carbidopa modified form. The conjugates are not revealed. The presence of food in the stomach delays testosterone enanthate results absorption. Some food amino acids can compete with levodopa for absorption from the intestine and transport through the blood-brain barrier. In a large quantity in the small intestine, liver and kidney, only about 1-3% enters the brain. The excreted by the kidneys unchanged (35% for 7 hours) and in the intestine. The half-life (T 1/2 ) of blood plasma levodopa is about 50 minutes, for administration in conjunction with carbidopa -. About 2 hours metabolized in all tissues, mainly by decarboxylation with formation of dopamine which does not penetrate the blood-brain barrier, metabolites – dopamine, norepinephrine, epinephrine – rapidly cleared by the kidneys. L-dopa is metabolized to also dihydroxyphenylacetic acid, homovanillic acid (3-methoxy-4-hydroxyphenylacetic acid) and vanillylmandelic acid (hydroxy (4-hydroxy-3-methoxyphenyl) acetic acid). Trace amounts of 3-O-methyldopa were detected in plasma and cerebrospinal fluid.
The effect on the metabolism of levodopa carbidopa. Compared with placebo in healthy humans increases the concentration of levodopa carbidopa plasma statistically significant values. Similar results were demonstrated when receiving carbidopa before taking levodopa, and while receiving the two substances. In one study, pretreatment with carbidopa increases the concentration in the blood of a single dose of levodopa plasma is approximately 5 times, the period when the plasma concentration is still possible to determine increases from 4 to 8 hours. by simultaneous administration of both substances, similar results were obtained in other studies. it has been shown that patients with Parkinson’s disease, previously received carbidopa administered singly testosterone enanthate for sale labeled levodopa plasma half-life blood of all metabolites formed from radiolabeled labeled levodopa increases from 3 hours to 15 hours. The proportion of radiolabeled levodopa contained in intact levodopa increases, at least 3 times during the reception of carbidopa. After preliminary receiving carbidopa concentrations of dopamine and homovanillic acid in blood plasma is reduced.
• hypersensitivity to the drug;
• concomitant use of non-selective monoamine oxidase inhibitors (MAOIs);
• an interval of less than two weeks after discontinuation of MAO inhibitors;
• angle-closure glaucoma;
• melanoma or suspected it;
• skin disease of unknown etiology;
• the age of 18 years ( safety of the drug in children younger and middle age has not been established);
• myocardial infarction, rhythm disorders (in history);
• chronic heart failure and other severe diseases of the cardiovascular system;
• severe lung disease, including asthma;
• epilepsy and other seizures (in history);
• erosive and ulcerative lesions of the gastrointestinal -kishechnogo tract (risk of bleeding from the upper gastrointestinal tract);
• diabetes and other endocrine decompensated disease;
• severe renal and / or hepatic impairment;
• open-angle glaucoma;
• extrapyramidal reactions caused by the use of the drug;
Application of pregnancy and during breastfeeding
Because of the effect of the drug on the course of pregnancy in humans is unknown, but in rabbits a combination of levodopa with carbidopa may cause disruption of the internal organs and skeleton, the use of lac preparation ® during pregnancy is possible only if the expected benefit to the mother outweighs the potential risk to the fetus .
It is not known whether the stand with the mother’s milk of levodopa and carbidopa, so when administering the drug-lac ® during lactation should decide the issue of termination of breastfeeding.
Dosing and Administration
The dosage should be individualized for each patient, which may require dose adjustment of both the individual and the frequency of dosing. Form tablets allows to divide it into two parts with minimal effort.
The initial daily dose of 2.1 (half) of the tablet 1 or 2 times per day. However, this can not be achieved the optimal amount of carbidopa needed for many patients. If necessary, add 1/2 tablet every day or every other day until the optimum effect. The effect has been observed for the first night, sometimes after one dose. The overall effect of the drug is achieved within the period up to seven days.
The studies revealed that saturating aromatic decarboxylases peripheral 1 is achieved by introducing amino acids 70-100 mg of carbidopa per day.
If the patient receives a lower dose of carbidopa likelihood of nausea and vomiting above.
In appointing can continue to receive the standard of anti-inflammatory drugs (except levodopa monotherapy), requiring dose adjustment.
Switching from levodopa. receiving levodopa should be discontinued at least 12 hours before the start of treatment (for 24 h – in the case of long-acting formulations of levodopa). The daily dose of the should provide about 20% of the previous daily dosage of levodopa. For patients taking more than 1500 mg of levodopa, the initial dose of the is 25/250 mg 3 or 4 times a day.
Maintenance treatment. If necessary, the can be increased to 1 tablet every day or every other day to a maximum dose – 8 tablets per day. Experience receiving a daily dose of carbidopa in excess of 200 mg is limited.
The maximum recommended dose of eight tablets lac preparation ®per day (200 mg carbidopa and 2000 mg of levodopa), which corresponds to about 3 mg / kg carbidopa and 30 mg / kg of levodopa per kilogram of the body of the patient with a body weight of 70 kg. elderly patients: there is a great experience with levodopa and carbidopa in elderly patients. No dose adjustment is required.
Patients with renal / hepatic impairment: dose adjustment is required.
According to the World Health Organization (WHO), undesirable effects are classified according to their rate of development as follows: very common (≥1 / 10), commonly (≥1 / 100, <1/10), uncommon (≥1 / 1000, < 1/100), rare (≥1 / 10,000, <1/1000) and very rare (<1/10000); the frequency is unknown – the frequency of events can not be determined on the basis of the available data.
The most common adverse effects are dyskinesias including choreiform, dystonic, and other involuntary movements and nausea. Early signs, on the basis of which it may be decided to reduce the dose, can be considered as muscle twitching and blepharospasm.
Benign, malignant and unspecified neoplasms, including cysts and polyps frequency is unknown: malignant melanoma.
From the side of hematopoiesis rare: leukopenia, anemia (including .. .ch haemolytic), thrombocytopenia, agranulocytosis immune system rarely angioedema.
Metabolism common: anorexia frequency not known: loss or weight gain, edema.
On the part of the psyche often: sleep disturbances, including nightmares, hallucinations , depression (including suicidal intent), confusion; rare: agitation, rarely . psychotic reactions, including delusions and paranoid thinking, increase libido in patients receiving dopamine antagonists, there are pathological gambling, hypersexuality, compulsive waste (craving for shopping), binge eating and overeating, increased libido. The testosterone enanthate results above reaction basically disappeared after dose reduction or discontinuation of treatment.
Frequency not known: anxiety, disorientation, euphoria, insomnia, bruxism.
The nervous system is very common: dyskinesia, including chorea, dystonia and other involuntary movements, often: episodes of bradykinesia ( «on-off» -sindrom), dizziness, paresthesia, drowsiness, including less daytime sleepiness and episodes of sudden sleep; rare: syncope; rare: dementia, convulsions; the frequency is not known: ataxia, tremor, ekstrapramidnye disorders, neuroleptic malignant syndrome , muscle twitching, headache, decreased visual intelligence, trismus, activation of latent syndrome Bernard-Horner, insomnia, nervousness, euphoria, numbness, fainting, falling, gait disturbance, feeling of irritation, compulsions. reported seizures develop, but a causal relationship with reception lac preparation ® . Not installed from the senses the frequency is unknown: blepharospasm, diplopia, blurred vision, dilated pupils, oculogyric crises (tonic convulsions external muscles of the eyeball).
On the part of the cardiovascular system often: palpitations, orthostatic reactions, including episodes lowering blood pressure; rare: arrhythmia, phlebitis, increased blood pressure, the frequency is not known: flushing, flushing.
The respiratory system is often: shortness of breath; the frequency is unknown: hoarseness, abnormal breathing patterns.
On the part of the gastrointestinal tract common: vomiting, diarrhea, rarely : gastrointestinal bleeding, worsening of duodenal ulcers, dark saliva, the frequency is unknown:dryness of the oral mucosa, salivation, dysphagia, abdominal pain, constipation, flatulence, dyspepsia, burning sensation tongue, bitterness in the mouth, nausea, . belching part of the skin uncommon:urticaria rare: pruritus, hemorrhagic vasculitis (Henoch-Schonlein purpura), alopecia, rash, dark sweat, the frequency is not known: excessive sweating.
From the urinary system rare: darkening of the urine.frequency not known: urinary incontinence ., urinary retention
On the part of the musculoskeletal and connective tissue uncommon: muscle cramps; frequency not known: muscle twitching.
Reproductive system frequency is not known: priapism.
General disorders and injection site common: chest pain; the frequency is unknown: asthenia , swelling, weakness, malaise, fatigue, neuroleptic malignant syndrome.
Laboratory findings frequency is unknown: increased activity of alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, increased bilirubin, urea nitrogen in the blood plasma, urea in blood plasma, hypercreatininemia, hyperuricemia, positive Coombs test. It has been reported to reduce levels of hemoglobin and hematocrit, hyperglycemia, leukocytosis, bacteriuria, hematuria. Preparations containing carbidopa and levodopa, may cause a false positive reaction for ketones in the urine, if the test strips are used to determine ketonuria. This reaction is not changed by boiling the urine sample. False negative results can be obtained using the glucose oxidase method for determining glycosuria.
In case of overdose amplified the severity of the symptoms listed in the “side effects”.
Treatment: gastric lavage, activated charcoal; should ensure careful monitoring and electrocardiographic monitoring for timely detection of arrhythmias, adequate antiarrhythmic therapy should be carried out if necessary. Measures in case of acute overdose of the drug-lac ® is basically the same as that of an acute overdose of levodopa. Note that pyridoxine is not effective for the removal of the drug action Nak ® . You must also take into account the concomitant therapy that the patient is receiving along with drug-lac ® .
Interaction with other drugs
In an application with antihypertensive agents is necessary to adjust the dose of the latter because of the risk of orthostatic hypotension.
In the simultaneous use of levodopa with inhibitors of monoamine oxidase (MAO) (except MAO-B inhibitors) are possible circulatory disorders (MAO inhibitors should be discontinued at least for 2 weeks prior to the administration of the drug). This is due to the accumulation of levodopa under the influence of dopamine and norepinephrine, which inhibited inactivation of MAO inhibitors, and a high probability of excitation, high blood pressure (BP), tachycardia, facial flushing and dizziness. Iron salts may reduce the bioavailability of levodopa and carbidopa; the clinical significance of this interaction is unknown. With the simultaneous use of levodopa with β-agonists, ditilinom and drugs for inhalation anesthesia may increase the risk of cardiac arrhythmias. antagonists of D 2 dopamine receptors (eg, derivatives of butyrophenone, difenilbutilpiperidina, thioxanthenes, phenothiazines, risperidone) and isoniazid reduce the therapeutic effect of levodopa. There are reports of blocking the positive therapeutic effects of levodopa as a result of receiving phenytoin and papaverine. lithium drugs increase the risk of developing dyskinesia and hallucinations. methyldopa increases the side effects. Concomitant use oftubocurarine increases the risk of hypotension. The absorption of levodopa can be impaired in patients who are on a diet with a high content of protein as levodopa competes with certain amino acids.Carbidopa inhibits the action of pyridoxine hydrochloride (vitamin B 6 ), which accelerates the metabolism of levodopa to dopamine in peripheral tissues.
Nak ® can be given to patients who are already taking levodopa monotherapy. However, levodopa in a single component form should be stopped at least 12 hours before the appointment lac preparation ®.
Patients who had previously received only levodopa may occur dyskinesia as carbidopa provides a more effective penetration of levodopa in the brain and, therefore, is formed greater dopamine. In the event of dyskinesias may require dose reduction.
As with levodopa, levodopa / carbidopa may cause involuntary movements and mental disturbances. It is believed that these responses are associated with increased levels of dopamine in the brain after administration of levodopa and levodopa use / carbidopa can cause relapse. It may require dose reduction.
All patients should testosterone enanthate results be monitored carefully for the development of depression with concomitant suicidal tendencies.
In the treatment of patients who have previously observed or current symptoms of psychosis observed, precautions must be taken.
Caution should be exercised with concomitant administration of psychoactive drugs and levodopa / carbidopa). An early sign of excess dosage in some patients can serve as blepharospasm.
As in the cases of levodopa, in appointing a drug-lac ® to patients who have suffered a myocardial infarction and have a history of atrial, nodal or ventricular arrhythmia, should be closely preliminary examination.
Therefore patients are advised to conduct regular cardiological survey, in particular, the appointment of the first dose and during the selection of doses.
Levodopa / carbidopa should be used with caution in patients with severe cardiovascular or pulmonary disease, asthma, kidney disease, liver, endocrine diseases or in the presence of indications of peptic ulcer disease (because of the possibility of gastrointestinal bleeding from the upper gastrointestinal tract) or seizures in history.
In patients with open-angle glaucoma in patients receiving drug-lac ® is necessary to monitor intraocular pressure regularly.
The reception of MAO inhibitors should be discontinued at least two weeks before beginning treatment with Nak ® .
With the sudden cancellation of anti-Parkinsonian drugs may develop symptom complex resembling neuroleptic malignant syndrome (muscular rigidity, increased body temperature, mental disorders and an increased concentration of serum creatinine phosphokinase). It is necessary to carefully examine the patient during the period of sharp decline in dose-lac ® or cancel it, especially if the patient is receiving anti-psychotic drugs.
Levodopa accompanied by sleepiness and episodes of sudden sleep.
Very rarely reported cases of sudden sleep during daily activities, in some cases without awareness or warning signs.
If you notice any of these symptoms it is recommended to consider the possibility of reducing the dose.
You should periodically conduct a blood test, with long-term therapy is recommended periodic monitoring of the cardiovascular system, liver and kidneys.
If general anesthesia is required, lac ® can be taken until until the patient is allowed ingestion of the drug. If therapy is interrupted temporarily, the usual dose can be appointed again as soon as the patient is able again to take the drug orally.
Studies have shown that patients with Parkinson’s disease are at increased risk of developing melanoma, so patients taking lac ® , you must have regular inspections at dermatologist.
Do not clear whether the increased risk of Parkinson’s disease or other factors, such as drugs used to treat Parkinson’s disease.
in patients receiving dopamine antagonists, there are pathological gambling, hypersexuality, compulsive waste (craving for shopping) gluttony and overeating, increased libido. With the development of the above symptoms it is recommended doses / correction of treatment.
Lac ® is not recommended for the treatment of extrapyramidal disorders caused by medications.
Foods high in protein may interfere with the absorption of the drug.
Effects on ability to drive vehicles, machinery
In very rare cases, levodopa may cause drowsiness and cases of sudden sleep onset. During treatment with lac ® should inform patients about the possibility of sudden sleep. Patients with sleepiness and experience sudden falling asleep (cases of sudden sleep) should refrain from driving motor vehicles and activities potentially hazardous activities that require high concentration and psychomotor speed reactions. buy testosterone geneza pharmacueticals buy anabolic steroid online