The volume of distribution – 1.6 l / kg.Carbidopa with levodopa compared absorbed and absorbed more slowly. Associated with the plasma protein by about 36%. Individual carbidopa bioavailability is 40-70%. Entacapone dianabol cycle is rapidly absorbed from the gastrointestinal tract. It binds to plasma proteins to 98%, mostly to albumin; at therapeutic concentrations does not displace from its association with other protein drugs with a high degree komplekssobrazovaniya (warfarin, salicylic acid, phenylbutazone, diazepam, etc.). Individual bioavailability of 35% (at a single oral 200 mg). The maximum concentration after a single ingestion is achieved after 1 h. The volume of distribution of 0.27 l / kg.
Metabolism and excretion. Levodopa is extensively metabolised in all tissues using dopa decarboxylase, and dianabol cycle to dopamine, norepinephrine, epinephrine, and . 75% of the dose excreted by the kidneys as metabolites for 8 hours. The unaltered excreted by the kidneys (35% to 7 hours), and intestine. The total clearance of levodopa 0,55-1,38 l / kg / h. Carbidopa is metabolized to two main metabolites which are excreted in the urine as the glucuronide and unbound structures. Carbidopa unchanged at 30% is excreted by the kidneys in the urine. Among the metabolites excreted in the urine dianabol sale, the main ones are: acid and alpha-methyl-3,4-digidroksifenilpropionovaya acid. It has the effect of “first pass” through the liver, a small amount of entacapone, which is (E) -isomer is converted to (Z) -izomep (approximately 5% of the total amount of entacapone in blood plasma). Excreted by the kidneys by 10% -20%, and through the intestine (in the feces and bile) by 80-90%.
The main pathway of entacapone and dianabol cycle its active metabolite – conjugation with glucuronic acid. The total clearance is about 0.7 L / kg / h. The half-life of 0.4-0.7 h.Due to the short half-life when reappointment is no true accumulation of levodopa or entacapone. The age group of patients. The pharmacokinetic parameters in younger patients (45-64 years) and older (65-75 years) age groups are the same. Paul. Bioavailability of levodopa is significantly higher in women. The bioavailability of carbidopa and entacapone does not depend on the sex of the patient. Abnormal liver function. The metabolism of entacapone is slowed in patients with mild to moderate hepatic impairment (classes A and B according to Child-Pugh classification), which leads to an increase of entacapone plasma concentrations in the absorption phase, as well as in the elimination phase. Renal impairment. It does not affect the pharmacokinetics of entacapone. Research pharmacokinetics of levodopa and carbidopa in patients with impaired renal function have not been conducted.
Indications for use . Parkinson’s disease and parkinsonism dianabol cycle (except medicinal) in cases where use of a combination of Levodopa + Carbidopa ineffective.
- hypersensitivity to the active ingredients or to any of the excipients (fillers);
- expressed human liver;
- narrow-angle glaucoma;
- combined use with a non-selective inhibitors of monoamine oxidase (MAO) type A and B (such as phenelzine, tranylcypromine);
- combined use with selective inhibitors of MAO-A and MAO-B;
- neuroleptic malignant syndrome, and / or atraumatic acute rhabdomyolysis (including history).
- age of 18 years;
- pregnancy, except in individual cases where the potential benefit from taking Stalevo than the potential risk for the development of the fetus.Precautions : severe cardiovascular and pulmonary insufficiency, asthma, liver disease, kidney; diabetes and other decompensated endocrine disease, erosive and ulcerative lesions gastrointestinal tract; seizures (in history), history of myocardial infarction (with residual atrial nodal or ventricular arrhythmias) – requires monitoring of cardiac function throughout the period of the initial regulation of the drug dosage; psychosis in the anamnesis and / or during the treatment of depression dianabol dose with suicidal tendencies, antisocial behavior ; wide-angle glaucoma – with careful monitoring of intraocular pressure, patients receiving during treatment with Stalevo drugs that can cause orthostatic hypotension; when concomitant administration of antipsychotic agents that block dopamine (particularly D2 receptor antagonists), treatment with Stalevo should be carried out under the close supervision of the patient for termination antiparkinsonian effect of the drug or enhancing disease symptoms; Simultaneous treatment Stalevo and tricyclic antidepressants desipramine, maprolitina, venlafaxine. Simultaneous treatment with warfarin and drugs metabolized by dianabol cycle(paroxetine).
Dosage and administration . Inside, regardless of meals, without dividing it into pieces. The optimum daily dose is determined by the careful selection of levodopa dose for each patient individually. The daily dose is preferably optimized using one of the three existing kinds of Stalevo dosage (50 / 12.5 / 200 mg, or 150 mg 100/25/200 / 37.5 / 200 mg levodopa / carbidopa / entacapone). In only one dosage any pill should be taken as a single dose. The maximum daily dose -. 1.5 g of levodopa, 2 g of entacapone, 375 mg carbidopa (equivalent to 10 tablets of Stalevo 150 / 37.5 / 200 mg) dose control in the course of treatment . If necessary, the introduction of more levodopa reduce the interval between doses of the drug and / or translate the patient on treatment Stalevo a greater dosage (required within the recommended dose!). If you need a smaller amount of levodopa, it increases the intervals between doses of the drug and / or translate the patient on treatment Stalevo a lesser dosage. If simultaneously with Stalevo other drugs used containing levodopa, you should carefully follow recommendations for total daily dose of the drug.
Side effects: Nervous system disorders: ataxia, numbness, trismus, activation of latent Horner’s syndrome, dyskinesia (including horeimorfnye, dystonic, and other involuntary movements), hyperkinesia, bradykinesia (the phenomenon of “switch – off”), worsening of Parkinson’s symptoms, blepharospasm, bruxism; drowsiness, dizziness, anorexia. Psychiatric disorders: confusion, insomnia, paroniriya, nightmares, hallucinations, agitation, anxiety, euphoria; changes in thinking (including paranoid thinking and transient psychosis); depression with the development of suicidal tendencies or without; cognitive dysfunction, Cardiovascular system: arrhythmia, orthostatic hypotension, hypertension, phlebitis. The bodies of: diplopia, blurred vision, dilated pupils, oculogyric crises. Disorders of the digestive system:dry mouth, bitter taste in the mouth, nausea, vomiting, drooling, dysphagia, hiccups, pain and discomfort in the stomach, constipation, diarrhea, flatulence, burning sensation on the tongue, gastrointestinal bleeding, development of duodenal ulcer; hepatitis. Skin reactions: flushing of the skin, a feeling of “tides” of blood, rash, changes in perspiration color (browning), hair loss, erythematous or makulopodobnye rash, urticaria. Disorders of the urinary system: urinary retention, urinary incontinence, discoloration of urine, priapism. Respiratory system: chest pain, dyspnoea. hematopoietic system: hemolytic and non-hemolytic anemia, thrombocytopenia, agranulocytosis. Other: weakness, fatigue, headache, hoarseness, malignant melanoma.
Overdosing Symptoms: increased severity of side effects. Treatment: hospitalization, gastric lavage, repeated administration of activated charcoal. Monitoring of respiratory function, cardiovascular and urinary systems; ECG monitoring if necessary -. Antiarrhythmic therapy pyridoxine is not effective in overdose Stalevo.
Interaction with other medicinal products Other antiparkinsonian agents. Therapy Stalevo does not preclude the application of other antiparkinsonian drugs. The daily dose seleginina while taking a drug Stalevo should not exceed 10 mg. Antidepressants. Stalevo is compatible with imipramine and moclobemide. The therapeutic effect of Stalevo is reduced while admission to antagonize dopamine receptors (some antipsychotics and antiemetics), phenytoin, papaverine. The therapeutic effect of Stalevo may be reduced in patients receiving high-protein diet, due to competitive action of levodopa and some amino acids. in simultaneous reception with iron supplementation is necessary to observe a time interval of 2-3 hours between taking Stalevo and iron-containing drugs (levodopa and entacapone in the gastrointestinal tract to form chelates with iron ions). Stalevo is compatible with the preparations of vitamin B6 (pyridoxine hydrochloride), diazepam, ibuprofen.
Cautions When replacing Stalevo therapy to levodopa + carbidopa (without entacapone) – need to increase the dose of levodopa. Entacapone in combination with levodopa may cause drowsiness and occasional instant sleep. It is necessary to abandon the car and working with machines and mechanisms driving. Stalevo is not assigned to eliminate extrapyramidal reactions caused by taking drugs. Before the planned general anesthesia drug can take as long as the patient oral administration is allowed. In case of long-term treatment Stalevo is required periodic monitoring liver, hematopoietic, kidney, cardiovascular system. Abolition Stalevo performed dianabol cycle slowly increasing the dose of levodopa as needed.
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