Treatment of Parkinson's disease in accordance with the following principles: initial treatment as monotherapy to delay the introduction of levodopa; combined treatment with levodopa during the disease period, when the effect of levodopa extinguishes or becomes variable and there are fluctuations of the therapeutic effect (the so-called "end of dose" effect or "on-off" type fluctuations).
Nonergoline Dopamine agonist D2 / D3. It reduces the dopamine deficiency characteristic of Parkinson's disease by stimulation of dopamine receptors in the striatum. It works on the hypothalamus and pituitary gland, inhibiting the secretion of prolactin. The bioavailability of ropinirole is approximately 50% (36-57%). After oral administration of Cmax is achieved within 6-10 h. In patients receiving the drug in the form of tablets. about release, a high-fat meal may increase systemic exposure to ropinirole (increased AUC by 20% on average,max 44% on average, T-delaymax by 3 hours). Ropinirole 10-40% bound to plasma proteins. It is metabolized mainly via CYP1A2 and excreted as metabolites in the urine. T0,5 is about 6 hours. A wide interindividual variability of pharmacokinetic parameters has been observed. After administration at steady state of ropinirole in the form of about release of individual variability of Cmax was 30-55% and AUC 40-70%.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients. Severe renal impairment (creatinine clearance <30 ml / min) without regular hemodialysis. Hepatic dysfunction.
Precautions:
Dopamine agonist medicines should not be used in patients with a history of serious psychiatric or psychotic disorders or such disorders unless the potential benefit outweighs the risk. Patients should be warned about the possibility of sudden sleep attacks (in some cases unconscious or without any warning symptoms). In these patients, a dose reduction or complete termination of therapy may be considered. Patients should be monitored for impaired control over drive (including pathological gambling, increased libido and pathological sexual activity, uncontrollable willingness to spend money and make purchases, gluttony and overeating). If such symptoms occur, a dose reduction or gradual discontinuation of the drug should be considered. These disturbances were found especially in patients treated with high doses of medication and usually resolved after a dose reduction or after discontinuation of the drug. In some cases, a history of risk has occurred, such as pre-existing compulsive behaviors. Due to the risk of hypotension, a constant control of the blood pressure value is necessary, especially at the beginning of treatment and with particular emphasis on patients with severe cardiovascular disease (mainly coronary insufficiency). Cigarette smoking is a known factor inducing CYP1A2 metabolism, so if you take or stop smoking during ropinirole therapy, it may be necessary to adjust the dose again. Due to the lack of data on safety and efficacy, it is not recommended for use in children and adolescents under 18 years of age. Table. 2 mg contain lactose - should not be used in patients with rare hereditary galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption. Table. 4 mg contain sunset yellow which may cause allergic reactions.
Pregnancy and lactation:
It is not recommended during pregnancy unless the expected benefits to the patient outweigh the risks to the fetus. The drug can inhibit lactation - it should not be used during breastfeeding.
Side effects:
Side effects in patients with Parkinson's disease treated with ropinirole in the form ofprolonged release (up to 24 mg / day).monotherapy. Very often: drowsiness, nausea. Common: hallucinations, dizziness (including labyrinthine origin), constipation, peripheral edema. Uncommon: orthostatic hypotension, hypotension.Combination therapy. Very often: dyskinesias. Common: hallucinations, drowsiness, dizziness (including labyrinthine origin), orthostatic hypotension, hypotension, constipation, nausea, peripheral edema. In addition, in patients with Parkinson's disease treated with ropinirole in the form of of immediate release (up to 24 mg / day) the following side effects have been observed.monotherapy. Very often: fainting. Common: vomiting, heartburn, abdominal pain, swelling of the legs. Uncommon: psychotic reactions (other than hallucinations) including delirium, delusions, paranoia, sudden sleep bouts, excessive daytime sleepiness, orthostatic hypotension, hypotension (rarely severe). Not known: hypersensitivity reactions (including urticaria, angioneurotic edema, rash, pruritus), hepatic reactions (mainly increase in liver enzymes).Combination therapy. Very often: drowsiness, nausea. Common: confusion, heartburn. Uncommon: psychotic reactions (other than hallucinations) including delirium, delusions, paranoia, sudden sleep bouts, excessive daytime sleepiness, orthostatic hypotension, hypotension (rarely severe). Not known: hypersensitivity reactions (including urticaria, angioneurotic edema, rash, pruritus), hepatic reactions (mainly increase in liver enzymes). The use of ropinirole is associated with drowsiness and uncommonly with excessive daytime sleepiness and sudden sleep bouts. Patients treated with dopamine agonists, including ropinirole, may experience: pathological gambling, increased libido, pathological sexual activity, uncontrollable willingness to spend money and make purchases, gluttony and overeating.
Dosage:
Orally. Adults. Individual dose selection is recommended depending on the efficacy and tolerability of the drug. The starting dose is 2 mg once a day for 1 week of treatment; Starting from the second week, the dose should be increased to 4 mg once a day. The response to treatment may be seen with a 4 mg dose once a day. Patients who started treatment with a dose of 2 mg drug in the form of tablets. about once a day, if you experience side effects that you are not able to tolerate, you may benefit from switching to ropinirole in the form of tablets. with immediate release at a lower daily dose, divided into 3 equal doses. Treatment should be continued with the lowest dose in the form of tablets. about release allowing control of clinical symptoms. If the 4 mg dose once a day administered in the form of about release is not sufficient to achieve or maintain control of symptoms, then the daily dose may be increased by 2 mg at weekly or longer intervals up to a dose of 8 mg once a day. If this dose is not enough to achieve or maintain control of symptoms then the dose can be increased by 2-4 mg at 2-week intervals. or longer. The maximum daily dose of ropinirole in the form of sustained release is 24 mg. It is recommended to prescribe the smallest possible number of tablets to the patients, which is necessary to achieve the recommended dose, by using the highest available power of ropinirole in the form of tablets. about release. If the treatment is discontinued daily or longer, consider re-starting with a gradual increase in dose until the therapeutic dose is reached. Combined with levodopa may allow a gradual reduction in the dose of levodopa, depending on the clinical response. In clinical trials, the dose of levodopa was reduced by approximately 30%. In advanced Parkinson's disease in combination with levodopa, dyskinesias may occur during the initial titration increase, reducing the dose of levodopa may reduce dyskinesias. If treatment with another dopamine agonist is changed to ropinirole, the instructions of the MAH should be followed before discontinuation of the medicine. Change of treatment with ropinirole in the form of tablets of immediate release on the preparation in the form of about release can be done overnight. The dose of ropinirole in the form of about release is calculated on the basis of the total daily dose of ropinirole in the form ofabout the immediate release that the patient has taken so far. If the patient took 0.75-2.25 mg daily - the dose of the preparation about the 2 mg / day, 3-4 mg / day - 4 mg, 6 mg - 6 mg, 7.5-9 mg - 8 mg, 12 mg - 12 mg, dose of 15-18 mg - 16 mg, at a dose of 21 mg - 20 mg, at a dose of 24 mg - 24 mg. After switching to ropinirole treatment in the form of With prolonged release, the total daily dose may be adjusted depending on the clinical response to treatment. In patients over 65 years, the clearance of ropinirole is reduced by about 15% - the dose should be individually adjusted depending on the response to treatment; in patients aged 75 years and older, a slower increase in dose may be considered when starting treatment. No dose adjustment is required in patients with mild to moderate renal impairment (creatinine clearance 30-50 ml / min). In patients with end stage renal disease (undergoing hemodialysis) the following dose adjustments are required: initial dose - 2 mg once a day; further dose increases should be based on tolerability and efficacy; maximum dose of ropinirole - 18 mg / day in patients receiving regular hemodialysis. Supplementary doses after hemodialysis are not required. Use of the drug in patients with severe renal impairment (creatinine clearance less than 30 ml / min) without regular hemodialysis has not been studied. The tablets are taken once a day, at a similar time each day, regardless of the meal, swallowed whole, they must not be chewed, crushed or divided.