Sindranol tab. prolong p/o. 8 mg No. 28 Pharmathen International/Greece

Sindranol

Tablets should be taken once a day, at the same time, regardless of meals; swallow whole, without chewing or dividing into parts, because this may interfere with the release of the active substance from the dosage form. To achieve the required dose of ropinirole, patients are recommended to take the minimum number of extended-release tablets, using the maximum possible tablet dosages. In some patients, simultaneous use with fatty foods may increase AUC and/or Cmax by 2 times.

It is recommended to individually select the dose of the drug, taking into account effectiveness and tolerability. If the patient experiences drowsiness at any stage of dose selection, a dose reduction is recommended. If other adverse reactions develop, it is necessary to reduce the dose of the drug followed by a gradual increase in dose. The need for dose adjustment should be considered if one or more doses are missed.

Monotherapy

Initial dose selection

The recommended starting dose is 2 mg once daily for the first week; in the second week, the dose should be increased to 4 mg once daily. The therapeutic effect can be achieved with 4 mg once daily.

Treatment regimen

It is necessary to carry out therapy with ropinirole in the minimum effective dose.

Subsequently, if necessary, the dose is increased by 2 mg at intervals of at least 1 week to 8 mg per day.

If the therapeutic effect of the drug at a dose of 8 mg/day is not sufficiently pronounced or unstable, you can continue to increase the daily dose of the drug by 2-4 mg every 2 weeks or at longer intervals (until the required therapeutic effect is achieved). The maximum daily dose is 24 mg in one dose.

Combination therapy

With simultaneous use of the drug in doses used in monotherapy with levodopa, a gradual reduction in the dose of levodopa (up to 30%) is possible, depending on the clinical effect. In patients with advanced Parkinson's disease who are simultaneously receiving levodopa, dyskinesia may develop during dose adjustment of extended-release ropinirole. If dyskinesia occurs, the dose of levodopa should be reduced.

In case of switching from therapy with another dopamine receptor agonist to the drug, it is necessary to follow the recommendations regarding the withdrawal of the previously taken drug.

Cancellation of therapy

As with other dopamine receptor agonists, discontinuation of the drug should be carried out gradually, reducing the daily dose over at least 1 week.

Switching from ropinirole (immediate-release) tablet therapy to extended-release tablet therapy

Patients can be switched immediately from therapy with ropinirole immediate-release tablets to therapy with extended-release tablets.

The dose (extended-release tablets) should correspond to the daily dose of ropinirole immediate-release tablets taken. If necessary, the dose may be further adjusted depending on the therapeutic response.

Interruption of therapy

If you miss a dose (one or more) and then resume therapy, you must reselect the dose.

Special patient groups

Elderly patients: no dose adjustment is required. In patients aged 75 years and older, a slower dose adjustment is advisable.

Impaired renal function: in patients with mild or moderate renal impairment (creatinine clearance 30-50 ml/min), the clearance of ropinirole does not change. Therefore, no dose adjustment of ropinirole is required. The recommended starting dose of ropinirole in patients with end-stage renal failure on hemodialysis is 2 mg once daily. In the future, the dose is increased taking into account the tolerability and effectiveness of the drug. The maximum daily dose of ropinirole in patients on program (chronic) hemodialysis is 18 mg. Taking additional doses after hemodialysis is not required.

In patients with severe renal failure (creatinine clearance less than 30 ml/min) not receiving treatment with program (chronic) hemodialysis, the use of ropinirole has not been studied.

Sindranol 8 mg 28 pcs. extended-release film-coated tablets

pharmachologic effect

Ropinirole is an effective and highly selective non-ergoline agonist of dopamine D2-, D3-receptors, has peripheral and central effects.
The drug does not act on decaying presynaptic dopaminergic neurons of the substantia nigra and acts directly as a synthetic neurotransmitter. Thus, ropinirole reduces the degree of physical inactivity, rigidity and tremor, which are symptoms of Parkinson's disease.

Ropinirole compensates for dopamine deficiency in the substantia nigra and striatal systems by stimulating dopamine receptors in the striatum. Ropinirole acts at the level of the hypothalamus and pituitary gland, inhibiting the secretion of prolactin.

Ropinirole enhances the effects of levodopa, including control of the on/off phenomenon and the end-of-dose effect associated with long-term levodopa therapy.

The effect of ropinirole on myocardial repolarization.

The effect of ropinirole on the duration of the QT interval was studied in healthy volunteers (men and women) receiving ropinirole immediate-release tablets in doses of 0.5, 1.2 and 4 mg 1 time / day. The maximum prolongation of the QT interval when taking ropinirole at a dose of 1 mg was 3.46 ms compared with placebo. The upper limit of the one-sided 95% confidence interval (CI) for the maximum mean effect was less than 7.5 ms. The effect of ropinirole on the QT interval at higher doses has not been studied.

There is no risk of prolongation of the QT interval on the ECG when using ropinirole in doses up to 4 mg/day. It is impossible to completely eliminate the risk of prolongation of the QT interval on the ECG when using ropinirole, because there is no analysis of data on its use in doses up to 24 mg/day.

Composition and release form Sindranol 8 mg 28 pcs. extended-release film-coated tablets

Tablets - 1 tablet:

• Active ingredients: ropinirole 8 mg;
• Excipients: copolymer of methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate [2:0.1:1], hypromellose, sodium lauryl sulfate, copovidone, magnesium stearate;
• shell composition: opadry II pink 32K14834 (lactose monohydrate 40%, hypromellose-2910 (hypromellose-15cP) 28%, titanium dioxide 23.46%, triacetin 8%, red iron oxide dye 0.54%).

28 tablets per package.

Description of the dosage form

Long-acting tablets, film-coated, pink, round, biconvex; On a cross section, the core is almost white.

Directions for use and doses

It is recommended to individually select the dose of the drug, taking into account effectiveness and tolerability. If the patient experiences drowsiness at any stage of dose selection, it is recommended to reduce the dose of the drug. If other adverse reactions develop, it is necessary to reduce the dose of the drug followed by a gradual increase in dose.

The need to adjust the dose should be considered if the next dose (one or more) is missed.

Monotherapy.

Initial dose selection.

The recommended starting dose of Sindranol is 2 mg 1 time / day for the 1st week. In the 2nd week, the dose should be increased to 4 mg 1 time / day. The therapeutic effect can be achieved by using the drug Sindranol at a dose of 4 mg 1 time / day.

Treatment scheme.

It is necessary to carry out therapy with ropinirole in the minimum effective dose. Subsequently, if necessary, the dose is increased by 2 mg at intervals of at least 1 week to 8 mg/day.

If the therapeutic effect of the drug Sindranol at a dose of 8 mg/day is not sufficiently pronounced or is unstable, you can continue to increase the daily dose of the drug by 2-4 mg every 2 weeks or at longer intervals (until the required therapeutic effect is achieved).

The maximum daily dose is 24 mg in one dose.

Combination therapy.

With simultaneous use of the drug Sindranol in doses used in monotherapy with levodopa, a gradual reduction in the dose of levodopa (up to 30%) is possible, depending on the clinical effect. In patients with advanced Parkinson's disease who are simultaneously receiving levodopa, dyskinesia may develop during dose adjustment of extended-release ropinirole. If dyskinesia occurs, the dose of levodopa should be reduced.

In case of switching from therapy with another dopamine receptor agonist to the drug Sindranol, it is necessary to follow the recommendations regarding the withdrawal of the previously taken drug.

Cancellation of therapy.

As with other dopamine receptor agonists, Syndranol should be discontinued gradually, reducing the daily dose over at least 1 week.

Switching from ropinirole immediate-release tablet therapy to Syndranol extended-release tablet therapy.

Patients can be immediately switched from ropinirole immediate-release tablets to Syndranol extended-release tablets. The dose of ropinirole in Syndranol should correspond to the daily dose of ropinirole immediate-release tablets taken. The recommended appropriate doses of Sindranol (extended-release tablets) when switching from ropinirole therapy to immediate-release tablets are presented in the table below. When taking another dose of ropinirole immediate-release tablets not listed in the table, the patient should be switched to the nearest dose listed in the table:

If necessary, the dose may be further adjusted depending on the therapeutic response.

Interruption of therapy.

If you miss a dose (one or more) and then resume therapy, you must reselect the dose.

Special groups of patients.

In elderly patients, the clearance of ropinirole after oral administration is reduced by approximately 15% compared to younger patients. No dose adjustment is required in this category of patients. In patients aged 75 years and older, a slower dose titration is recommended.

In patients with mild or moderate renal impairment (creatinine clearance 30-50 ml/min), the clearance of ropinirole does not change. Therefore, no dose adjustment of ropinirole is required. The recommended starting dose of ropinirole in patients with end-stage renal failure on hemodialysis is 2 mg once a day. Subsequently, the dose is increased taking into account the tolerability and effectiveness of the drug. The maximum daily dose of ropinirole in patients on program (chronic) hemodialysis is 18 mg. Taking additional doses after hemodialysis is not required. In patients with severe renal failure (CR

Pharmacokinetics

Suction.

The bioavailability of ropinirole after oral administration is approximately 50% (36-57%). After oral administration of ropinirole extended-release tablets, its plasma concentration increases slowly. The average time to reach the maximum concentration of the drug in the blood plasma (Tmax) is 6-10 hours. At steady state, in patients with Parkinson's disease, after oral administration of 12 mg of ropinirole 1 time / day simultaneously with fatty foods, compared with administration on an empty stomach, an increase in systemic exposure to ropinirole. At the same time, there was an increase in AUC (90% CI [1.12; 1.28] and Cmax of the drug in blood plasma (90% CI [1.34; 1.56]) by an average of 20% and 44%, respectively, and Tmax was prolonged by 3 hours.

The systemic exposure of ropinirole when taking extended-release tablets corresponds to the systemic exposure when taking immediate-release tablets at the same daily dose.

High interindividual variability of pharmacokinetic parameters was noted. When using ropinirole in extended-release tablets at steady state, the interindividual variability in Cmax was 30-55%, AUC - 40-70%.

Distribution.

The connection with blood plasma proteins is low and amounts to 10-40%. Due to its high lipophilicity, ropinirole is characterized by a large Vd (about 7 l/kg).

Metabolism.

Ropinirole is actively metabolized in the liver mainly by the CYP1A2 isoenzyme. The main metabolite (N-depropyl) is inactive and is further converted to carbamyl glucuronide, carboxylic acid and N-depropyl hydroxy metabolites. Metabolites are predominantly excreted by the kidneys.

Excretion.

T1/2 of ropinirole from the systemic circulation averages about 6 hours. The increase in the duration of systemic action of ropinirole (AUC and Cmax) is approximately proportional to the increase in dose. There is no difference in the elimination of ropinirole after a single oral dose or with regular use.

Linearity/nonlinearity.

The pharmacokinetics of ropinirole at doses up to 24 mg/day are linear (ropinirole in the form of immediate-release tablets 8 mg 3 times/day).

Pharmacokinetics in certain groups of patients.

Pharmacokinetic parameters do not change in patients with Parkinson's disease with mild to moderate renal impairment. In patients with end-stage renal failure on program (chronic) hemodialysis, the clearance of ropinirole when taken orally is reduced by approximately 30%. The clearance of ropinirole metabolites is also reduced by approximately 60-80%. Therefore, the maximum daily dose in these cases is 18 mg.

Oral clearance of ropinirole is reduced by approximately 15% in patients aged 65 years and older compared with younger patients. No dose adjustment is required in this category of patients.

Indications for use Sindranol 8 mg 28 pcs. extended-release film-coated tablets

Parkinson's disease:

• As monotherapy in early stages of the disease in patients requiring dopaminergic therapy to delay the administration of levodopa;
• as part of combination therapy in patients receiving levodopa drugs, in order to increase the effectiveness of levodopa, including monitoring fluctuations in the therapeutic effect of levodopa (the “on-off” phenomenon) and the “end-of-dose” effect during chronic levodopa therapy, as well as in order to reduce the daily dose Levodopa.

Contraindications

• Severe renal failure (SC
• liver dysfunction;
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;
• hypersensitivity to ropinirole or any of the components included in the drug.

Ropinirole should be prescribed with caution to patients with severe cardiovascular diseases and severe cardiovascular insufficiency.

Ropinirole should only be prescribed to patients with a history of psychotic disorders if the expected benefit outweighs the potential risk.

Application of Sindranol 8 mg 28 pcs. extended-release film-coated tablets during pregnancy and lactation

Sindranol should not be used during breastfeeding, because the drug may inhibit lactation.

The use of the drug is contraindicated in patients under the age of 18 years.

special instructions

Given the risk of developing arterial hypotension in patients with severe cardiovascular insufficiency (in particular, coronary artery disease), it is recommended to monitor blood pressure, especially at the beginning of treatment. Concomitant use with antihypertensive and antiarrhythmic drugs has not been studied. Caution should be exercised when used simultaneously with these drugs, because the risk of developing hypotension, bradycardia or other arrhythmias is unknown.

Patients with or a history of psychotic disorders should be prescribed dopamine receptor agonists only in cases where the expected benefit outweighs the potential risk.

Patients should be warned about the possible development of drowsiness or episodes of sudden falling asleep, sometimes without previous drowsiness. If such reactions occur, discontinuation of ropinirole therapy should be considered.

Impaired impulse control (disorders of habits and impulses).

It is necessary to regularly monitor the possibility of developing impulse control disorders. Patients and their caregivers should be informed that when using dopamine receptor agonists, incl. ropinirole, it is possible to develop a syndrome of impulsive drives, including compulsive behavior, incl. pathological attraction to gambling, increased libido, hypersexuality, irresistible shopping urge, overeating. Desire disorders are usually reversible after reducing the dose or discontinuing the drug.

In some cases, when using ropinirole, other risk factors may include a history of compulsive behavior or the combined use of several dopaminergic drugs. In this case, the possibility of reducing the dose or discontinuing therapy should be considered.

Paradoxical worsening of restless legs syndrome has been observed with ropinirole therapy (earlier onset, increased severity of symptoms, or progression of symptoms to involve previously unaffected limbs) or rebound syndrome (relapse of symptoms) in the early morning hours (recurrence of symptoms in the early morning hours) . If these symptoms appear, it is necessary to reconsider the treatment tactics with ropinirole, adjust the dose, and possibly discontinue the drug.

The drug Sindranol is available in the form of prolonged-release film-coated tablets with the property of releasing the active substance within 24 hours. In the case of rapid passage of the drug through the gastrointestinal tract, there is a risk of incomplete release of the drug substance and the transfer of its residue into the stool.

Special information on excipients.

The drug contains lactose and is therefore contraindicated in patients with lactase deficiency, lactose intolerance, and glucose-galactose malabsorption syndrome.

Influence on the ability to drive vehicles and operate machinery.

Patients should be warned about possible adverse reactions during therapy with ropinirole. Patients should be informed that there are very rare cases of episodes of sudden falling asleep without any warning signs and cases of dizziness (even vertigo).

If the patient develops daytime sleepiness and/or has episodes of sudden falling asleep during the day that require active intervention, the patient should be warned that he should not drive a car, and he should also avoid other activities that require a high speed of psychomotor reactions.

Overdose

Symptoms: mainly associated with dopaminergic activity (nausea, vomiting, dizziness, drowsiness).

Treatment: administration of dopamine receptor antagonists, such as typical antipsychotics and metoclopramide.

Side effects Sindranol 8 mg 28 pcs. extended-release film-coated tablets

The adverse reactions presented below are listed according to organ system involvement and frequency of occurrence. The frequency of occurrence is determined as follows: very often (>=1/10); often (from >=1/100 to =1/1000 to =1/10,000 to

Clinical trial data.

Listed below are adverse reactions that occur at a higher frequency with ropinirole compared to placebo or at a higher or comparable frequency compared to the comparator drug.

Monotherapy.

Mental disorders: often - hallucinations.

From the nervous system: very often - drowsiness; often - dizziness (including vertigo).

From the cardiovascular system: infrequently - orthostatic hypotension, hypotension.

From the digestive system: very often - nausea; often - abdominal pain, dyspepsia, vomiting, constipation.

Other: often - peripheral edema (including edema of the lower extremities).

Simultaneous use with levodopa.

Mental disorders: often - hallucinations, confusion.

From the nervous system: very often - dyskinesia (in patients with a progressive form of Parkinson's disease taking ropinirole in combination with levodopa, during the titration of the dose of ropinirole, impaired coordination of movements may develop; according to clinical studies, reducing the dose of levodopa can lead to a decrease in the severity dyskinesia); often - drowsiness, dizziness (including vertigo).

From the cardiovascular system: often - orthostatic hypotension, hypotension.

From the digestive system: often - nausea, constipation.

Other: often - peripheral edema.

Data from post-registration observations.

Monotherapy.

From the immune system: very rarely - hypersensitivity reactions (including urticaria, angioedema, skin rash and itching).

Mental disorders: uncommon - psychotic reactions (excluding hallucinations), including delirium, delirium, paranoia; frequency unknown - impulsive drive syndrome, increased libido, including pathological gambling, hypersexuality, irresistible shopping urge, overeating, aggression*.

From the nervous system: very often - fainting; very rarely - severe drowsiness and episodes of sudden falling asleep**.

From the cardiovascular system: often - orthostatic hypotension, hypotension***.

From the digestive system: often - vomiting, heartburn, abdominal pain; frequency unknown - liver dysfunction (mainly increased activity of liver enzymes).

Other: often - swelling of the lower extremities.

Simultaneous use with levodopa.

From the immune system: very rarely - hypersensitivity reactions (including urticaria, angioedema, skin rash and itching).

Mental disorders: often - confusion; uncommon - psychotic reactions (excluding hallucinations), including delirium, delirium, paranoia; frequency unknown - impulsive drive syndrome, increased libido, including pathological gambling, hypersexuality, compulsive shopping, overeating, aggression*.

From the nervous system: very often - drowsiness; very rarely - severe drowsiness and episodes of sudden falling asleep**.

From the cardiovascular system: often - orthostatic hypotension, hypotension***.

From the digestive system: very often - nausea; often - heartburn; frequency unknown - liver dysfunction (mainly increased activity of liver enzymes).

* Aggression is associated with psychotic reactions and compulsive symptoms.

** As with other dopaminergic agents, severe somnolence and episodes of sudden sleep onset have been reported very rarely, primarily in patients with Parkinson's disease during post-marketing surveillance. There are cases of sudden falling asleep without any previous or obvious signs of drowsiness and fatigue. When the dose was reduced or the drug was discontinued, all symptoms disappeared. In most cases, concomitant sedatives were used).

*** As with other dopaminergic agents, hypotension, including orthostatic hypotension, has been observed during treatment with ropinirole.

Impaired impulse control (disorders of habits and impulses).

Pathological gambling, increased libido, hypersexuality, irresistible shopping urges, and compulsive overeating can occur in patients using dopamine receptor agonists, incl. Syndranol.

Drug interactions

There was no pharmacokinetic interaction observed between ropinirole and levodopa or domperidone, which would require dose adjustment of these drugs.

Antipsychotics and other centrally acting dopamine receptor antagonists, such as sulpiride or metoclopramide, may reduce the effectiveness of ropinirole, so concomitant use of these drugs should be avoided.

In patients receiving estrogens in high doses, an increase in the concentration of ropinirole in the blood plasma was noted. In women who were already receiving HRT before starting treatment with ropinirole, no dose adjustment of ropinirole is required. However, if HRT is prescribed or discontinued during treatment with ropinirole, a dose adjustment of Syndranol may be required.

Ropinirole is mainly metabolized by the CYP1A2 isoenzyme. With simultaneous use of ropinirole (at a dose of 2 mg 3 times / day) with ciprofloxacin, the Cmax and AUC of ropinirole increased by 60% and 84%, respectively, which can lead to the development of adverse events. In this regard, in patients receiving ropinirole, its dose should be adjusted when prescribing or discontinuing drugs that inhibit the CYP1A2 isoenzyme, such as ciprofloxacin, enoxacin or fluvoxamine.

In patients with Parkinson's disease taking concomitant digoxin, there was no interaction between digoxin and ropinirole that would require dose adjustment.

No pharmacokinetic interaction was observed between ropinirole (at a dose of 2 mg 3 times a day) and theophylline, which is a substrate of the CYP1A2 isoenzyme, in patients with Parkinson's disease.

There is no information about the possibility of interaction between ropinirole and ethanol. As with other centrally acting drugs, patients should be warned to avoid drinking alcohol during treatment with ropinirole.

Nicotine increases the activity of the CYP1A2 isoenzyme. If a patient stops or starts smoking during treatment with ropinirole, the dose may need to be adjusted.