Sindranol, 2 mg 28 pcs

Parkinson’s disease:

– Monotherapy for early stages of the disease in patients requiring dopaminergic therapy to delay prescription of levodopa drugs.

– As combination therapy in patients receiving levodopa drugs to improve levodopa efficacy, including control of fluctuations in levodopa therapeutic effects (on-off phenomenon) and “end-of-dose” effects on chronic levodopa therapy, and to reduce daily levodopa dosing.

Active ingredient

Composition

Long-acting, film-coated tablets, 2 mg.

On 1 tablet:

Active substance:

Ropinirole hydrochloride 2.28 mg, which corresponds to ropinirole 2 mg.

Auxiliary substances:

Methyl methacrylate,

Trimethylammonioethyl methacrylate chloride and ethyl acrylate copolymer [2:0.1:1] 5.28 mg;

hypromellose 89.955 mg;

sodium lauryl sulfate 6.75 mg;

copovidone 44.64 mg;

magnesium stearate 1.095 mg.

Covering:

Opadray II pink 32K14834 (4.5 mg)/ opadray yellowish brown OY-27207 (9 mg)/ opadray red 03B25227 (18 mg).

Opadray II pink 32K14834:

Lactose monohydrate 40% (1.8 mg); hypromellose-2910 (hypromellose-15cP) 28% (1.26 mg); titanium dioxide 23.46% (1.0557 mg); triacetin 8% (0.36 mg); iron oxide red dye 0.54% (0.0243 mg).

Opadray yellowish brown OY-27207:

Hypromellose-2910 (hypromellose-6cP) 62.5% (5.625 mg); 21.25% titanium dioxide (1.9125 mg); sunset yellow dye, aluminum varnish (FD&C Yellow #6) (E110) 9% (0.81 mg); macrogol-400 6.25% (0.5625 mg); indigo carmine, aluminum varnish (FD&C blue #2) (E132) 1% (0.09 mg).

Opadray red 03B25227:

Hypromellose-2910 (hypromellose-bsP) 62.5% (11.25 mg); titanium dioxide 24.19% (4.3542 mg); macrogol-400 6.25% (1.125 mg); Red iron oxide 6.14% (1.105 mg); Black iron oxide 0.89% (0.1602 mg); Yellow iron oxide 0.03% (0.0054 mg).

How to take, the dosage

To be taken orally. Sindranol® should be taken once a day at the same time regardless of meals. Patients are recommended to take the minimum number of sustained release tablets to achieve the required dose of ropinirole using the maximum possible doses of the drug tablets. In some patients, concomitant use with fatty foods may increase AUC and/or Cmax by 2 times.

The tablets Sindranol® should be swallowed whole. It should not be chewed or divided into portions because the coating of the tablet provides prolonged release of ropinirole.

Individual adjustment of the dose of the drug is recommended based on efficacy 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, the dose of the drug should be reduced, followed by a gradual increase in the dose.

The need for dose adjustment should be considered if a dose (one or more) is missed.

Monotherapy

The initial dose selection

The recommended starting dose of Sindranol® is 2 mg once daily for the first week. In the second week, the dose should be increased to 4 mg once daily. Therapeutic effect can be achieved with the use of Sindranol® in a dose of 4 mg once daily.

The treatment regimen

The therapy with ropinirole should be given in the lowest 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 8 mg daily dose of Sindranol® is not sufficiently pronounced or is unstable, the daily dose of the drug may be increased by 2-4 mg every two weeks or at longer intervals (until the desired therapeutic effect is achieved). The maximum daily dose is 24 mg at one time.

Combination therapy

In concomitant use of Sindranol® in doses used for 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 receiving levodopa concomitantly, dyskinesia may develop while adjusting the dose of sustained-release ropinirole. If dyskinesia occurs, the dose of levodopa should be reduced.

If therapy is switched from another dopamine receptor agonist to Sindranol®, recommendations regarding withdrawal of the previous medication should be followed.

Cancellation of therapy

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

Interruption of therapy

If a dose is missed (one or more) and therapy is resumed, the dose should be readjusted.

Special patient groups

Patients in the elderly

The clearance of ropinirole after oral administration is reduced by about 15% in elderly patients compared to younger patients. No dose adjustment is required in this category of patients.

In patients aged 75 years and older, a slower dose adjustment is appropriate.

Patients with mild to moderate renal impairment (CKD 30-50 ml/min) do not have an altered clearance of ropinirole. 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. The dose is subsequently increased according to the tolerability and efficacy of the drug. Maximum daily dose of ropinirole in patients on programmed (chronic) hemodialysis is 18 mg. No additional doses are required after hemodialysis.

The use of ropinirole has not been studied in patients with severe renal impairment (CK<30 ml/min) not on programmed (chronic) hemodialysis.

Interaction

No pharmacokinetic interaction has been noted between ropinirole and levodopa or domperidone that would require dose adjustments of these drugs.

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

In patients receiving high doses of estrogens, an increase in plasma concentrations of ropinirole has been noted. In women who were already receiving hormone replacement therapy (HRT) prior to treatment with ropinirole, no correction of ropinirole dose is required. However, in case of prescription of HRT or its cancellation during treatment with ropinirole, correction of the dose of Sindranol® may be required.

Ropinirole is mainly metabolized by the CYP1A2 isoenzyme. Co-administration of ropinirole (2 mg three times daily) with ciprofloxacin increased cmax and AUC of ropinirole by 60% and 84% respectively, which may lead to the development of side effects. Therefore, in patients receiving ropinirole its dose should be adjusted when prescribing or cancelling drugs that inhibit CYP1A2 isoenzyme, such as ciprofloxacin, enoxacin or fluvoxamine.

In patients with Parkinson’s disease taking digoxin concomitantly, no interaction between digoxin and ropinirole has been identified that would require dose adjustments. No pharmacokinetic interaction was noted between ropinirole (at a dose of 2 mg three times daily) and theophylline, which is a substrate of CYP1A2 isoenzyme, in patients with Parkinson’s disease.

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

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

Special Instructions

With regard to the risk of arterial hypotension in patients with severe cardiovascular insufficiency (in particular, with coronary heart disease), it is recommended to monitor BP, especially at the beginning of treatment. Concomitant use with hypotensive and antiarrhythmic drugs has not been studied. Caution should be exercised when concomitant use with the indicated drugs, since the risk of arterial hypotension, bradycardia or other arrhythmias is unknown.

Patients with psychotic disorders or a history of psychotic disorders should only be prescribed dopamine receptor agonists if the expected benefit of use exceeds the potential risk.

Patients should be warned about the possible development of somnolence or episodes of sudden falling asleep, sometimes without preceding somnolence. If these reactions occur, discontinuation of therapy with ropinirole should be considered.

Impulse control disorders (habit and craving disorders)

The possibility of developing impulse control disorders should be monitored regularly. Patients and their caregivers should be informed that the use of dopamine receptor agonists, including ropinirole, may result in the development of impulsive cravings, including compulsive behavior, including pathological gambling cravings, increased libido, hypersexuality, compulsive shopping cravings, and overeating. Cravings disorders are usually reversible after a reduction in dose or discontinuation of 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. Dose reduction or withdrawal of therapy should be considered in this case.

Paradoxical worsening of restless legs syndrome has been noted with therapy with ropinirole (earlier onset, increased intensity of manifestations, or progression of symptoms with seizure of previously unaffected limbs), or ricochet syndrome (recurrence of symptoms) in the early morning hours (recurrence of symptoms in the early morning hours). If these symptoms occur, ropinirole treatment should be reconsidered, and the dosage should be adjusted up to and including possible withdrawal of the drug.

The drug Sindranol® is available as sustained release film-coated tablets with the ability to release the active substance within 24 hours. In case of rapid passage of the drug through the gastrointestinal tract there is a risk of incomplete release of the drug and transfer of the drug residue into the stool.

Special information about excipients

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

The effect on the ability to drive:

Patients should be advised of possible adverse reactions during therapy with ropinirole. Patients should be informed that there are very rare cases of the development of episodes of sudden falling asleep without any precursor and cases of dizziness (up to vertigo).

If a patient develops drowsiness during the day and/or has episodes of sudden falling asleep during the day that require active intervention, the patient should be warned not to drive and should avoid other activities that require high psychomotor reaction rates.

Contraindications

– Hypersensitivity to ropinirole or any of the ingredients of the drug;

– Severe renal failure (creatinine clearance (CK) < 30 ml/min) in patients not treated with program (chronic) hemodialysis;

– liver dysfunction;

– age less than 18 years;

– period of breastfeeding;

– lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

With caution:

Ropinirol is used with caution in patients with severe cardiovascular disease and severe cardiovascular insufficiency.

Ropinirol should only be prescribed to patients with a history of psychotic disorders if the expected benefits of its use exceed the potential risks.

Side effects

The adverse reactions presented below are listed according to organ system involvement and frequency of occurrence. The frequency is defined as follows: very common: ≥1/10; common: ≥1/100 to < 1/10; infrequent: ≥1/1000 to < 1/100; rare: ≥1/10 000 to < 1/1000; very rare: < 1/10 000; frequency unknown: cannot be estimated based on available data.

Within each group, the frequency of adverse reactions is presented in decreasing order of significance.

Overdose

Symptoms: mainly related to dopaminergic activity (nausea, vomiting, dizziness, drowsiness).

Treatment: prescription of dopamine receptor antagonists such as typical neuroleptics and metoclopramide.

Similarities