Expiration date: 03/2026

The composition and form of issue:

Tablets prolonged action, film-coated. 1 tablet contains active substance:

ropinirole hydrochloride 2.28, 4,56 or 9,12 mg

(equivalent to 2 mg, 4 mg, 8 mg of ropinirole, respectively) 

excipients: hypromellose 2208 castor oil hydrogenated carmellose sodium povidone K29–32 maltodextrin magnesium stearate lactose monohydrate silica colloidal anhydrous mannitol, iron (III) oxide yellow E172 glyceryl dibehenate 

shell film (tablets 2 mg): pink dye Opadry OU-S-24900 (hypromellose 2910, titanium dioxide E171, macrogol 400, iron (II) oxide red E172, iron (III) oxide yellow E172) 

shell film (tablet 4 mg): light-brown dye Opadry OY-272Q7 (hypromellose 2910, titanium dioxide E171, macrogol 400, dye "sunset" yellow — E110, Indigo — E132) 

shell film (tablets 8 mg): red dye 03B25227 Opadry (hypromellose 2910, titanium dioxide E171, macrogol 400, iron (II) oxide red E172, iron (II) oxide black E172, iron (III) oxide yellow E172) 

Tablets 2 mg: blister of PVC/al or PTFE/al for 21 PCs the paper cartons 2 blister.

Tablets 2, 4 or 8 mg: blister of PVC/al or PTFE/al for 14 PCs. in cardboard pack of 2 or 6 blisters.

Description pharmaceutical form:

Tablets 2 mg: capsuleline biconvex shaped, film-coated pink, engraved with "GS" on one side and "3V2" on the other.

Tablets 4 mg: capsuleline biconvex shaped, film-coated light-brown color, with engraved "GS" on one side and "WXG" on the other.

Tablets 8 mg: capsuleline biconvex shaped, film-coated red, with engraved "GS" on one side and "5CC" on the other.

Pharmacokinetics:

The pharmacokinetics of ropinirole are similar in healthy people, patients with Parkinson's disease and patients with restless legs syndrome and varies depending on dosage forms.

Suction

The bioavailability of ropinirole after oral administration is low and is approximately 50% (36-57%). After oral administration of ropinirole tablets sustained release concentrations in plasma increased slowly, the average Tmax is 6 h At steady state in patients with Parkinson's disease after intake of 12 mg of ropinirole 1 time per day in combination with food rich in fats, the observed increase in systemic exposure of ropinirole, while there was an increase in AUC and Cmax by 20 and 44%, respectively, Tmax was lengthened to 3 h. However, in clinical studies of efficacy and safety of ropinirole taken regardless of meals.

The plasma protein binding and blood distribution

Linking blood plasma proteins is low (10-40%). Due to its high lipophilicity ropinirole is characterized by a large Vd (approximately 7 l/kg).

Metabolism

Ropinirole is mainly metabolised by the isoenzyme CYP1A2. Metabolite of ropinirole is mainly excreted by the kidneys.

Excretion

The average T1/2 of ropinirole from systemic blood flow is about 6 h. the increase in the duration of systemic action of ropinirole (Cmax and AUC) is approximately proportional to the dose increase. No differences in the excretion of ropinirole after single oral doses in or with regular use.

Special groups of patients

Patients of advanced age. The clearance of ropinirole after oral decreases by approximately 15% in elderly patients aged 65 years and older compared with younger patients. Dose adjustment in this category of patients is not required.

Patients with impaired renal function. The pharmacokinetic parameters are not changed in patients with impaired renal function mild to moderate and Parkinson's disease. In patients with end-stage renal disease under regular hemodialysis, the clearance of ropinirole when administered is reduced by about 30%.

Description pharmacological action:

Ropinirole is an effective and highly selective pergolino agonist of dopamine D2-, D3-receptor, which has peripheral and Central effects.

The drug has no effect on the collapsing of the presynaptic dopaminergic neurons of the black substance and acts directly as a synthetic neurotransmitter. Ropinirole reduces the degree of inactivity, rigidity and tremor, which are symptoms of Parkinson's disease.

Ropinirole make up for the deficiency of dopamine in the system matter and black striped body by stimulating dopamine receptors in the striatum.

Ropinirole enhances the effects of levodopa, including control of the frequency of the phenomenon of on/off and the effect of late doses associated with prolonged administration of levodopa, and allows to reduce the daily dose of levodopa.

Ropinirole has an effect on the level of the hypothalamus and pituitary, inhibiting the secretion of prolactin.

Indications:

Parkinson's Disease:

• monotherapy in the early stages of the disease patients requiring dopaminergic therapy to delay the appointment of levodopa
  
• in combination therapy in patients receiving levodopa, to enhance the effectiveness of levodopa, including control of the oscillation (on/off) and the effect of late doses on the background of chronic therapy with levodopa and to reduce the daily dose of levodopa.
  

Contraindications:

• hypersensitivity to ropinirole or any component of the drug
  
• pregnancy and lactation
  
• the liver
  
• severe violations of kidney function (Cl creatinine <30 ml/min), in which there is no regular hemodialysis
  
• rare hereditary diseases: lactose intolerance, lactase deficiency, malabsorption of glucose or galactose
  
• children up to age 18 years
  
• acute psychosis.
  

With caution. In connection with the pharmacological action of ropinirole should be administered with caution to patients with severe heart failure. Ropinirole can be given to patients with a psychotic disorder in history only if the expected benefit from its use outweighs the potential risk.

Side effects:

Adverse reactions are described below by organ system and frequency. Criteria frequency of adverse reactions: very often (&ge1/10) frequently (&GE. 1/100, <1/10), sometimes (&ge1/1000, <1/100) rare (&ge1/10000, <1/1000) very rare (<1/10000), including isolated cases.

Data from clinical studies in patients with Parkinson's disease

Frequency	Use as monotherapy	The use in combination therapy
Psychics
Often	Hallucinations	Hallucinations, confusion
From the nervous system
Very often	Drowsiness	Dyskinesia1
Often	Dizziness (up to strong)	Drowsiness, dizziness (up to strong)
From the CCC
Often		Orthostatic hypotension, decrease in blood pressure
Sometimes	Orthostatic hypotension, decrease in blood pressure
Gastrointestinal tract
Very often	Nausea
Often	Abdominal pain, dyspepsia, vomiting, constipation	Nausea, constipation
General and local reactions
Often	Peripheral edema (including swelling of the feet)	Peripheral edema

1U in patients with progressive form of the disease, the host Requip, Modutab in combination with levodopa, during titration of doses may develop disorders of coordination of movements. It has been shown that the abolition of levodopa may reduce this symptoms.

Post-marketing data

The immune system: very rarely — hypersensitivity reactions, including urticaria, angioedema, rash, and itching.

Psychics: sometimes — psychotic state including delirium and delirium disorders of perception, including illusion (excluding hallucinations) increased impulsiveness, increased libido, including hypersexuality, pathological attraction to gambling.

From the nervous system: very rarely — severe drowsiness, sudden sleep episodes (as in the case of other dopaminergic funds, these symptoms are very rarely observed in patients with Parkinson's disease at lower doses or discontinuation of therapy all symptoms disappeared in most cases the use of concomitant sedatives).

From the CCC: often — orthostatic hypotension, decrease in blood pressure.

Drug interactions:

Typical antipsychotics and other dopamine antagonists Central action, such as sulpiride or metoclopramide, may diminish the effectiveness of ropinirole and, therefore, avoid the simultaneous appointment of these drugs with ropinirole.

Not marked pharmacokinetic interaction between ropinirole and levodopa or domperidone which would require correction doses of these drugs.

Ropinirole does not interact with other drugs commonly used for the treatment of Parkinson's disease.

In patients with Parkinson's disease who were taking digoxin at the same time, there were no interactions of this drug with the ropinirole, which would require correction doses.

Ropinirole is mainly metabolised by the isoenzyme CYP1A2 enzyme of the cytochrome P450. Pharmacokinetic studies in patients with Parkinson's disease revealed that ciprofloxacin increases the Cmax and AUC of ropinirole by approximately 60 and 84%, respectively. In this regard, in patients receiving ropinirole, its dose must be adjusted in the appointment and withdrawal of drugs that inhibit the isoenzyme CYP1A2, e.g. ciprofloxacin, fluvoxamine or enoxacin.

Pharmacokinetic drug interaction study in patients with Parkinson's disease between ropinirole and theophylline is a substrate of the isoenzyme CYP1A2, showed that the pharmacokinetics of drugs is not changed. In connection with simultaneous application of ropinirole with other substrates of CYP1A2 isoenzyme, the pharmacokinetics of ropinirole is not affected.

Increasing the concentration of ropinirole in plasma was observed in patients treated with estrogens at high doses. Patients receiving hormone replacement therapy before starting treatment with ropinirole, the treatment of these drugs can be started in the usual way. However, in the event of termination of hormone replacement therapy or the beginning of it during treatment with ropinirole you may need dose correction.

Information on the possibilities for interaction between ropinirole and alcohol. As in the case with other centrally acting drugs, patients should be warned of the need to refrain from drinking alcohol during treatment with ropinirole.

It is known that nicotine induces CYP1A2 isoenzyme, so if a patient starts or stops Smoking during treatment with ropinirole, you may need dose correction.

Method of application and dose:

Inside.

Requip, Modutab should be taken 1 time a day at the same time regardless of the meal. Take tablets whole without chewing, without breaking.

The need for titration of dose should be considered when skipping the dose (one or more).

It is recommended to reduce the dose if the patient experiences drowsiness at any stage of the titration.

With the development of other adverse reactions is necessary to reduce the dose of the drug with subsequent gradual increase of the dose.

It is recommended that individual dose in accordance with the effectiveness and tolerability of the drug.

Monotherapy

The beginning of the treatment. The recommended starting dose Requip, Modutab is 2 mg 1 times a day for 1 week. Subsequently, increase the dose to 2 mg at intervals of no less than 1 week up to 8 mg/day.

Interval with increasing doses, weeks	1	2	3	4
Daily dose, mg	2	4	6	8

The maintenance dose. If after dose selection, the therapeutic effect is not expressed or is unstable, you can continue increasing the daily dose to 4 mg at intervals of 1-2 weeks (to achieve the desired therapeutic effect). The dose may be changed depending on therapeutic effect and increased to a maximum dose of 24 mg 1 time per day.

Combination therapy

When using the drug Requip, Modutab in the doses used in monotherapy, in combination with levodopa, the levodopa dose can be gradually reduced (depending on clinical effect). In clinical studies in patients receiving both Requip, Modutab tablets with delayed release, levodopa dose was reduced gradually by approximately 30%. In patients with progressive form of the disease, the host Requip, Modutab in combination with levodopa, during the titration of the dose of ropinirole may experience dyskinesia. Dose reduction of levodopa may reduce this symptoms.

Cancel therapy

As with other dofaminergicheskie drugs, Requip, Modutab should be abolished, gradually reducing the daily dose for at least 1 week.

If treatment was interrupted for 1 day or longer, with the resumption of therapy should consider the need for dose titration.

Special groups of patients

Elderly patients. Despite the possible decrease in clearance of the drug in patients aged 65 years and older, titration of the dose of ropinirole in this category of patients was carried out as usual.

Patients with renal impairment mild and moderate severity. In patients with impaired renal function mild and moderate severity (creatinine Cl 30-50 ml/min) clearance of ropinirole is not changed, dose adjustment of ropinirole is not required.

Patients with end-stage renal disease on hemodialysis. Recommended in the initial dose of ropinirole is 2 mg 1 times per day. Subsequent increase in doses should be based on an assessment of the tolerability and effectiveness. The maximum daily dose in patients on regular hemodialysis is 18 mg. the Introduction of maintenance doses after hemodialysis not necessary.

Overdose:

Symptoms: nausea, vomiting, dizziness, drowsiness (related to dopaminergic action of ropinirole).

Treatment: these symptoms can be corrected with the appropriate treatment with dopamine antagonists such as typical neuroleptics and metoclopramide.

Precautions:

Patients should be warned about the possible development of drowsiness or sudden sleep episodes, sometimes not pragarauskas drowsiness. In the event of such reactions should consider discontinuation of therapy.

It is recommended that monitoring of blood pressure because of the possibility of orthostatic hypotension.

In patients receiving dopaminergic drugs, including ropinirole, reported disorders of desire, including compulsive behaviors such as pathological attraction to gambling and hypersexuality. According to the literature these adverse effects of therapy were observed in patients with Parkinson's disease, receiving high doses of dopaminergic drugs other risk factors may be compulsive behavior in the history of, or a combination of several dopaminergic drugs. In this case, you should consider dose reduction or discontinuation of therapy.

Paradoxical deterioration during restless legs syndrome was noted during therapy with ropinirole (earlier initiation, increased intensity of manifestations or progression of symptoms with seizure previously unaffected limbs), or the syndrome of a ricochet in the early morning hours (relapse of symptoms in the early morning hours). If you encounter these symptoms it is necessary to reconsider the tactics of treatment with ropinirole, to clarify the dosage up to a possible withdrawal of the drug.

Effects on ability to drive or to perform work requiring high speed physical and mental reactions. Patients should be warned about possible adverse reactions during treatment with ropinirole.

Patients should be informed that there are very rare cases of sudden episodes of falling asleep without any warning or obvious signs of daytime sleepiness and cases of dizziness, sometimes expressed. With the development of daytime sleepiness or episodes of falling asleep during the day, requiring active intervention, the patient should be warned that he should not drive and should avoid other activities requiring high speed of psychomotor reactions and attention.