Rolprin CP - instructions for use, dose, side effects, contraindications

Active substanceRopiniroleRopinirole

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Dosage form: & nbsp

tablets of prolonged action, film-coated

Composition:

1 tablet 2 mg contains:

Active substance:

Ropinirole hydrochloride 2.28 mg (equivalent to ropinirole 2,00 mg)

Excipients: hypromellose 250.00 mg, lactose monohydrate 164.72 mg, silicon colloidal dioxide 3.00 mg, carbomer 20.00 mg, castor oil hydrogenated 50.00 mg, magnesium stearate 10.00 mg

Film sheath:

* Drop off white Y-1-7000 14.925 mg, iron dye red oxide (E172) 0.045 mg, iron dye oxide yellow (E172) 0.030 mg

* Drop off white Y-1-7000: hypromellose - 62.50%, titanium dioxide - 31.25%, macrogol-400 - 6.25%.

1 tablet of 4 mg contains:

Active substance:

Ropinirole hydrochloride 4.56 mg (equivalent to ropinirole 4.00 mg)

Excipients: hypromellose 250.00 mg, lactose monohydrate 162.44 mg, silicon colloidal dioxide 3.00 mg, carbomer 20.00 mg, castor oil hydrogenated 50.00 mg, magnesium stearate 10.00 mg

Film sheath:

* Drop off white Y-1-7000 14.300 mg, iron dye red oxide (E172) 0.140 mg, iron dye oxide yellow (E172) 0.490 mg, ferric iron oxide black (E172) 0.070 mg

* Drop off white Y-1-7000: hypromellose - 62.50%, titanium dioxide - 31.25%, macrogol-400 - 6.25%.

1 tablet of 8 mg contains:

Active substance:

Ropinirole hydrochloride 9.12 mg (equivalent to ropinirole 8.00 mg)

Excipients: hypromellose 250.00 mg, lactose monohydrate 157.88 mg, silicon dioxide colloid 3.00 mg, carbomer 20.00 mg, castor oil hydrogenated 50.00 mg, magnesium stearate 10.00 mg

Film sheath:

* Drop off white Y-1-7000 14,300 mg, ferric iron oxide red (E172) 0.490 mg, ferric iron oxide yellow (E172) 0.140 mg, ferric oxide black oxide (E172) 0.070 mg

* Drop off white Y-1-7000: hypromellose - 62.50%, titanium dioxide - 31.25%, macrogol-400 - 6.25%.

Description:

Tablets 2 mg:

Oval biconvex tablets covered with a pink film cover.

Tablets 4 mg:

Oval biconvex tablets covered with a film coating of light brown color.

Tablets 8 mg:

Oval biconvex tablets covered with a film coat of a brownish pink color.

Pharmacotherapeutic group:An antiparkinsonian agent, a dopamine agonist.

ATX: & nbsp

N.04.B.C Stimulants of dopamine receptors

N.04.B.C.04 Ropinirole

Pharmacodynamics:

Ropinirole is an effective and highly selective nonergonomine agonist

D₂-, D₃dopamine receptors, which has a peripheral and central action.

The drug does not affect the collapsing presynaptic dopaminergic neurons of black matter and acts directly as a synthetic neurotransmitter. In this way, ropinirole reduces the degree of hypodynamia, rigidity and tremor, which are symptoms of Parkinson's disease.

Ropinirole compensates for dopamine deficiency in systems of black matter and the striatum by stimulating dopamine receptors in the striatum. Ropinirole has an effect at the hypothalamic and pituitary levels, inhibiting the secretion of prolactin.

Ropinirole enhances the effects of levodopa, including monitoring the incidence 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 interval QT were studied in healthy volunteers (men and women) who received ropinirole in immediate-release tablets at doses of 0.5, 1.2 and 4 mg once daily. The maximum elongation of the interval QT when taking ropinirole at a dose of 1 mg was 3.46 ms compared with placebo.The upper limit of the unilateral 95% confidence interval for the maximum average effect was less than 7.5 ms. The effect of ropinirole on the duration of the interval QT when it was taken in higher doses was not studied. There is no risk of lengthening the interval QT on the ECG with the use of ropinirole in doses up to 4 mg / day. Completely eliminate the risk of lengthening the interval QT on the ECG with the use of ropinirole is impossible, since there is no analysis of the data on its use in doses up to 24 mg / day.

Pharmacokinetics:

Suction

The bioavailability of ropinirole after ingestion is approximately 50% (36-57%). After ingestion of ropinirole in long-acting tablets, its concentration in the blood plasma increases slowly, the mean time to reach the maximum concentration (TC_m_Oh) in the blood plasma is 6-10 hours. In an equilibrium state in patients with Parkinson's disease after ingestion of 12 mg of ropinirole once daily with fatty foods, compared with the use of an empty stomach, an increase in the system exposure of ropinirole was observed. At the same time, an increase in the area under the concentration-time curve was noted (AUC) (90% confidence interval [1.12, 1.28]) and maximum concentration (C_m_Oh) (90% confidence interval [1.34, 1.56]) in the blood plasma, on average, by 20% and 44%, respectively, and TC_m_Ohextended for 3 hours.

The system exposure of ropinirole with the use of long-acting tablets corresponds to systemic exposure when taking immediate-release tablets at the same daily dose. The pharmacokinetics of ropinirole at a dose of up to 24 mg / day is linear (immediate-release ropinirole tablets 8 mg 3 times a day).

Distribution

Communication with plasma proteins is low and is 10-40 %. Due to high lipophilicity ropinirole characterized by a large volume of distribution (about 7 l / kg).

Metabolism

Ropinirole is actively metabolized in the liver mainly by isoenzyme CYP1A2. The main metabolite (N-dropropil metabolite) is inactive and subsequently converted to carbamylglucuronide, carboxylic acid and N-Dropropyl hydroxymetabolites. Metabolites are mainly excreted by the kidneys.

Excretion

The half-life of ropinirole from the systemic blood stream, on average, is about 6 hours. The increase in the duration of systemic action of ropinirole (C_m_Oh and AUC) approximately in proportion to the increase in dose.There is no difference in the excretion of ropinirole after a single dose inward or with its regular application. High intraindividual variability of pharmacokinetics indices was noted. When ropinirole is used in tablets of prolonged action in the equilibrium state, the interindividual variability of C_m_Oh was 30-55%, AUC - 40-70 %.

Pharmacokinetics in selected patient groups

Impaired renal function

Pharmacokinetic parameters do not change in patients with Parkinson's disease with mild and moderate renal dysfunction.

In patients with terminal renal failure who are on programmed (chronic) hemodialysis, the clearance of ropinirole during ingestion is reduced by approximately 30%. The clearance of the metabolites of ropinirole is also reduced by approximately 60-80%. Therefore, the maximum daily dose in these cases is 18 mg.

Elderly patients

The clearance of ropinirole after ingestion is reduced by approximately 15% in patients 65 years of age or older compared with younger patients. Dose adjustments are not required for this category of patients.

Indications:

Parkinson's disease:

- monotherapy of early stages of the disease in patients requiring dopaminergic therapy;

- as a combination therapy in patients receiving levodopa preparations in order to increase the effectiveness of levodopa, including the control of fluctuations in the therapeutic action of levodopa (the phenomenon of "on-off") and the effect of "end-of-dose" on the background of chronic levodopa therapy, as well as to reduce daily dose of levodopa.

Contraindications:

- Hypersensitivity to the active ingredient or any of the components of the drug.

- Renal failure of severe degree (creatinine clearance (CK) less than 30 ml / min) in patients not receiving treatment with chronic hemodialysis.

- Violation of the function of the liver.

- Children under 18 years.

- Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome.

- Breastfeeding period.

Carefully:In connection with the pharmacological action of ropinirole, it should be administered with caution to patients with severe cardiovascular insufficiency. Ropinirole can be prescribed to patients with psychotic disorders in history, in cases where the expected benefit of its use exceeds the potential risk.

Pregnancy and lactation:There is insufficient data on the use of ropinirole in pregnant women. In animal studies, reproductive toxicity has been identified. The potential risk of use in pregnant women is unknown, so the use of Rolprin® CP during pregnancy is possible if the potential benefit to the mother exceeds the risk to the fetus. It should not be taken during breastfeeding, because it can inhibit lactation.

Dosing and Administration:

Inside. The preparation of Rolprin® CP should be taken once a day, at the same time, regardless of food intake. In order to achieve the required dose of ropinirole, it is recommended that patients take the minimum number of prolonged-release tablets using the maximum possible dosages of the tablets of the Rolprin® SR preparation. In some patients, simultaneous use with fatty foods can increase AUC and / or Cmax by a factor of 2. ROLRIN® CP tablets should be swallowed whole. Do not chew or divide into parts, since the tablet shell provides a prolonged release of ropinirole. It is recommended to select the individual dose of the drug taking into account the effectiveness and tolerability.If the patient experiences drowsiness at any stage of dose selection, it is recommended to reduce the dose of the drug. When developing other unwanted reactions, it is necessary to reduce the dose of the drug followed by a gradual increase in the dose. The need for dose selection should be considered when skipping a dose (one or more).

Monotherapy

Initial dose selection

The recommended starting dose of Rolprin® CP is 2 mg once a day during the first week, in the second week the dose should be increased to 4 mg once a day. The therapeutic effect can be achieved with the use of Rolprin® CP in a dose of 4 mg once a day.

Treatment Scheme

It is necessary to conduct therapy with ropinirole in the minimum effective dose. In the future, if necessary, increase the dose by 2 mg at intervals of at least 1 week to 8 mg per day. If the therapeutic effect of Rolprin® CP at a dose of 8 mg / day is not sufficiently expressed or is unstable, it is possible to continue increasing the daily dose of the drug by 2-4 mg every 2 weeks or with longer intervals (until the necessary therapeutic effect is achieved).The maximum daily dose is 24 mg in one session.

Combination Therapy

With the simultaneous use of Rolprin® CP in doses used in monotherapy with levodopa, a gradual decrease in the dose of levodopa (up to 30%), depending on the clinical effect, is possible. In patients with a progressive form of Parkinson's disease concomitantly receiving levodopa, dyskinesia may develop during the period of selecting a dose of ropinirole for prolonged release. When dyskinesia occurs, the dose of levodopa should be reduced.

In the case of switching from therapy with another dopamine receptor agonist to the Rolprin® preparation CP it is necessary to follow the recommendations regarding the cancellation of the previously taken drug.

Abolition of therapy

As with other dopamine receptor agonists, Rolprin® CP should be abolished gradually, reducing the daily dose for at least 1 week.

Transition from the therapy with ropinirole tablets (immediate-release) to long-acting Rolprine® CP

Patients can be immediately transferred from the therapy with ropinirole tablets with the immediate release of long-acting Rolprin® SR for tablets.

The dose of Rolprin® CP (sustained-release tablets) should correspond to the daily intake of ropinirole in immediate-release tablets. Recommended appropriate doses of Rolprin® CP (prolonged-release tablets) in the case of transition from immediate-release ropinirole tablets are shown in the table below (see below). When taking another dose of immediate release ropinirole tablets, not specified in the table, the patient should be transferred to the nearest dose indicated in the table:

Ropinirole, instant tablets liberation Daily dose (mg)	Ropinirole, prolonged-release tablets (Rolprin® preparation CP) Daily dose (mg)
0,75 - 2,25	2
3-4,5	4
6	6
7,5-9	8
12	12
15-18	16
21	20
24	24

If necessary, in the future the dose can be adjusted depending on the therapeutic response (see subsections "Initial dose selection" and "Treatment schedule").

Interruption of therapy

If you miss a dose (one or more) and continue to resume therapy, you need to re-adjust the dose.

Special patient groups

Elderly patients

The clearance of ropinirole after ingestion is reduced by approximately 15% in elderly patients compared with younger patients. Dose adjustments are not required for this category of patients.

In patients aged 75 years and older, a slower dose selection is advisable.

Impaired renal function

In patients with mild or moderate renal dysfunction (CK 30-50 ml / min), the clearance of ropinirole does not change. Therefore, correction of the dose of ropinirole is not 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 programmed (chronic) hemodialysis is 18 mg. Admission of additional doses after hemodialysis is not required.

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

Side effects:

Frequency classification development of side effects of the World Organization Health (WHO):

Often >1/10

often from > 1/100 to <1/10

infrequently from> 1/1000 to <1/100

rarely from > 1/10000 to <1/1000

rarely < 1/10000

the frequency of the unknown can not be estimated from the available data.

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

Undesirable reactions observed in patients with Parkinson's disease in clinical studies on the use of ropinirole in prolonged-release tablets at doses up to 24 mg / day

	Monotherapy	Simultaneous use with levodopa
Disorders of the psyche:
often	hallucinations	hallucinations
Impaired nervous system:
Often	drowsiness	dyskinesia *
often	dizziness (including vertigo)	drowsiness, dizziness (including vertigo)
Vascular disorders:
often		orthostatic hypotension, lowering of blood pressure (BP)
infrequently	Orthostatic hypotension, lower blood pressure
Disorders from the gastrointestinal tract:
Often	nausea
often	constipation	nausea, constipation
General disorders and disorders at the site of administration:
often	peripheral edema	peripheral edema

* Patients with a progressive form of Parkinson's disease during the period of choosing a dose of ropinirole can develop dyskinesia. According to clinical studies, a decrease in the dose of levodopa may lead to a decrease in the severity of dyskinesia.

Undesirable reactions,observed in patients with Parkinson's disease in clinical trials (at doses up to 24 mg / day), and / or post-marketing application of immediate-release ropinirole

	Monotherapy	Simultaneous use with levodopa
Immune system disorders:
frequency unknown	reactions Hypersensitivity (including hives, angioedema, skin rash and itchy skin)	reactions Hypersensitivity (including hives, angioedema, skin rash and itchy skin)
Disorders of the psyche:
often:		confusion
infrequently:	psychotic reactions (in addition to hallucinations), including delirium, delirium, paranoia	psychotic reactions (in addition to hallucinations), including delirium, delirium, paranoia
frequency unknown	violation of impulse control, including pathological attraction to gambling, hypersexuality, increased libido, an irresistible attraction to shopping, compulsive overeating	violation of impulse control, including pathological attraction to gambling, hypersexuality, increased libido, an irresistible attraction to shopping, compulsive overeating
Impaired nervous system:
Often	fainting	drowsiness
infrequently	severe drowsiness and episodes of sudden falling asleep **	severe drowsiness and episodes of sudden falling asleep **
Vascular disorders:
infrequently	orthostatic hypotension, lowering blood pressure (rarely severe)	orthostatic hypotension, lowering blood pressure (rarely severe)
Disorders from the gastrointestinal tract:
Often		nausea
often	Vomiting, heartburn, abdominal pain	heartburn
Disorders from the liver and bile ducts:
frequency unknown	abnormal liver function (mainly, an increase in the activity of "hepatic" enzymes)	abnormal liver function (mainly, an increase in the activity of "hepatic" enzymes)
General disorders and disorders at the site of administration:
often	swelling of the feet

** Treatment with rhinioriol caused the development of drowsiness and was rarely accompanied by severe drowsiness and episodes of sudden falling asleep.

Violation of impulse control (disorders of habits and drives) pathological attraction to gambling, increased libido, hypersexuality, an irresistible attraction to shopping, compulsive overeating, may occur in patients using dopamine receptor agonists, including Rolprin® CP (see section "Special instructions").

Overdose:

Symptoms: In general, the symptoms of overdose are associated with dopaminergic activity (nausea, vomiting, dizziness, drowsiness).

Treatment: antagonists of dopamine receptors, such as typical neuroleptics and metoclopramide.

Interaction:

There was no pharmacokinetic interaction between ropinirole and levodopa or domperidone, which would require a change in the doses of these drugs. Neuroleptics and other centrally acting dopamine receptor antagonists, such as sulpiride or metoclopramide, can reduce the effectiveness of ropinirole, therefore, simultaneous use of these drugs should be avoided. In patients receiving high doses of estrogens, an increase in the concentration of ropinirole in the blood plasma was noted. In women who are already receiving hormone replacement therapy (HRT) prior to starting ropinirole treatment, dose adjustment of ropinirole is not required. However, in case of HRT administration or its cancellation with ropinirole treatment, it may be necessary to adjust the dose of Rolprin® SR preparation.

Ropinirole is mainly metabolized by isoenzyme CYP1A2. When

simultaneous application of ropinirole (at a dose of 2 mg three times daily) with

ciprofloxacin C_m_Oh and AUC ropinirole by 60% and 84%,

accordingly, which can lead to the development of undesirable phenomena. In this regard, in patients receiving ropinirole, its dose should be adjusted by prescribing or eliminating preparations inhibiting isoenzyme CYP1A2, such as: ciprofloxacin, enoxacin or fluvoxamine.

The pharmacokinetic interaction between ropinirole (at a dose of 2 mg three times daily) and theophylline, which is a substrate of the isoenzyme CYP1A2, in patients with Parkinson's disease is not noted.

Nicotine increases the activity of the isoenzyme CYP1A2. If the patient stops or starts smoking during treatment with ropinirole, it may be necessary to adjust his dose.

Special instructions:

Given the risk of developing arterial hypotension, in patients with severe cardiovascular insufficiency (in particular, with ischemic heart disease) it is recommended to monitor blood pressure, especially at the beginning of treatment. Simultaneous use with antihypertensive and antiarrhythmic drugs has not been studied.Caution should be exercised when using these drugs at the same time, because the risk of developing arterial hypotension, bradycardia, or other arrhythmias is not known.

Patients with psychotic disorders or their presence in an anamnesis should be prescribed dopamine receptor agonists only in cases where the expected use benefit exceeds the potential risk.

Patients should be warned about the possible development of drowsiness or episodes of sudden falling asleep, especially in patients with Parkinson's disease. Episodes of sudden falling asleep during the day, in some cases without precursors, were noted infrequently. In the case of such reactions, consideration should be given to the possibility of reversing therapy.

Violation of impulse control (disorders of habits and drives)

It is necessary to regularly monitor the possibility of impulse control violations. Patients and their caregivers should be informed that, when dopamine receptor agonists, including ropinirole, are used, behavioral manifestations of a disorder of impulsive control are possible, for example, pathological attraction to gambling, increased libido, hypersexuality, an irresistible attraction to shopping, compulsive overeating .Impairment of impulse control is usually reversible after dose reduction or drug withdrawal. If such symptoms appear, it is advisable to reduce the dose of ropinirole or gradually stop using it.

Rolprin® preparation CP is available in the form of extended-release tablets coated with a film coating, 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 to the stool.

Special information on excipients

Rolprin® preparation CP contains lactose, therefore it is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

Effect on the ability to drive transp. cf. and fur:

Patients should be warned about possible unwanted reactions during ropinirole therapy. Patients should be informed that there are very rare cases of development of episodes of sudden falling asleep without any precursors and cases of dizziness (up to vertigo).

If the patient develops drowsiness during the day and / or there are episodes of sudden falling asleep during the day, requiring active intervention, the patient must be warned that he should not drive the car and should avoid other activities requiring a high rate of psychomotor reactions.

Form release / dosage:

Tablets of prolonged action, film-coated, 2 mg, 4 mg and 8 mg.

Packaging:

For 7 or 10 tablets in a blister of the combined material polyamide / aluminum foil / PVC - aluminum foil (OPA / A1 / PVC-A1).

For 4, 8, 12 blisters (7 tablets) or 3, 6, 9 blisters (10 tablets each) are placed in a pack of cardboard together with instructions for use.

Storage conditions:At temperatures not higher than 30 ° C, in the original packaging. Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002366

Date of registration:11.02.2014

Date of cancellation:2019-02-11

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp12.06.2016

Illustrated instructions

Instructions

Rolprina® SR (Rolprina® SR)