Cyndanol® (Sindranol®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceRopiniroleRopinirole
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    • Dosage form: & nbspTlong-acting aberrations covered with a film sheath.
    Composition:On 1 tablet:

    Active substance: ropinirole hydrochloride 2.28 / 4.56 / 9.121 mg, which corresponds to ropinirole 2/4/8 mg.

    Excipients: methyl methacrylate, trimethylammonioethyl methacrylate chloride and ethyl acrylate copolymer [2: 0.1: 1] 5.28 / 10.56 (21.12 mg; hypromellose 89,955 / 179,91 / 359,819 mg; sodium lauryl sulfate 6.75 / 13.5 / 27 mg; Copovidone 44.64 / 89.28 / 178.56 mg; magnesium stearate 1.095 / 2.19 / 4.38 mg.

    Shell: opadrai II pink 32K14834 (4,5 mg) / opadrai yellowish brown OY-27207 (9 mg) / opadray red 03B25227 (18 mg).

    Opaprai II pink 32K14834: lactose monohydrate 40% (1.8 mg); hypromellose-2910 (hypromellose-15sP) 28% (1.26 mg); titanium dioxide 23,46% (1.0557 mg); triacetin 8% (0.36 mg); ferric oxide red oxide 0.54% (0.0243 mg).

    Fall yellowish brown OY-27207: hypromellose-2910 (hypromellose-6sP) 62.5% (5.625 mg); titanium dioxide 21.25% (1.9125 mg); dye sunset sunset yellow, aluminum varnish (FD&C yellow # 6) (E110) 9% (0.81 mg); Macrogol-400 6.25% (0.5625 mg); indigo carmine, aluminum lacquer (FD&C blue # 2) (E132) 1% (0.09 mg).

    Rip off the red 03B25227: hypromellose-2910 (hypromellose-bsR) 62.5% (11.25 mg); titanium dioxide24.19% (4.3542 mg); Macrogol-400 6.25% (1.125 mg); ferric oxide red oxide 6.14% (1.105 mg); ferric oxide black oxide 0.89% (0.1602 mg); dye iron oxide yellow 0.03% (0.0054 mg).

    Description:

    Tablets 2 mg: Round, biconvex tablets, covered with a film shell of pink color. Fla The cross section of the nucleus is almost white.

    Tablets 4 mg: Oblong, biconvex tablets covered with a film coating of light brown color. On the cross section, the nucleus is almost white.

    Tablets 8 mg: Oblong, biconvex tablets covered with a film coat of a reddish-brown color. On the cross section, the nucleus is almost white.

    Pharmacotherapeutic group:antiparkinsonian means - 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 non -ergoline agonist D2-, D3dopamine receptors, which has a peripheral and central effect.

    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 on the hypothalamus and pituitary levels, inhibiting the secretion of prolactin.

    Ropinirole enhances the effects of levodopa, including controlling the frequency of the on / off phenomenon and the end-of-dose effect associated with prolonged 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 boundary of the unilateral 95% confidence interval (CI) 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 oral administration is approximately 50% (36% -57%). After ingestion of ropinirole in prolonged-action tablets, its concentration in the blood plasma rises slowly. The mean time to reach the maximum concentration of the drug in the blood plasma (TSmOh) 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 fasting, an increase in the system exposure of ropinirole was observed. At the same time, an increase in the area under the concentration-time curve (AUC) (90% CI [1.12, 1.28] and the maximum concentration of the drug in the blood plasma (CmOh) (90% CI [1,34, 1,56]) on average by 20% and 44% respectively, and TFROMmOh extended for 3 hours System exposure of ropinirole with the use of long-acting tablets corresponds to systemic exposure when taking immediate-release tablets inthe same daily dose.

    Distribution

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

    Biotransformation

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

    Excretion

    Half-life (T1/2) ropinirole from the systemic blood flow averages about 6 hours. The increase in the duration of the systemic effect of ropinirole (AUC and CmOh) is approximately proportional to the dose increase. There is no difference in the excretion of ropinirole after a single dose inward or with regular use.

    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 CmOh was 30-55%, AUC - 40-70%.

    Linearity / nonlinearity

    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).

    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 and 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 who need dopaminergic therapy to delay the prescription of drugs of levodopa.

    - 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 therapy with levodopa, and to reduce the daily dose of levodopa.

    Contraindications:

    - Hypersensitivity to ropinirole or any of the components that make up the drug;

    - renal failure of severe degree (creatinine clearance (CK) <30 ml / min) in patients not receiving treatment with chronic hemodialysis;

    - impaired liver function;

    - age to 18 years;

    - the period of breastfeeding;

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

    Carefully:

    With caution appoint ropinirole patients with serious diseases of the cardiovascular system and with severe cardiovascular insufficiency.

    Ropinirole can be prescribed to patients with psychotic disorders in an anamnesis only if the expected benefit from 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 the drug in pregnancy is possible if the potential benefit to the mother exceeds the risk to the fetus.

    Do not use during breastfeeding, as it can inhibit lactation.

    Dosing and Administration:

    Take inside. Cindranol® should be taken once a day at the same time, regardless of food intake. Patients to achieve the required dose of ropinirole is recommended to take a minimum number of tablets of prolonged action, using the maximum possible dosage of tablets of the drug. In some patients, simultaneous use with fatty foods can increase AUC and / or CmOh in 2 times.

    Cindranol® tablets should be swallowed whole. Do not chew or divide into parts, as 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 Sindranol® is 2 mg once daily for 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 Cindranol® 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 the drug Sindranol® at a dose of 8 mg / day is not enough expressed or is unstable, you can continue increasing the daily dose of the drug by 2-4 mg every 2 weeks or at longer intervals (until the desired therapeutic effect is achieved). The maximum daily dose is 24 mg in one session.

    Combination Therapy

    With the simultaneous use of Cindranol® in doses,used with 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 case of switching from therapy with another dopamine receptor agonist to the Cindranol® preparation, it is necessary to follow the recommendations regarding the cancellation of the previously taken drug.

    Abolition of therapy

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

    Switching from ropinirole tablets with immediate release to prolonged-action tablets Cindranol®

    Patients can be immediately transferred from the therapy with ropinirole tablets with the immediate release of prolonged-action Cindranol® tablets. The dose of ropinirole in Cindranol® should match the daily intake of ropinirole in immediate-release tablets.The recommended appropriate doses of Cindranol® (sustained-release tablets) in case of transition from immediate-release ropinirole tablets are shown in the table below. When taking another dose of immediate-release ropinirole tablets not listed in the table, the patient should be transferred to the nearest dose indicated in the table:

    Ropinirole, immediate release tablets

    Daily dose (mg)

    Ropinirole, prolonged-release tablets (Cindranol® preparation)

    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, later the dose can be adjusted depending on the therapeutic response (see subsections "Initial dose selection" and "Treatment Scheme").

    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. Correction of dose in this category of patients is not required.

    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 (CK <30 ml / min), not receiving treatment with chronic (chronic) hemodialysis, the use of ropinirole has not been studied.

    Side effects:

    The undesirable reactions presented below are listed in accordance with the damage to organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: very often: ≥1 / 10; often: from ≥1 / 100 to <1/10; infrequently: from ≥1 / 1000 to <1/100; rarely: from ≥1 / 10,000 to <1/1000; very rarely: <1/10 000; frequency is unknown: can not be estimated from the available data.

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

    Clinical Trials Data

    The table lists unwanted reactions that occur at a higher frequency with ropinirole compared to placebo or a higher or comparable frequency with respect to the reference drug.

    Frequency of occurrence of undesirable reactions

    Undesirable reactions and frequency of their development

    Monotherapy

    Simultaneous use with levodopa

    Disorders of the psyche

    often

    hallucinations

    hallucinations, confusion

    Disturbances from the nervous system

    Often

    drowsiness

    dyskinesia (in patients with progressive form of Parkinson's disease receiving ropinirole in combination with drugs levodopa, during the titration of the dose of ropinirole may develop a violation of coordination of movements; according to clinical studies, lowering the dose of levodopa can lead to a decrease in the severity of dyskinesia)

    often

    dizziness (including vertigo)

    drowsiness, dizziness (including vertigo)

    Vascular disorders

    often

    orthostatic hypotension, hypotension

    infrequently

    orthostatic hypotension, hypotension

    Disturbances from the gastrointestinal tract (GIT)

    Often

    nausea

    often

    abdominal pain, indigestion, vomiting, constipation

    nausea, constipation

    General disorders and disorders at the site of administration

    often

    peripheral edema (including edema of the legs)

    peripheral edema

    Post-registration data

    Undesirable reactions and frequency of their development

    Monotherapy

    Simultaneous use with levodopa

    Immune system disorders

    rarely

    hypersensitivity reactions (including urticaria, angioedema, skin rash and skin itching)

    hypersensitivity reactions (including urticaria, angioedema, skin rash and skin itching)

    Disorders of the psyche

    often

    confusion

    infrequently

    psychotic reactions (excluding hallucinations), including delirium, delirium, paranoia;

    psychotic reactions (excluding hallucinations), including delirium, delirium, paranoia;

    frequency unknown

    impulsive instincts syndrome, increased libido, including craving for gambling, hypersexuality, irresistible attraction to shopping, eating, aggression *

    impulsive instincts syndrome, increased libido, including craving for gambling, hypersexuality, irresistible attraction to shopping, eating, aggression *

    Disturbances from the nervous system

    Often

    fainting

    drowsiness

    rarely

    severe drowsiness and episodes of sudden falling asleep **

    severe drowsiness and episodes of sudden falling asleep **

    Vascular disorders

    often

    orthostatic hypotension, hypotension ***

    orthostatic hypotension, hypotension ***

    Disorders from the digestive tract

    Often

    nausea

    often

    Vomiting, heartburn, abdominal pain

    heartburn

    Disturbances from the liver and bile ducts

    frequency unknown

    violations of the liver (mainly, increased activity of "liver" enzymes)

    violations of the liver (mainly, increased activity of "liver" enzymes)

    General disorders and disorders at the site of administration

    often

    swelling of the feet

    * Aggression is associated with psychotic reactions and compulsive symptoms.

    ** As with other dopaminergic agents, pronounced sleepiness and episodes of sudden falling asleep were very rarely reported, especially in patients with Parkinson's disease in 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 the symptoms disappeared. In most cases, associated sedatives were used).

    *** As with other dopaminergic agents, hypotension was observed with ropinirole, including orthostatic hypotension.

    Violation of impulse control (disorders of habits and drives)

    A pathological attraction to gambling, increased libido, hypersexuality, an irresistible attraction to shopping, compulsive overeating may occur in patients using dopamine receptor agonists, including Cyndanol® (see section "Special instructions").

    Overdose:

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

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

    Interaction:

    There was no pharmacokinetic interaction between ropinirole and levodopa or domperidone, which would require correction of 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 have already received hormone replacement therapy (HRT) prior to starting ropinirole treatment, no dose adjustment for ropinirole is required. However, in the event that HRT is prescribed or canceled, with ropinirole treatment, a dose adjustment of Cindranol® may be required.

    Ropinirole is mainly metabolized by isoenzyme CYP1A2. With the simultaneous use of ropinirole (at a dose of 2 mg three times daily) with ciprofloxacin, the indices FROMmax and AUC ropinirole by 60% and 84% respectively, which can lead to the development of undesirable phenomena. In this regard, patients receiving ropinirole, its dose should be adjusted by prescribing or eliminating preparations inhibiting isoenzyme CYP1A2, such as ciprofloxacin, enoxacin or fluvoxamine.

    In patients with Parkinson's disease who were taking concomitantly digoxin, there was no interaction of digoxin with ropinirole, which would require correction of doses. The pharmacokinetic interaction between ropinirole (at a dose of 2 mg three times daily) and theophylline, which is a substrate of the isoenzyme CYP1A2, patients with Parkinson's disease were not observed.

    There is no information on the possible interaction of ropinirole and alcohol. As with other central drugs, patients should be warned about the need to refrain from drinking alcohol during ropinirole treatment.

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

    Special instructions:

    Given the risk of developing arterial hypotension in patients with severe cardiovascular insufficiency (in particular, with coronary 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. Care should be taken when usingthese drugs, since the risk of developing arterial hypotension, bradycardia or other arrhythmias is unknown.

    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, sometimes without previous drowsiness. In the case of such reactions, consideration should be given to the possibility of reversing ropinirole 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, with the use of dopamine receptor agonists, including ropinirole, the development of a syndrome of impulsive drives, including compulsive behavior, including pathological attraction to gambling, increased libido, hypersexuality, an irresistible attraction to shopping , binge eating. Attraction disorders, as a rule, are reversible after dose reduction or drug withdrawal.

    In some cases with the use of ropinirole other risk factors may be compulsive behavior in the history or the combined use of several dopaminergic drugs. In this case, you should consider the possibility of reducing the dose or canceling therapy.

    Paradoxical worsening of restless leg syndrome was noted with ropinirole therapy (earlier onset, increased intensity of manifestation, or progression of symptoms with the capture of previously unaffected limbs), or rebound syndrome (relapse of symptoms) in the early morning hours (relapse of symptoms in the early morning hours) . When these symptoms appear, it is necessary to revise the tactics of treatment with ropinirole, to clarify the dosage right up to the possible withdrawal of the drug.

    The preparation Cindranol® 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 digestive tract, there is a risk of incomplete release of the drug substance and passing its residue into a stool.

    Special information on excipients

    The drug 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 14 tablets in a blister of PVC / PCTFE // aluminum foil.

    2, 4 or 6 blisters together with instructions for use in a cardboard bundle.

    Storage conditions:

    At a temperature of no higher than 25 ° C.

    Indication of the need for storage of medicinal products in places inaccessible to children.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003786
    Date of registration:12.08.2016
    Expiration Date:12.08.2021
    The owner of the registration certificate:EGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary
    Manufacturer: & nbsp
    Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary
    Information update date: & nbsp07.09.2016
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