Composition, form of production and packaging
The tablets of prolonged action, covered with a film membrane of pink color, capsular form, biconcave, with engraving "GS" on one side and "3V2" on the other.
1 tab.
ropinirole hydrochloride * 2.28 mg,
which corresponds to the content of ropinirole 2 mg
[PRING] upper barrier layer **: hypromellose 2208-62.83 mg, glyceryl dibeganate 35 mg, mannitol 33.04 mg, povidone K29-32-7 mg, magnesium stearate 1.4 mg, silicon dioxide colloid 0.56 mg, iron III ) oxide (yellow) - 0.17 mg; active layer: hypromellose 2208-61.5 mg, lactose monohydrate 46.32 mg, carmellose sodium 15 mg, hydrogenated castor oil 15 mg, maltodextrin 7.5 mg, magnesium stearate 1.5 mg, silicon dioxide colloid 0.9 mg; the lower barrier layer **: hypromellose 2208 - 76.29 mg, glyceryl dibeganate 42.5 mg, mannitol 40.12 mg, povidone K29-32 8.5 mg, magnesium stearate 1.7 mg, silicon colloidal dioxide 0.68 mg, iron (III) oxide yellow) - 0.21 mg.
The composition of the film sheath: dye opener OY-S-24900 pink - 13.8 mg (hypromellose 2910 - 66%, titanium dioxide 27%, macrogol 400-6.6%, iron (II) oxide (red) 0.25%, iron (III) oxide (yellow) - 0.15%).
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (6) - packs of cardboard.
21 pcs. - blisters (2) - packs of cardboard.
Long-acting tablets coated with a film -colored coating of light brown color, capsular shaped, biconcave, engraved "GS" on one side and "WXG" on the other.
1 tab.
ropinirole hydrochloride * 4.56 mg,
which corresponds to the content of ropinirole 4 mg
[PRING] upper barrier layer **: hypromellose 2208-62.83 mg, glyceryl dibeganate 35 mg, mannitol 33.04 mg, povidone K29-32-7 mg, magnesium stearate 1.4 mg, silicon dioxide colloid 0.56 mg, iron III ) oxide (yellow) - 0.17 mg; active layer: hypromellose 2208 - 61.5 mg, lactose monohydrate - 44.04 mg, carmellose sodium - 15 mg, hydrogenated castor oil - 15 mg, maltodextrin - 7.5 mg, magnesium stearate - 1.5 mg, silicon dioxide colloid - 0.9 mg; the lower barrier layer **:hypromellose 2208 - 76.29 mg, glyceryl dibeganate 42.5 mg, mannitol 40.12 mg, povidone K29-32 8.5 mg, magnesium stearate 1.7 mg, silicon colloidal dioxide 0.68 mg, iron (III) oxide yellow) - 0.21 mg.
The composition of the film shell: opedrai colorant OY-27207 light brown - 13.8 mg (hypromellose 2910 - 62.5%, titanium dioxide - 21.25%, macrogol 400 - 6.25%, dye sunset yellow - 9%, indigo carmine - 1%).
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (6) - packs of cardboard.
The tablets of prolonged action, covered with a film shell of red color, capsular form, biconcave, with engraving "GS" on one side and "5CC" on the other.
1 tab.
ropinirole hydrochloride * 9.12 mg,
which corresponds to the content of ropinirole 8 mg
[PRING] upper barrier layer **: hypromellose 2208-62.83 mg, glyceryl dibeganate 35 mg, mannitol 33.04 mg, povidone K29-32-7 mg, magnesium stearate 1.4 mg, silicon dioxide colloid 0.56 mg, iron III ) oxide (yellow) - 0.17 mg; active layer: hypromellose 2208 - 61.5 mg, lactose monohydrate 39.48 mg, carmellose sodium 15 mg, hydrogenated castor oil 15 mg, maltodextrin 7.5 mg, magnesium stearate 1.5 mg, silicon colloidal dioxide 0.9 mg; the lower barrier layer **: hypromellose 2208 - 76.29 mg, glyceryl dibeganate 42.5 mg, mannitol 40.12 mg, povidone K29-32 8.5 mg, magnesium stearate 1.7 mg, silicon colloidal dioxide 0.68 mg, iron (III) oxide yellow) - 0.21 mg.
The composition of the film shell: dye opener 03B25227 red - 13.8 mg (hypromellose 2910 - 62.5%, titanium dioxide - 24.19%, macrogol 400 - 6.25%, iron (II) oxide (red) - 6.14%, iron (III) oxide (black) - 0.89%, iron (III) oxide (yellow) - 0.03%).
14 pcs. - blisters (2) - packs of cardboard.
14 pcs. - blisters (6) - packs of cardboard.
* equivalent to the nominal dosage of ropinirole in the form of a free base.
** The composition and mass of the barrier layers are identical in tablets with different dosages.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
An antiparkinsonian drug, a highly selective nonergolin agonist of dopamine D 2 -, D 3 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. Thus, ropinirole reduces the degree of hypodynamia, rigidity and tremor, which are symptoms of parkinsonism.
Ropinirole compensates for dopamine deficiency in systems of black matter and the striatum by stimulating dopamine receptors in the striatum.
Ropinirole enhances the effects of levodopa, including monitoring the incidence of the on / off phenomenon and the end-of-dose effect associated with prolonged therapy with levodopa preparations, and allows to reduce the daily dose of levodopa.
Ropinirole has an effect on the hypothalamus and pituitary levels, inhibiting the secretion of prolactin.
PHARMACOKINETICS
The pharmacokinetics of ropinirole is similar in healthy people, patients with Parkinson's disease and patients with restless legs syndrome and varies depending on the dosage form.
Suction
After oral administration, the bioavailability of ropinirole is low and is approximately 50% (36-57%). After ingestion of ropinirole in sustained release tablets, its plasma concentration rises slowly, the mean time T max is 6 hours. In patients with Parkinson's disease after ingestion of ropinirole at a dose of 12 mg 1 time / day in combination with a diet rich in fats in an equilibrium the increase in the system exposure of ropinirole was observed, with an increase in AUC and C max of 20% and 44%, respectively, of T max was extended by 3 hours. However, in clinical trials of efficacy and safety, ropinirole was taken regardless of t food intake.
The increase in the duration of systemic action of ropinirole (C max and AUC) is approximately proportional to the increase in dose.
Distribution
Binding to blood plasma proteins is low (10-40%). Due to its high lipophilicity, ropinirole is characterized by a large V d (approximately 7 l / kg).
Metabolism
Ropinirole is mainly metabolized by the isoenzyme CYP1A2.
Excretion
On average, T 1/2 ropinirole from the systemic blood flow is about 6 hours. The ropinirole metabolite is mainly excreted by the kidneys. There is no difference in the excretion of ropinirole after a single dose inwards or with regular use.
Pharmacokinetics in special clinical cases
The clearance of ropinirole after ingestion is reduced by approximately 15% in elderly patients (65 years and older) compared with younger patients. Dose adjustments are not required for this category of patients.
Pharmacokinetic parameters do not change in patients with impaired renal function of mild and moderate degree and Parkinson's disease. In patients with a terminal stage of renal failure who are on permanent hemodialysis, the clearance of ropinirole during ingestion is reduced by approximately 30%.
INDICATIONS
Parkinson's disease:
- monotherapy of early stages of the disease in patients in need of dopaminergic therapy in order to delay the appointment of levodopa preparations;
- as part of combination therapy in patients receiving levodopa preparations in order to increase the effectiveness of levodopa, including 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, dose of levodopa.
DOSING MODE
The drug is administered orally 1 time / day at the same time, regardless of food intake. Tablets take whole, not liquid, not breaking.
Individual selection of the dose is recommended in accordance with the efficacy and tolerability of the drug.
It is recommended that the dose be reduced in the event that the patient experiences drowsiness at any stage of dose selection. When developing other unwanted reactions, it is necessary to reduce the dose of the drug followed by a gradual increase in the dose.
It should be borne in mind the need for titration dose when passing a dose (one or more).
Monotherapy
Start treatment
The recommended initial dose of Rekvip Modabat В® is 2 mg 1 time / day for one week. Subsequently, the dose is increased by 2 mg at intervals of at least 1 week to 8 mg / day.
Week 1 2 3 4
Daily dose (mg) 2 4 6 8
Maintenance dose
If, after choosing a dose, the therapeutic effect is not sufficiently pronounced or unstable, you can continue increasing the daily dose of the drug by 4 mg at intervals of 1-2 weeks (until the desired therapeutic effect is achieved). The dose can be changed depending on the therapeutic effect and increased to a maximum dose of 24 mg 1 time / day.
Combination Therapy
When using Rekvip Modabut В® in doses used in monotherapy, in combination with levodopa preparations, the dose of levodopa can be gradually reduced (depending on the clinical effect). In clinical trials in patients simultaneously receiving Rekvip Modabut В® in sustained-release tablets, the dose of levodopa was gradually reduced by approximately 30%. Patients with a progressive form of the disease who are taking Rekvip Modatab В® in combination with levodopa preparations may experience dyskinesia during the titration dose of ropinirole. Reducing the dose of levodopa medications can lead to a decrease in this symptomatology.
Abolition of therapy. Rekvip Modatab В® (like other dopaminergic drugs) should be canceled, gradually reducing the daily dose for at least 1 week. If treatment was interrupted for 1 day or more, then when resumption of therapy should consider the need for titration dose.
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 is carried out as usual.
In patients with impaired renal function of mild and moderate severity (CK 30-50 ml / min), the clearance of ropinirole does not change, correction of the dose of ropinirole is not required.
For patients with end-stage renal failure who are on hemodialysis, the recommended initial dose of ropinirole is 2 mg 1 time / day. The subsequent dose increase should be based on an assessment of tolerability and efficacy. The maximum daily dose in patients on chronic hemodialysis is 18 mg. The introduction of maintenance doses after hemodialysis is not required.
SIDE EFFECT
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 (? 1/100, <1/10); sometimes (? 1/1000, <1/100); rarely (? 1/10 000, <1/1000); very rarely (<1/10 000, including individual cases).
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
Frequency Application as a monotherapy Usage as part of combination therapy
Disorders of the psyche
Often hallucinations hallucinations, confusion,
From the nervous system
very often drowsiness dyskinesia 1
often dizziness (including vertigo) drowsiness, dizziness (including vertigo)
From the side of the cardiovascular system
often orthostatic hypotension, hypotension
infrequently orthostatic hypotension, hypotension
From the digestive system
very often nausea
often abdominal pain, indigestion, vomiting, constipation, nausea, constipation
General reactions
often peripheral edema (including edema of the legs) peripheral edema
1 Patients with a progressive form of the disease who are taking Rekwip Modabab in combination with levodopa preparations, during the titration period of the dose, development of a disruption of the coordination of movements is possible. It was shown that the withdrawal of levodopa medications can lead to a decrease in this symptomatology.
Post-registration data
From the immune system: very rarely - hypersensitivity reactions, including hives, angioedema, rash, itching.
Disorders of the psyche: infrequently - psychotic reactions (excluding hallucinations), including delirium, paranoia, delirium; syndrome of impulsive drives, increased libido, including hypersexuality, pathological attraction to gambling, irresistible attraction to shopping, overeating, aggression *.
From the nervous system: very rarely - marked drowsiness, episodes of sudden falling asleep **
From the cardiovascular system: often - orthostatic hypotension, hypotension ***.
Allergic reactions: very rarely - hives, angioedema, rash, itching.
* Aggression is associated with psychotic reactions and compulsive symptoms.
** As with other dopaminergic agents, pronounced synergy and episodes were reported very rarely, primarily in patients with Parkinson's disease in post-acquisition 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 withdrawn, all symptoms disappeared. In most cases, associated sedatives were used.
*** As with other dopamyergic agents, hypotension was observed with ropinirole, including orthostatic hypotension.
CONTRAINDICATIONS
- Acute psychosis;
- violations of the liver function;
- severe renal dysfunction (QC less than 30 ml / min), which does not undergo regular hemodialysis;
- rare hereditary diseases: lactose intolerance, lactase insufficiency, impaired absorption of glucose or galactose;
- Pregnancy;
- lactation;
- children and adolescence under 18;
- Hypersensitivity to the components of the drug.
Caution should be used in patients 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
Contraindicated in pregnancy and lactation (breastfeeding).
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with impaired renal function of mild and moderate severity (CK 30-50 ml / min), the clearance of ropinirole does not change, correction of the dose of ropinirole is not required.
For patients with end-stage renal failure who are on hemodialysis, the recommended initial dose of ropinirole is 2 mg 1 time / day. The subsequent increase in dose should be based on the assessment of tolerability and efficacy. The maximum daily dose in patients on chronic hemodialysis is 18 mg. The introduction of maintenance doses after hemodialysis is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindication: liver dysfunction.
APPLICATION FOR CHILDREN
Contraindicated: children and adolescence under 18 years.
APPLICATION IN 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 is carried out as usual.
SPECIAL INSTRUCTIONS
Patients should be warned about the possible development of drowsiness or episodes of sudden falling asleep, sometimes not preceded by drowsiness. In the case of such reactions, consideration should be given to the possibility of reversing therapy.
It is recommended to monitor BP because of the possibility of developing orthostatic hypotension.
In patients taking dopaminergic drugs, incl. ropinirole, reported on the syndrome of impulsive drives, including compulsive behavior, incl. pathological attraction to gambling, hypersexuality, irresistible attraction to shopping, overeating. Attraction disorders, as a rule, are reversible after dose reduction or drug withdrawal. In some cases, with the use of the drug Requak Modabab В® other risk factors may be compulsive behavior in the history or the combined use of several dopaminergic drugs.
Paradoxical worsening of restless legs syndrome was noted with ropinirole therapy (earlier onset, increased intensity of manifestation, or progression of symptoms involving previously unaffected limbs), or ricochet syndrome 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, specify the dose up to the possible withdrawal of the drug.
Prenarat Rekvip Modatab В® 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 transition of its residue to a stool
Impact on the ability to drive vehicles and manage mechanisms
Patients should be advised of possible adverse reactions during ropinirole therapy.
Patients should be informed that there are very rare cases of sudden falling asleep without any previous or obvious signs of daytime sleepiness and cases of dizziness (sometimes pronounced). If the patient develops daytime drowsiness or episodes of falling asleep during the day, requiring active intervention, the patient should be warned about the need to abandon driving and avoid other activities requiring high concentration and speed of psychomotor reactions.
OVERDOSE
Symptoms: mainly due to dopaminergic action - nausea, vomiting, dizziness, drowsiness.
Treatment: use of dopamine antagonists, such as typical neuroleptics and metoclopramide.
DRUG INTERACTION
Typical antipsychotics and other central action dopamine antagonists, such as sulpiride or metoclopramide, can reduce the effectiveness of ropinirole (simultaneous administration should be avoided).
There was no pharmacokinetic interaction between ropinirole and levodopa or domperidone, which would require correction of the doses of these drugs.
Ropinirole does not interact with other drugs that are often used to treat Parkinson's disease.
In patients with Parkinson's disease treated with digoxin at the same time, there was no interaction of digoxin with ropinirole, which would require a dose adjustment.
Ropinirole is mainly metabolized isoenzyme CYP1A2. Pharmacokinetic studies in patients with Parkinson's disease revealed that ciprofloxacin increased the C maxand AUC of ropinirole by about 60% and 84% respectively. Therefore, in patients receiving ropinirole, its dose should be adjusted in the appointment and cancellation of drugs that inhibit isozyme CYP1A2, e.g., ciprofloxacin, enoxacin or fluvoxamine.
Pharmacokinetic drug interaction study in patients with Parkinson's disease between ropinirole and theophylline, are substrates isoenzyme CYP1A2 revealed that the pharmacokinetics of drugs is not changed. With simultaneous application of ropinirole with other substrates isoenzyme CYP1A2 pharmacokinetics of ropinirole is not changed.
Increase in plasma concentrations of ropinirole was observed in patients treated with high doses of estrogen. In patients receiving hormone replacement therapy before treatment ropinirole, ropinirole treatment may be initiated in the usual way. However, in the event of a hormone replacement therapy or the beginning of her during therapy ropinirole may need a dose adjustment.
Information on interoperability ropinirole and no ethanol. As is the case with other centrally acting drugs, patients should be alerted about the need to abstain from alcohol during treatment with ropinirole.
It is well known that nicotine induces isoenzyme CYP1A2, therefore if a patient starts or stops smoking during treatment with ropinirole, it may need dose adjustment.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
RU / RPL / 0010/16, the date of creation of the material 12/16/2016
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of the reach of children, in the original package, at a temperature of no higher than 25 В° C. Shelf life for tablets 2 mg - 2 years for the tablets of 4 mg and 8 mg - 3 years.
