Requip Modutab tablets of prolonged action, p / o 2mg, No. 28

• Parkinson's disease:

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

  • As a combination therapy in patients receiving levodopa drugs, in order to increase the effectiveness of levodopa, including control of fluctuations ('on-off') and the effect of the 'end of dose' against the background of chronic levodopa therapy, as well as to reduce the daily dose of levodopa.

Adults
Inside.
'Requip Modutab' should be taken once a day at the same time, regardless of the pizza intake. Take the tablets whole, without chewing, without breaking.
The need for dose titration should be considered when a dose (one or more) is missed.
A dose reduction is recommended if the patient experiences drowsiness at any stage of dose selection.
With the development of other adverse reactions, it is necessary to reduce the dose of the drug, followed by a gradual increase in the dose.
Individual selection of the dose is recommended in accordance with the efficacy and tolerability of the drug.
Monotherapy Treatment initiation

The recommended starting dose of Requip Modutab is 2 mg once a day for one week. Subsequently, the dose is increased by 2 mg at intervals of at least 1 week to 8 mg / day.

Maintenance dose
If, after selecting the dose, the therapeutic effect is insufficiently expressed or is unstable, you can continue to increase the daily dose of the drug by 4 mg at intervals of 1-2 weeks (until the required 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 per day.

One tablet contains:
Active ingredient : ropinirole hydrochloride 2.28 mg (equivalent to 2 mg ropinirole, respectively).
Excipients : hypromellose-2208, hydrogenated castor oil, sodium carmellose, povidone-K29-32, maltodextrin, magnesium stearate, lactose monohydrate, colloidal silicon dioxide, mannitol, iron [III] oxide (yellow) (E172), glyceryl dibehenate.
Tablet shell :

In tablets with a dosage of 2 mg (pink opadry dye QY-S-24900) :
Hypromellose-2910, titanium dioxide (E171), macrogol-400, iron [II] oxide (red) (E172), iron [III] oxide (yellow) (E172)

• Hypersensitivity to ropinirole or any of the components of the drug.

• Pregnancy and lactation.

• Liver dysfunction.

• Severe renal dysfunction (creatinine clearance less than 30 ml / min), which is not carried out on a regular basis hemodialysis.

• Rare hereditary diseases: lactose intolerance, lactase deficiency, malabsorption of glucose or galactose.

• Children under the age of 18.

• Acute psychosis.

Precautions
Due to the pharmacological action of ropinirole, it should be used with caution in patients with severe cardiovascular insufficiency.
Ropinirole should only be used in patients with a history of psychotic disorder if the expected benefit outweighs the potential risk.

Trade name of the drug : Requip Modutab

International Non- Proprietary Name (INN) : ropinirole

Dosage form : tablets of prolonged action, film-coated.

Composition : One tablet contains:
Active substance : ropinirole hydrochloride 2.28 mg, 4.56 mg, 9.12 mg (equivalent to 2 mg, 4 mg, 8 mg ropinirole, respectively).
Excipients : hypromellose-2208, hydrogenated castor oil, sodium carmellose, povidone-K29-32, maltodextrin, magnesium stearate, lactose monohydrate, colloidal silicon dioxide, mannitol, iron [III] oxide (yellow) (E172), glyceryl dibegenate.
Tablet shell :
In tablets with a dosage of 2 mg (pink opadry dye QY-S-24900) :
Hypromellose-2910, titanium dioxide (E171), macrogol-400, iron [II] oxide (red) (E172), iron [III] oxide (yellow) (E172)
In tablets with a dosage of 4 mg (light brown opadry dye OY-272Q7) :
Hypromellose-2910, titanium dioxide (E171), macrogol-400, sunset yellow dye (E110), indigo carmine (E132)
In tablets with a dosage of 8 mg (red dye opadry 03¬25227)
Hypromellose-2910, titanium dioxide (E171), macrogol-400, iron [II] oxide (red) (E172), iron [H] oxide (black) (E172), iron [III] oxide (yellow) ( E172)

Description : Biconvex film-coated, capsule-shaped tablets with GS engraving on one side. The color of the tablet shell and the type of engraving on the other side are determined by the dosage:
2 mg - pink 3V2;
4 mg - light brown WXG;
8 mg - red 5——;

Pharmacotherapeutic group : antiparkinsonian agent, dopamine agonist.
ATX code N04BC04

PHARMACOLOGICAL PROPERTIES
Mechanism of action
Ropinirole is an effective and highly selective non-ergoline agonist of dopamine D2-, D3-receptors, which has peripheral and central action.
The drug does not act on the disintegrating presynaptic dopaminergic neurons of the substantia nigra and acts directly as a synthetic neurotransmitter. Thus, ropinirole reduces the degree of hypodynamia, rigidity and tremor, which are symptoms of parkinsonism.

Pharmacodynamics
Ropinirole compensates for dopamine deficiency in the substantia nigra and striatum systems by stimulating dopamine receptors in the striatum.
Ropinirole enhances the effects of levodopa, including controlling the frequency of the on / off phenomenon and the 'end-of-dose' effect associated with long-term levodopa therapy, and allows for a reduction in the daily dose of levodopa. Ropinirole acts at the level of the hypothalamus and pituitary gland, inhibiting the secretion of prolactin.

Pharmacokinetics The
pharmacokinetics of ropinirole are similar in healthy individuals, patients with Parkinson's disease, and patients with restless legs syndrome and differs depending on the dosage form.
Suction.
The bioavailability of ropinirole after oral administration is low and is approximately 50% (36% -57%). After oral administration of ropinirole in sustained-release tablets, its plasma concentration rises slowly, the average time to reach the maximum concentration (Tmax) is 6 hours. rich in fats, an increase in systemic exposure to ropinirole was observed, while there was an increase in the area under the concentration-time curve (AUC) and maximum concentration (Cmax) by 20% and 44%, respectively, Tmax was extended by 3 hours. However, in clinical studies of the efficacy and safety ropinirole was taken regardless of food intake.
Plasma protein binding and distribution... Plasma protein binding is low (10-40%). Due to its high lipophilicity, ropinirole is characterized by a large volume of distribution (approximately 7 l / kg).
Metabolism . Ropinirole is mainly metabolized by the CYP1A2 isoenzyme.
The metabolite ropinirole is mainly excreted by the kidneys.
Excretion . On average, the half-life of ropinirole from the systemic circulation is about 6 hours. The increase in the duration of the systemic effect of ropinirole (Cmax and AUC) is approximately proportional to the increase in dose. There is no difference in the elimination of ropinirole after a single oral dose or with regular use.
Special patient groups
Elderly patients
The clearance of ropinirole after oral administration is reduced by approximately 15% in elderly patients aged 65 years and older compared with younger patients. No dose adjustment is required in this category of patients.
Patients with impaired renal function
Pharmacokinetic parameters do not change in patients with mild to moderate renal impairment and Parkinson's disease.
In patients with end-stage renal failure on continuous hemodialysis, oral clearance of ropinirole decreases by about 30%.

Indications for use

• Parkinson's disease:

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

  • As a combination therapy in patients receiving levodopa drugs, in order to increase the effectiveness of levodopa, including control of fluctuations ('on-off') and the effect of the 'end of dose' against the background of chronic levodopa therapy, as well as to reduce the daily dose of levodopa.

Contraindications

• Hypersensitivity to ropinirole or any of the components of the drug.

• Pregnancy and lactation.

• Liver dysfunction.

• Severe renal dysfunction (creatinine clearance less than 30 ml / min), which is not carried out on a regular basis hemodialysis.

• Rare hereditary diseases: lactose intolerance, lactase deficiency, malabsorption of glucose or galactose.

• Children under the age of 18.

• Acute psychosis.

Precautions
Due to the pharmacological action of ropinirole, it should be used with caution in patients with severe cardiovascular insufficiency.
Ropinirole should only be used in patients with a history of psychotic disorder if the expected benefit outweighs the potential risk.

Method of administration and dosage
Adults
Inside.
'Requip Modutab' should be taken once a day at the same time, regardless of the pizza intake. Take the tablets whole, without chewing, without breaking.
The need for dose titration should be considered when a dose (one or more) is missed.
A dose reduction is recommended if the patient experiences drowsiness at any stage of dose selection.
With the development of other adverse reactions, it is necessary to reduce the dose of the drug, followed by a gradual increase in the dose.
Individual selection of the dose is recommended in accordance with the efficacy and tolerability of the drug.
Monotherapy Treatment initiation

The recommended starting dose of Requip Modutab is 2 mg once a day for one week. Subsequently, the dose is increased by 2 mg at intervals of at least 1 week to 8 mg / day.

Maintenance dose
If, after selecting the dose, the therapeutic effect is insufficiently expressed or is unstable, you can continue to increase the daily dose of the drug by 4 mg at intervals of 1-2 weeks (until the required 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 per day.
Combination therapy
When using the drug 'Requip Modutab' in doses used in monotherapy, in combination with levodopa drugs, the dose of levodopa can be gradually reduced (depending on the clinical effect). In clinical studies in patients simultaneously receiving 'Requip Modutab' in sustained-release tablets, the dose of levodopa was gradually reduced by approximately 30%. In patients with a progressive form of the disease, taking 'Requip Modutab' in combination with levodopa drugs, dyskinesia may occur during the titration period of ropinirole. Reducing the dose of levodopa drugs can lead to a decrease in these symptoms.
Cancellation of therapy
As in the case with other dopaminergic drugs, 'Requip Modutab' should be canceled, gradually reducing the daily dose for at least 1 week. If treatment was interrupted for 1 day or longer, then the need for dose titration should be considered when resuming therapy.
Special patient groups
Elderly patients
Despite a possible decrease in drug clearance in patients aged 65 years and older, titration of the dose of ropinirole in this category of patients is carried out as usual.
Patients with impaired renal function
Impaired renal function of mild and moderate severity
In patients with impaired renal function of mild and moderate severity (creatinine clearance 30-50 ml / min), the clearance of ropinirole does not change, dose adjustment of ropinirole is not required.
Patients with end-stage renal failure on hemodialysis The
recommended starting dose of ropinirole is 2 mg once daily.
Subsequent dose increases should be based on an assessment of tolerability and efficacy. The maximum daily dose in patients on continuous hemodialysis is 18 mg. The introduction of maintenance doses after hemodialysis is not required.

Overdose
Symptoms
Basically, the symptoms of ropinirole overdose are associated with dopaminergic effects (nausea, vomiting, dizziness, drowsiness).
Treatment
These symptoms can be corrected by appropriate treatment with dopamine antagonists such as typical antipsychotics and metoclopramide.

Interaction with other drugs
Typical antipsychotics and other centrally acting dopamine antagonists, such as sulpiride or metoclopramide, can reduce the efficacy of ropinirole and, therefore, concomitant administration of these drugs with ropinirole should be avoided.
There was no pharmacokinetic interaction between ropinirole and levodopa or domperidone, which would require dose adjustment of these drugs. Ropinirole does not interact with other drugs commonly used to treat Parkinson's disease.
In patients with Parkinson's disease, taking simultaneously digoxin, there was no interaction of digoxin with ropinirole, which would require dose adjustment.
Ropinirole is mainly metabolized by the CYP1A2 isoenzyme of the cytochrome P450 enzyme system. Pharmacokinetic studies in patients with Parkinson's disease have shown that ciprofloxacin increases the Cmax and AUC of ropinirole by approximately 60% and 84%, respectively. In connection with. Therefore, in patients receiving ropinirole, its dose should be adjusted when prescribing and discontinuing drugs that inhibit the CYP1A2 isoenzyme, for example, ciprofloxacin, enoxacin or fluvoxamine.
Pharmacokinetic study of drug interactions in patients with Parkinson's disease between ropinirole and theophylline, which is a substrate of the CYP1A2 isoenzyme, showed that the pharmacokinetics of the drugs did not change.
In this connection, with the simultaneous use of ropinirole with other substrates of the CYP1A2 isoenzyme, the pharmacokinetics of ropinirole does not change.
An increase in plasma concentration of ropinirole was observed in patients receiving high doses of estrogens. In patients receiving hormone replacement therapy prior to starting ropinirole, ropinirole may be started as usual. However, if hormone replacement therapy is discontinued or started during ropinirole therapy, dose adjustment may be required.
There is no information on the possibility of interaction between ropinirole and alcohol. As with other centrally acting drugs, patients should be advised to refrain from alcohol during treatment with ropinirole.
Nicotine is known to induce the CYP1A2 isoenzyme, so dose adjustments may be required if the patient starts or stops smoking during treatment with ropinirole.

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 event of such reactions, the possibility of discontinuation of therapy should be considered. Blood pressure monitoring is recommended because of the potential for orthostatic hypotension.
Desire disorders, including compulsive behaviors such as pathological gambling and hypersexuality, have been reported in patients taking dopaminergic drugs, including ropinirole. According to the literature, similar undesirable effects of therapy were observed in patients with Parkinson's disease receiving high doses of dopaminergic drugs; other risk factors may be a history of compulsive behavior or the combined use of several dopaminergic drugs. In this case, the possibility of reducing the dose or discontinuing therapy should be considered.
Paradoxical deterioration in restless legs syndrome was observed with ropinirole therapy (earlier onset, increased intensity of manifestations, or progression of symptoms with seizure of previously unaffected limbs), or rebound syndrome in the early morning hours (recurrence of symptoms in the early morning hours). When these symptoms appear, it is necessary to reconsider the tactics of treatment with ropinirole, to clarify the dosage up to the possible cancellation of the drug.

Influence on the ability to drive a car and / or other mechanisms
Patients should be warned of possible adverse reactions during ropinirole therapy.
Patients should be informed that there are very rare cases of sudden falling asleep episodes without any previous or obvious signs of daytime sleepiness and cases of dizziness (sometimes pronounced).
If the patient develops daytime sleepiness or episodes of falling asleep during the day that require active intervention, the patient should be warned not to drive a car and should avoid other activities that require a high speed of psychomotor reactions and attention.

Release form
Tablets of prolonged action, film-coated, 2 mg, 4 mg and 8 mg each.
21 tablets with a dosage of 2 mg in a blister made of PVC / A1 or PCTFE / A1. 2 blisters together with instructions for use in a cardboard box.
14 tablets (all dosages) in a PVC / A1 or PCTFE / A1 blister. 2 or 6 blisters with instructions for use in a cardboard box.

Shelf life
3 years - for dosages of 4 mg, 8 mg;
2 years - for a dosage of 2 mg.
Do not use after the expiry date stated on the package.

Storage conditions
In the original packaging at a temperature not exceeding 25 ? C.
Keep out of the reach of children.

Conditions of dispensing from pharmacies

On prescription