Rekvip модутаб

General characteristics. Structure:

Tablets of the prolonged action, film coated pink color, a kapsulovidny form, biconvex, with an engraving of "GS" on one party and "3V2" - on another.

Active ingredient: a ropinirola a hydrochloride of 2.28 mg that corresponds to the maintenance of a ropinirol of 2 mg

Excipients: upper barrier layer: a gipromelloza of 2208 - 62.83 mg, glyceryl дибеганат - 35 mg, Mannitolum - 33.04 mg, K29-32 povidone - 7 mg, magnesium stearate - 1.4 mg, silicon dioxide colloid - 0.56 mg, gland (III) oxide (yellow) - 0.17 mg; active layer: a gipromelloza of 2208 - 61.5 mg, lactoses monohydrate - 46.32 mg, a karmelloza of sodium - 15 mg, the castor oil hydrogenated - 15 mg, maltodextrin - 7.5 mg, magnesium stearate - 1.5 mg, silicon dioxide colloid - 0.9 mg; lower barrier layer: a gipromelloza of 2208 - 76.29 mg, glyceryl дибеганат - 42.5 mg, Mannitolum - 40.12 mg, K29-32 povidone - 8.5 mg, magnesium stearate - 1.7 mg, silicon dioxide colloid - 0.68 mg, gland (III) oxide (yellow) - 0.21 mg.

Structure of a film cover: dye опадрай pink OY-S-24900 - 13.8 mg (a gipromelloza of 2910 - 66%, titanium dioxide - 27%, a macrogoal of 400 - 6.6%, iron (II) oxide (red) - 0.25%, gland (III) oxide (yellow) - 0.15%).

Tablets of the prolonged action, film coated light brown color, a kapsulovidny form, biconvex, with an engraving of "GS" on one party and "WXG" - on another.

Active ingredient: a ropinirola a hydrochloride of 4.56 mg that corresponds to the maintenance of a ropinirol of 4 mg

Excipients: upper barrier layer: a gipromelloza of 2208 - 62.83 mg, glyceryl дибеганат - 35 mg, Mannitolum - 33.04 mg, K29-32 povidone - 7 mg, magnesium stearate - 1.4 mg, silicon dioxide colloid - 0.56 mg, gland (III) oxide (yellow) - 0.17 mg; active layer: a gipromelloza of 2208 - 61.5 mg, lactoses monohydrate - 44.04 mg, a karmelloza of sodium - 15 mg, the castor oil hydrogenated - 15 mg, maltodextrin - 7.5 mg, magnesium stearate - 1.5 mg, silicon dioxide colloid - 0.9 mg; lower barrier layer: a gipromelloza of 2208 - 76.29 mg, glyceryl дибеганат - 42.5 mg, Mannitolum - 40.12 mg, K29-32 povidone - 8.5 mg, magnesium stearate - 1.7 mg, silicon dioxide colloid - 0.68 mg, gland (III) oxide (yellow) - 0.21 mg.

Structure of a film cover: dye опадрай light brown OY-27207 - 13.8 mg (a gipromelloza of 2910 - 62.5%, titanium dioxide - 21.25%, a macrogoal of 400 - 6.25%, dye a sunset yellow - 9%, indigo carmine - 1%).

Tablets of the prolonged action, film coated red color, a kapsulovidny form, biconvex, with an engraving of "GS" on one party and "5CC" - on another.

Active ingredient: a ropinirola a hydrochloride of 9.12 mg that corresponds to the maintenance of a ropinirol of 8 mg

Excipients: upper barrier layer: a gipromelloza of 2208 - 62.83 mg, glyceryl дибеганат - 35 mg, Mannitolum - 33.04 mg, K29-32 povidone - 7 mg, magnesium stearate - 1.4 mg, silicon dioxide colloid - 0.56 mg, gland (III) oxide (yellow) - 0.17 mg; an active layer - a gipromelloza of 2208 - 61.5 mg, lactoses monohydrate - 39.48 mg, a karmelloza of sodium - 15 mg, the castor oil hydrogenated - 15 mg, maltodextrin - 7.5 mg, magnesium stearate - 1.5 mg, silicon dioxide colloid - 0.9 mg; lower barrier layer: a gipromelloza of 2208 - 76.29 mg, glyceryl дибеганат - 42.5 mg, Mannitolum - 40.12 mg, K29-32 povidone - 8.5 mg, magnesium stearate - 1.7 mg, silicon dioxide colloid - 0.68 mg, gland (III) oxide (yellow) - 0.21 mg.

Structure of a film cover: dye опадрай red 03B25227 - 13.8 mg (a gipromelloza of 2910 - 62.5%, titanium dioxide - 24.19%, a macrogoal of 400 - 6.25%, iron (II) oxide (red) - 6.14%, gland (III) oxide (black) - 0.89%, gland (III) oxide (yellow) - 0.03%).

Pharmacological properties:

Protivoparkinsonichesky drug, highly the selection neergolinovy agonist of dopamine D2-, D3 receptors which possess peripheral and central action.

Drug does not affect the collapsing presynaptic dopaminergic neurons of black substance and works directly as the synthetic neurotransmitter. Thus, ропинирол reduces degree of a hypodynamia, rigidity and a tremor which are parkinsonism symptoms.

Ropinirol compensates deficit of a dopamine in systems of black substance and a striate body by means of stimulation of dopamine receptors in a striate body.

Ropinirol strengthens effects of a levodopa, including the control of frequency of a phenomenon of inclusion/switching off and effect of "the end of a dose" connected with long therapy by levodopa drugs and allows to reduce a daily dose of a levodopa.

Ropinirol has effect at the level of a hypothalamus and a hypophysis, inhibiting prolactin secretion.

Pharmacokinetics. The pharmacokinetics of a ropinirol is similar at healthy people, patients to a disease of Parkinson and patients to a syndrome of uneasy legs and differs depending on a dosage form.

Absorption

After intake bioavailability of a ropinirol low also makes about 50% (36-57%). After intake of a ropinirol in tablets of the slowed-down release its concentration in plasma increases slowly, the average time of Tmax makes 6 h. Patients with Parkinson's disease after intake have a ropinirola in a dose of 12 mg of 1 times / in combination with the food rich with fats, in an equilibrium state increase in system exposure of a ropinirol was observed, at the same time increase in AUC and Cmax by 20% and 44% respectively was noted, Tmax was extended on 3 h. However in clinical trials of efficiency and safety ропинирол was accepted regardless of meal.

Increase in duration of systemic action of a ropinirol (Cmax and AUC) is approximately proportional to increase in a dose.

Distribution

Linkng with proteins of a blood plasma low (10-40%). Thanks to high lipophilicity ропинирол it is characterized by big Vd (about 7 l/kg).

Metabolism

Ropinirol is mainly metabolized by CYP1A2 isoenzyme.

Removal

T1/2 of a ropinirol from a system blood-groove averages about 6 h. The metabolite of a ropinirol is generally removed by kidneys. There are no differences in removal of a ropinirol after a single dose of a dose inside or at regular use.

Pharmacokinetics in special clinical cases

The clearance of a ropinirol after intake decreases approximately by 15% at patients of advanced age (65 years and are more senior) in comparison with younger patients. Dose adjustment is not required from this category of patients.

Pharmacokinetic indicators do not change at patients with a renal failure of easy and average degree and Parkinson's disease. At the patients with a final stage of a renal failure who are on a constant hemodialysis, the clearance of a ropinirol at intake decreases approximately by 30%.

Indications to use:

Parkinson's disease:

— monotherapy of early stages of a disease at the patients needing dopaminergic therapy to delay purpose of drugs of a levodopa;

— as a part of a combination therapy at the patients receiving levodopa drugs for the purpose of increase in efficiency of a levodopa, including control of fluctuation ("inclusion switching off") and effect of "the end of a dose" against the background of chronic therapy of a levodopa, and also for decrease in a daily dose of a levodopa.

Route of administration and doses:

Drug is appointed in 1 times / at the same time regardless of meal. A pill is taken entirely, without chewing, without breaking.

Individual selection of a dose according to efficiency and portability of drug is recommended.

The dose decline is recommended if the patient tests drowsiness at any stage of selection of a dose. At development of other undesirable reactions it is necessary to lower a drug dose with the subsequent gradual increase in a dose.

It must be kept in mind need of titration of a dose at the admission of a dose (one and more).

Monotherapy

Initiation of treatment

The recommended initial dose of drug Rekvip of Modutab® makes 2 mg of 1 times / within one week. Afterwards the dose is increased by 2 bucketed mg not less than 1 week to 8 mg /

Week 1 2 3 4
Daily dose (mg) 2 4 6 8

Maintenance dose

If after selection of a dose the therapeutic effect is insufficiently expressed or is unstable, it is possible to continue increase in a daily dose of drug by 4 bucketed mg 1-2 weeks (before achievement of necessary therapeutic effect). The dose can be changed depending on therapeutic effect and is increased to the maximum dose of 24 mg of 1 times /

Combination therapy

When using drug Rekvip Modutab® in the doses used at monotherapy in a combination with levodopa drugs, a dose of a levodopa it is possible to reduce gradually (depending on clinical effect). In clinical trials at the patients who are at the same time receiving Rekvip Modutab® in tablets with the slowed-down release, the levodopa dose was gradually lowered approximately by 30%. Patients with the progressing form have diseases, Modutab® accepting Rekvip in a combination with levodopa drugs, during titration of a dose of a ropinirol there can be dyskinesia. The dose decline of drugs of a levodopa can lead to reduction of this symptomatology.

Therapy cancellation. Rekvip Modutab® (as well as other dopaminergic drugs) should be cancelled, gradually reducing a daily dose within not less than 1 week. If treatment was interrupted for 1 day and more, then when resuming therapy it is necessary to consider a question of need of titration of a dose.

Despite possible decrease in clearance of drug at patients at the age of 65 years is also more senior, titration of a dose of a ropinirol at this category of patients is carried out as usual.

At patients with a renal failure easy and moderate severity (KK of 30-50 ml/min.) the clearance of a ropinirol does not change, dose adjustment of a ropinirol is not required.

For the patients with a final stage of a renal failure who are on a hemodialysis, the recommended initial dose of a ropinirol makes 2 mg of 1 times / the Subsequent increase in a dose has to be based on assessment of portability and efficiency. The maximum daily dose at the patients who are on a constant hemodialysis makes 18 mg. Introduction of maintenance doses after carrying out a hemodialysis is not required.

Features of use:

Patients should be warned about the possible development of drowsiness or episodes of sudden backfilling which sometimes are not preceded by drowsiness. In case of such reactions it is necessary to consider the possibility of cancellation of therapy.

Monitoring of the ABP because of a possibility of development of orthostatic hypotension is recommended.

At the patients accepting dopaminergic drugs, including ропинирол it was reported about frustration of an inclination, including compulsive behavior, such as a morbid attraction to gamblings and hyper sexuality. According to literature, similar side effects of therapy were noted at the patients with Parkinson's disease receiving high doses of dopaminergic drugs; other risk factors can be compulsive behavior in the anamnesis or the combined use of several dopaminergic drugs. In this case it is necessary to consider the possibility of a dose decline or cancellation of therapy.

The paradoxical aggravation of symptoms at a syndrome of uneasy legs was noted at therapy ropiniroly (earlier beginning, the increased intensity of manifestations, or progressing of symptoms with involvement of earlier not affected extremities), or a ricochet syndrome early morning hours (a recurrence of symptoms early morning hours). At emergence of these symptoms it is necessary to reconsider treatment tactics ropiniroly, to specify a dose up to possible drug withdrawal.

Influence on ability to driving of motor transport and to control of mechanisms

Patients should be warned about possible undesirable reactions during therapy ropiniroly.

Patients have to be informed that there are very exceptional cases of episodes of sudden backfilling without any previous or strong indications of day drowsiness and dizziness cases (sometimes expressed). At development of day drowsiness or episodes of backfilling during the day that demands active intervention, the patient needs to be warned about need to refuse driving of the vehicles and other types of activity demanding high concentration of attention and speed of psychomotor reactions.

Side effects:

Determination of frequency of side reactions: very often (≥1/10); often (≥1/100, <1/10); sometimes (≥1/1000, <1/100); seldom (≥1/10 000, <1/1000); very seldom (<1/10 000, including separate cases).

Data of clinical trials at patients with Parkinson's disease

Frequency      Use in quality             Use in structure
                  monotherapies               of a combination therapy
                            From TsNS
very often        drowsiness                 diskineziya1
often        hallucinations,   hallucination dizziness, confusion of consciousness,
                (up to strong)       drowsiness, dizziness (up to strong)
                       From cardiovascular system
                                       often orthostatic hypotension, decrease in the ABP
sometimes     orthostatic hypotension,
                   decrease in the ABP
                        From the alimentary system
very often            nausea
often        abdominal pains, dyspepsia,        nausea, lock
                  vomiting, lock
                           General reactions
          often peripheral hypostases          peripheral hypostases
               (including hypostases of legs)

1 Patients with the progressing form have diseases, accepting Rekvip Modutab, in a combination with levodopa drugs, during titration of a dose development of a lack of coordination of movements is possible. It was shown that cancellation of drugs of a levodopa can lead to reduction of this symptomatology.

Post-marketing data

From TsNS and peripheral nervous system: sometimes - psychotic states (including a delirium and nonsense), disorders of perception (including illusions, excepting hallucinations), increase in impulsiveness, increase in a libido, including hyper sexuality, a morbid attraction to gamblings; very seldom - the expressed drowsiness, episodes of sudden backfilling (as well as in case of use of other dopaminergic means, these symptoms very seldom were registered at patients with Parkinson's disease). At a dose decline or drug withdrawals all symptoms disappeared. The accompanying sedative drugs were in most cases used.

From cardiovascular system: often - orthostatic hypotension, decrease in the ABP.

Allergic reactions: very seldom - a small tortoiseshell, a Quincke's disease, rash, an itch.

Interaction with other medicines:

Typical neuroleptics and other dopamine antagonists of the central action, such as Sulpiridum or Metoclopramidum, are capable to reduce efficiency of a ropinirol (it is necessary to avoid co-administration).

Pharmacokinetic interaction between ropiniroly and a levodopa or domperidony which would demand correction of doses of these drugs is noted.

Ropinirol does not interact with other drugs which are used often for treatment of a disease of Parkinson.

At the patients with Parkinson's disease accepting at the same time digoxin interaction of digoxin with ropiniroly which would demand correction of doses was not revealed.

Ropinirol, is generally metabolized by CYP1A2 isoenzyme. Pharmacokinetic researches at patients with Parkinson's disease showed that ciprofloxacin increases Cmax and AUC of a ropinirol approximately by 60% and 84% respectively. In this regard, at the patients receiving ропинирол its dose has to be corrected at appointment and cancellation of the drugs inhibiting CYP1A2 isoenzyme, for example, of ciprofloxacin, an enoksatsina or a fluvoksamina.

The pharmacokinetic research of medicinal interaction at patients with Parkinson's disease between ropiniroly and the theophylline which is CYP1A2 isoenzyme substrate showed that the pharmacokinetics of drugs does not change. At simultaneous use of a ropinirol with other substrates of an isoenzyme CYP1A2 the pharmacokinetics of a ropinirol does not change.

Increase in concentration of a ropinirol in plasma was observed at the patients receiving estrogen in high doses. At the patients receiving replacement hormonal therapy prior to treatment ropiniroly treatment ropiniroly can be begun according to the usual scheme. However in case of the termination of replacement hormonal therapy or its beginning during therapy ropiniroly dose adjustment can be required.

There is no information on a possibility of interaction of a ropinirol and ethanol. As well as in a case with other drugs of the central action, patients have to be warned about need to refrain from alcohol intake during treatment ropiniroly.

It is known that nicotine induces CYP1A2 isoenzyme therefore if the patient begins or stops smoking during treatment ropiniroly, correction of its dose can be required.

Contraindications:

— acute psychosis;

— abnormal liver functions;

— heavy renal failures (KK less than 30 ml/min.) which does not carry out a regular hemodialysis;

— rare hereditary diseases: lactose intolerance, lactose intolerance, disturbances of absorption of glucose or galactose;

— pregnancy;

— lactation;

— children's and teenage age up to 18 years;

— hypersensitivity to drug components.

With care it is necessary to use drug at patients with heavy cardiovascular insufficiency. Ropinirol patients can appoint with psychotic frustration in the anamnesis only in those cases if the expected advantage of its use exceeds potential risk.

 

Use of drug REKVIP MODUTAB® at pregnancy and feeding by a breast

Use at pregnancy and in the period of a lactation (breastfeeding) is contraindicated.

Use at abnormal liver functions

Contraindication: abnormal liver functions.

Use at renal failures

At patients with a renal failure easy and moderate severity (KK of 30-50 ml/min.) the clearance of a ropinirol does not change, dose adjustment of a ropinirol is not required.

For the patients with a final stage of a renal failure who are on a hemodialysis, the rekomeduyemy initial dose of a ropinirol makes 2 mg of 1 times / the Subsequent increase in a dose has to snovyvatsya on assessment of portability and efficiency. The maximum daily dose at the patients who are on a constant hemodialysis makes 18 mg. Introduction of maintenance doses after carrying out a hemodialysis is not required.

 

Use for elderly patients

Despite possible decrease in clearance of drug at patients at the age of 65 years is also more senior, titration of a dose of a ropinirol at this category of patients is carried out as usual.

 

Use for children

Contraindicated: children's and teenage age up to 18 years.

Overdose:

Symptoms: are generally caused by dopaminergic action - nausea, vomiting, dizziness, drowsiness.

Treatment: use of antagonists of a dopamine, such as typical neuroleptics and Metoclopramidum.

Storage conditions:

Drug should be stored in the place, unavailable to children, in original packaging, at a temperature not above 25 °C. A period of validity for tablets of 2 mg - 2 years, for tablets of 4 mg and 8 mg - 3 years.

Issue conditions:

According to the recipe

Packaging:

• tablets пролонгир. actions, film cover, 2 mg: 28, 42 or 84

• tablets пролонгир. actions, film cover, 4 mg: 28 or 84

• tablets пролонгир. actions, film cover, 8 mg: 28 or 84