Rekvip Modutab, 8 mg 28 pcs

Requip Modutab is an antiparkinsonian drug, a highly selective non-ergoline agonist of dopamine D 2 -, D 3 -receptors, which has peripheral and central action.

The drug does not act on disrupting presynaptic dopaminergic black matter neurons and acts directly as a synthetic neurotransmitter. Thus, ropinirole reduces the degree of hypodynamia, rigidity and tremor, which are symptoms of parkinsonism.

Ropinirol compensates for dopamine deficits in the black matter and striatum systems by stimulating dopamine receptors in the striatum.

Ropinirole enhances the effects of levodopa, including the control of on/off frequency phenomenon and “end-of-dose” effects associated with long-term levodopa drug therapy, and allows a reduction in the daily levodopa dose. Ropinirole acts at the hypothalamic and pituitary levels by inhibiting prolactin secretion.

Pharmacokinetics

The pharmacokinetics of ropinirole are similar in healthy subjects, Parkinson’s patients and patients with restless legs syndrome and differ depending on the dosage form.

Intake.

The bioavailability of ropinirole after oral administration is low and is approximately 50% (36%-57%). After oral administration of ropinirole in slow release tablets its concentration in plasma increases slowly, the average time of reaching the maximum concentration (Tmax) is 6 hours. In equilibrium patients with Parkinson’s disease after oral administration of 12 mg ropinirole once daily in combination with fat-rich food, an increase in systemic ropinirole exposure was observed, with the area under “concentration-time” curve (AUC) and maximum concentration (Cmax) increasing by 20% and 44% respectively, Tmax was prolonged by 3 hours. However, in clinical studies of efficacy and safety ropinirole was taken regardless of food intake.

Binding to plasma proteins and distribution. Binding to plasma proteins is low (10-40%). Due to high lipophilicity ropinirole is characterized by high volume of distribution (approximately 7 l/kg).

Metabolism. Ropinirole is mainly metabolized by CYP1A2 isoenzyme.

The metabolite of ropinirole is mainly excreted by the kidneys.

Evacuation. On average, the elimination half-life of ropinirole from the systemic bloodstream is about 6 hours. The increase in the duration of systemic action of ropinirole (Cmax and AUC) is approximately proportional to the increase in dose. There is no difference in excretion 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 to younger patients. No dose adjustment is required in this category of patients.

Patients with impaired renal function

Pharmacokinetic parameters are not changed in patients with mild to moderate renal impairment and Parkinson’s disease.
In patients with end-stage renal failure who are on permanent hemodialysis, oral ropinirole clearance is reduced by approximately 30%.

Indications

Parkinson’s disease:

Active ingredient

Composition

Active ingredient:

rpinirole hydrochloride;

Associates:

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.

How to take, the dosage

Adults

Intravenously.

Requip Modutab should be taken once daily at the same time, regardless of meals. The tablets should be taken whole, without chewing or crushing.

The need for dose titration should be considered when missing a dose (one or more).

Dose reduction is recommended if the patient experiences drowsiness at any stage of dose titration.
If other adverse reactions develop, the dose of the drug should be reduced followed by a gradual increase in the dose.
Individual adjustment of the dose according to the effectiveness and tolerability of the drug is recommended.

Monotherapy

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

The maintenance dose
If after adjusting the dose the therapeutic effect is not sufficiently pronounced or is not stable, the daily dose of the drug can be increased further by 4 mg at 1-2 week intervals (until the desired therapeutic effect is achieved).

The dose can be changed depending on the therapeutic effect and is increased up to maximum dose of 24 mg once a day.

Interaction

Typical neuroleptics and other centrally acting dopamine antagonists, such as sulpiride or metoclopramide, can decrease the effectiveness of ropinirole (concomitant administration should be avoided).

There are no pharmacokinetic interactions between ropinirole and levodopa or domperidone that would require dose adjustments of these drugs. Ropinirole does not interact with other drugs that are commonly used to treat Parkinson’s disease. In Parkinson’s patients taking digoxin at the same time, no interaction between digoxin and ropinirole has been found that would require dose adjustments.

Ropinirol is primarily metabolized by the CYP1A2 isoenzyme. Pharmacokinetic studies in patients with Parkinson’s disease have shown that ciprofloxacin increases the C max and AUC of ropinirole by approximately 60% and 84%, respectively. Therefore, in patients receiving ropinirole, its dose should be adjusted when prescribing and withdrawing drugs that inhibit CYP1A2 isoenzyme, such as ciprofloxacin, enoxacin or fluvoxamine.

Pharmacokinetic studies of drug interactions in patients with Parkinson’s disease between ropinirole and theophylline, a substrate of the CYP1A2 isoenzyme, have shown that the pharmacokinetics of the drugs are not altered. When using ropinirole concomitantly with other CYP1A2 isoenzyme substrates, the pharmacokinetics of ropinirole is not altered.

Elevated plasma concentrations of ropinirole have been observed in patients receiving high-dose estrogens. In patients receiving hormone replacement therapy before treatment with ropinirole, treatment with ropinirole can be started according to the usual scheme. However, in case of discontinuation of hormone replacement therapy or its initiation during therapy with ropinirole, a dose adjustment may be required. There is no information about the possibility of interaction between ropinirole and ethanol.

As with other centrally acting drugs, patients should be warned to refrain from taking alcohol during treatment with ropinirole. Nicotine is known to induce the CYP1A2 isoenzyme, so a dose adjustment may be required if a patient starts or stops smoking during treatment with ropinirole.

Special Instructions

Patients should be warned about the possible development of somnolence or episodes of sudden falling asleep, sometimes not preceded by somnolence. If these reactions occur, discontinuation of therapy should be considered.

PHR monitoring is recommended because of the possibility of orthostatic hypotension. In patients taking dopaminergic drugs, including ropinirole, craving disorder including compulsive behavior such as pathological craving for gambling and hypersexuality have been reported.

The literature suggests that these adverse effects of therapy have been reported in patients with Parkinson’s disease receiving high doses of dopaminergic drugs; other risk factors may include a history of compulsive behavior or the combined use of multiple dopaminergic drugs. Dose reduction or withdrawal of therapy should be considered in this case.

Paradoxical worsening of restless legs syndrome has been noted with therapy with ropinirole (earlier onset, increased intensity of manifestations, or progression of symptoms involving previously unaffected extremities), or ricochet syndrome in the early morning hours (relapse of symptoms in the early morning hours).

If these symptoms occur, the therapy with ropinirole should be reconsidered and the dose should be adjusted, up to and including possible withdrawal of the drug.

Contraindications

Side effects

CNS disorders: drowsiness, dyskinesia; hallucinations, dizziness (up to severe); confusion, drowsiness, dizziness (up to severe);

Cardiovascular disorders: orthostatic hypotension, decreased BP, orthostatic hypotension, decreased BP;

Digestive system disorders: nausea, abdominal pain, dyspepsia, vomiting, constipation;

General reactions: peripheral edema (including leg edema);

CNS and peripheral nervous system disorders: Psychotic states (including delirium and delirium), perceptual disturbances (including illusions, excluding hallucinations), increased impulsivity, increased libido, including hypersexuality, pathological cravings for gambling; marked somnolence, episodes of sudden falling asleep (as with other dopaminergic agents, these symptoms have very rarely been reported in patients with Parkinson’s disease ). When the dose was reduced or the drug was withdrawn, all symptoms disappeared. In most cases, concomitant sedation was used.

Cardiovascular system: orthostatic hypotension, decreased BP.

Allergic reactions: urticaria, angioedema, rash, itching.

Overdose

Symptoms: mainly the symptoms of ropinirole overdose are related to dopaminergic effects (nausea, vomiting, dizziness, drowsiness).

Treatment: these symptoms can be corrected with appropriate treatment with dopamine antagonists such as typical neuroleptics and metoclopramide.

Pregnancy use

Pregnancy is possible if the expected effect of therapy is greater than the potential risk to the fetus.

The FDA fetal category is C.

Ropinirol inhibits prolactin secretion in humans and can potentially inhibit lactation. Animal studies have shown that ropinirole and/or its metabolites are excreted into the milk of lactating rats. It is not known whether ropinirole is excreted into human breast milk.

Because many drugs are excreted in the milk of women and there may be serious adverse effects of ropinirole on the infant, a decision should be made either to stop breastfeeding or to stop taking ropinirole (given the degree of maternal need for the drug).

Similarities