Active ingredients: Ropinirole (Ropinirole hydrochloride)
Requip 0.25 mg film-coated tablets
Requip 0.5 mg film-coated tablets
Requip 1 mg film-coated tablets
Requip 2 mg film-coated tablets
Requip 5 mg film-coated tablets
Requip package leaflets are available for the packs: - Requip 0.25 mg film-coated tablets, Requip 0.5 mg film-coated tablets, Requip 1 mg film-coated tablets, Requip 2 mg film-coated tablets, Requip 5 mg film-coated tablets
- REQUIP 2 mg prolonged-release tablets, REQUIP 4 mg prolonged-release tablets, REQUIP 8 mg prolonged-release tablets
Indications Why is Requip used? What is it for?
The active substance in Requip is ropinirole, which belongs to a group of medicines called dopamine agonists. Dopamine agonists act on the brain in a similar way to a natural substance called dopamine.
Requip is used to treat Parkinson's disease. People with Parkinson's disease have low dopamine levels in parts of the brain. Ropinirole has effects similar to those of natural dopamine, thus helping to reduce the symptoms of Parkinson's disease.
Contraindications When Requip should not be used
Do not take Requip
- if you are allergic (hypersensitive) to the active substance, ropinirole, or to any of the other ingredients of this medicine (listed in sections 4 and 6).
- if you have severe kidney disease
- if you have liver disease
Tell your doctor if you think any of these apply to you.
Precautions for use What you need to know before taking Requip
Talk to your doctor or pharmacist before taking Requip:
- if you are pregnant or think you are
- if you are breast-feeding
- if you are under 18 years of age
- if you have severe heart disease
- if you have a severe mental health problem
- if you have experienced any unusual stimuli and / or behavior (such as excessive gambling or excessive sexual behavior).
- if you are intolerant to some sugars (such as lactose)
Tell your doctor if you or your family member / caregiver notice that you are developing urges or wishes to behave in a way that is unusual for you and cannot resist the urge, desire or temptation to do certain activities that could be harmful to yourself or others. These are called impulse control disorders and can include behaviors such as gambling addiction, excessive eating or spending, abnormally high sex drive or increased thinking or sexual sensations Your doctor may need to adjust or stop your treatment.
Tell your doctor if you think any of these apply to you. Your doctor may decide that Requip is not suitable for you, or that further checks are needed while you are taking it.
During treatment with Requip
Tell your doctor if you or your family members notice that you are developing any unusual behavior (such as an unusual urge to gamble or an increase in sexual urge and / or behavior) while you are taking Requip. Your doctor may find it necessary to change your dose or stop taking.
Driving and using machines
Requip can cause drowsiness. It can cause extreme drowsiness and sometimes makes you fall asleep suddenly without warning symptoms. If you suffer from these symptoms: do not drive vehicles, do not operate machinery and do not put yourself in situations where feeling sleepy or suddenly falling asleep may put you (or other people) ) at risk of serious injury or death Do not participate in such activities until you no longer suffer from them.
Talk to your doctor if this causes you problems. Smoking habits and Requip Tell your doctor if you start smoking or if you stop smoking while taking Requip. Your doctor may find it necessary to change your dosage.
Interactions Which drugs or foods can modify the effect of Requip
Other medicines and Requip
Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines, including herbal products or medicines without a prescription. Remember to tell your doctor or pharmacist if you are starting to take a new medicine while you are taking Requip.
Some medicines can affect the way Requip works, or make side effects more likely. Requip can also affect the way some other medicines work.
These medicines include:
- the anti-depressant fluvoxamine
- medicines to treat other mental health problems, for example sulpiride
- hormone replacement therapy (HRT)
- metoclopramide, used to treat nausea and heartburn
- the antibiotics ciprofloxacin or enoxacin
- any other medicines for the treatment of Parkinson's disease
Tell your doctor if you are taking, or have recently taken, any of these medicines.
You will need further blood tests if you are taking these medicines with Requip:
- vitamin K antagonists (used to reduce blood clotting) such as warfarin (Coumadin).
Requip with food and drink
If you take Requip with food it can reduce the likelihood of feeling sick or vomiting. If possible, it is therefore preferable to take Requip with food.
Warnings It is important to know that:
Pregnancy and breastfeeding
Requip is not recommended if you are pregnant unless your doctor considers that the benefit of taking Requip outweighs the risk to the unborn baby. Requip is not recommended if you are breastfeeding, as it may affect about milk production. Tell your doctor immediately if you are pregnant, think you may be pregnant or plan to become pregnant. Your doctor will advise you if you are breastfeeding or intend to breastfeed. Your doctor may advise you to stop. the assumption of Requip.
Requip tablets contain a small amount of a sugar called lactose. If your doctor has diagnosed you with intolerance to some sugars, contact your doctor before taking Requip.
Dose, Method and Time of Administration How to use Requip: Posology
Always take this medicine exactly as your doctor or pharmacist has told you. If in doubt, consult your doctor or pharmacist.
Requip alone may be prescribed to treat the symptoms of Parkinson's disease. It may also be prescribed to you together with another medicine called L-dopa (also called levodopa). Do not give Requip to children. Requip is not normally prescribed to people under the age of 18.
How much Requip should you take?
It may take some time to find the optimal dose of Requip for you. The usual starting dose is 0.25 mg of ropinirole three times a day for the first week. Thereafter, your doctor will increase the dose every week for the next three weeks. After that, your doctor will gradually increase the dose until the optimal dose for you is reached. The usual dose is 1 to 3 mg three times a day (i.e. a total daily dose of 3 to 9 mg). If your Parkinson's disease symptoms do not improve sufficiently, your doctor may decide to increase the dose slightly gradually. Some patients take up to 8 mg of Requip three times a day (in total, 24 mg a day). If you are also taking other medicines to treat Parkinson's disease, your doctor may advise you to gradually reduce the dosage of the other medicines. If you are taking L-dopa you may have some uncontrollable movements (dyskinesia) when you start taking Requip. If this happens, please tell your doctor, as your doctor may need to adjust the dose of the medicines you are taking.
Do not take more Requip than recommended by your doctor. It may take a few weeks for Requip to work.
Taking the Requip dose
Take Requip three times a day.
The Requip tablet should be swallowed whole, with a glass of water. It is preferable to take Requip with food, in this way the onset of nausea is less likely.
Overdose What to do if you have taken an overdose of Requip
If you take more Requip than you should
Contact your doctor or pharmacist immediately. If possible, show them the Requip pack. Those who take more than necessary Requip may experience: nausea, vomiting, dizziness, drowsiness, mental or physical fatigue, fainting, hallucinations.
If you forget to take Requip
Do not take additional tablets or a double dose to make up for a forgotten dose. Just take your next dose at the usual time.
If you have forgotten to take Requip for a day or more, ask your doctor for advice on how to start treatment again.
Do not stop taking Requip without your doctor's advice
Take Requip for as long as your doctor recommends it. Don't stop unless your doctor tells you to. If you stop taking Requip abruptly, your Parkinson's disease symptoms can get worse quickly.
If you need to stop taking Requip, your doctor will reduce your dose gradually.
If you have any further questions on the use of this medicine, ask your doctor or pharmacist.
Side Effects What are the side effects of Requip
Like all medicines, this medicine can cause side effects, although not everybody gets them.Side effects with Requip are more likely to occur when treatment is started or when the dose is increased. Side effects are usually mild and may subside after you have taken the medicine for a short time. If you are concerned about side effects , talk to your doctor.
Very common side effects
These may affect more than 1 in 10 people taking Requip:
- fainting
- drowsiness
- nausea
Common side effects
These may affect up to 1 in 10 people who take Requip:
- hallucinations ("seeing" things that don't really exist)
- He retched
- dizziness
- stomach ache
- abdominal pain
- swelling of the legs, feet or hands
Uncommon side effects
These may affect up to 1 in 100 people who take Requip:
- dizziness or fainting, especially when standing up from a sitting or lying position (caused by a drop in blood pressure)
- extreme sleepiness during the day
- falling asleep suddenly without feeling sleepy first (sudden sleep episodes)
- mental problems, such as deep confusion, delirium (irrational ideas) and paranoia (suspicious irrational attitude)
Very rare side effects
A very small number of people taking Requip (up to 1 in 10,000) have had changes in liver function, which have been seen in blood tests.
Some patients may have the following side effects (frequency not known)
- allergic reactions, such as swollen, red and itchy skin (hives), swelling of the face, lips, mouth, tongue or throat, which may cause difficulty in swallowing and breathing, rash or severe itching (see section 2)
- aggression.
You may experience the following side effects:
inability to resist the urge, desire or temptation to take actions that could be harmful to you or others, which may include:
- strong impulse to gamble excessively despite serious personal or family consequences
- altered or increased sexual interest and behavior of significant concern to you or to others, for example increased sexual desire
- uncontrollable excessive purchases or spending
- overeating (eating large amounts of food in a short period of time) or compulsive eating (taking in more food than needed to satisfy hunger)
Tell your doctor if you experience any of these behaviors; how to manage or reduce symptoms will be discussed.
If you take Requip together with L-dopa
Those who take Requip together with L-dopa may have other side effects over time:
- uncontrollable movements (dyskinesia) are a very common side effect. If you are taking L-dopa you may have some uncontrollable movements (dyskinesia) when you start taking Requip. If this happens, please tell your doctor, as your doctor may need to adjust the dose of the medicines you are taking.
- feeling confused is a very common side effect
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at: www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label / blister and carton.
The expiry date refers to the last day of that month.
Do not store above 25 ° C.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Composition and pharmaceutical form
What Requip
The active ingredient of Requip is ropinirole. One film-coated tablet contains 0.25; 0.5; 1; 2 or 5 mg of ropinirole (as hydrochloride).
The other ingredients are:
- tablet core: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium stearate
- coating film:
0.25 mg tablets: hypromellose, macrogol 400, titanium dioxide (E 171), polysorbate 80 (E 433).
0.5 mg tablets: hypromellose, macrogol 400, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172), indigo carmine lake (E 132).
1 mg tablets: hypromellose, macrogol 400, titanium dioxide (E 171), yellow iron oxide (E 172), indigo carmine lake (E 132).
2 mg tablets: hypromellose, macrogol 400, titanium dioxide (E 171), yellow iron oxide (E 172), red iron oxide (E 172).
5 mg tablets: hypromellose, macrogol 400, titanium dioxide (E 171), indigo carmine lake (E 132), polysorbate 80 (E 433).
Description of the appearance of Requip and contents of the package
Requip is supplied as pentagonal shaped, film-coated tablets, debossed with "SB" on one side
Requip 0.25 mg: white tablets with "4890" on the other side.
Requip 0.5 mg: yellow tablets with "4891" debossed on the other side.
Requip 1 mg: green tablets with "4892" on the other side.
Requip 2 mg: pink tablets with "4893" on the other side.
Requip 5 mg: blue tablets with "4894" on the other side.
The 0.25 tablets are supplied in blisters of 21, 126 or 210 tablets.
The 0.5 mg tablets are supplied in blisters of 21 tablets.
The 1 mg, 2 mg and 5 mg tablets are supplied in blisters of 21 or 84 tablets.
All strengths are supplied in bottles containing 84 tablets.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
REQUIP TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Requip 0.25 mg film-coated tablets:
Each film-coated tablet contains 0.25 mg of ropinirole as ropinirole hydrochloride.
Excipients: 45.3 mg of lactose
Requip 0.5 mg film-coated tablets:
Each film-coated tablet contains 0.5 mg of ropinirole as ropinirole hydrochloride.
Excipients: 45.0 mg of lactose
Requip 1 mg film-coated tablets:
Each film-coated tablet contains 1 mg of ropinirole as ropinirole hydrochloride.
Excipients: 44.9 mg of lactose
Requip 2 mg film-coated tablets:
Each film-coated tablet contains 2 mg of ropinirole as ropinirole hydrochloride.
Excipients: 44.6 mg of lactose
Requip 5 mg film-coated tablets:
Each film-coated tablet contains 5 mg of ropinirole as ropinirole hydrochloride.
Excipients: 43.7 mg of lactose
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet.
Requip 0.25 mg film-coated tablets:
white, pentagonal in shape, embossed on one side with "SB" and "4890" on the other side.
Requip 0.5 mg film-coated tablets:
yellow, pentagonal in shape, embossed on one side with "SB" and "4891" on the other side.
Requip 1 mg film-coated tablets:
green, pentagonal in shape, embossed on one side with "SB" and "4892" on the other side.
Requip 2 mg film-coated tablets:
pink, pentagonal in shape, imprinted on one side with "SB" and "4893" on the other side.
Requip 5 mg film-coated tablets:
blue, pentagonal in shape, imprinted on one side with "SB" and "4894" on the other side.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Treatment of Parkinson's disease in the following clinical situations:
• on its own as initial treatment, in order to postpone the initiation of levodopa therapy
• in association with levodopa treatment, during the course of the disease, when the effect of levodopa therapy fades or becomes unstable, thereby causing fluctuations in the "therapeutic effect (" end of dose deterioration "or" end-of-dose fluctuations " on-off ").
04.2 Posology and method of administration
Oral use.
Adults
Individual dose titration is recommended as a function of efficacy and tolerability.
Requip should be taken three times a day, preferably in conjunction with meals to improve gastrointestinal tolerability.
Start of treatment
The starting dose of ropinirole should be 0.25 mg three times a day for 1 week. Thereafter, the dose of ropinirole can be increased by 0.25 mg for each of the three daily administrations, according to the following schedule:
Continuation of the treatment
At the end of the initial titration, the further dose increase may be between 0.5 mg and 1 mg of ropinirole for each of the three daily administrations (from 1.5 to 3 mg / day), on a weekly basis.
Therapeutic response can be observed at a dose ranging from 3 to 9 mg / day of ropinirole. If sufficient symptom control is not achieved, or is not maintained after the initial titration described above, the dose of ropinirole can be progressively increased up to 24 mg / day.
Dosages of ropinirole above 24 mg / day have not been studied.
If treatment is interrupted for one or more days, consideration should be given to restarting treatment with dose titration (see above).
If ropinirole is given in combination with levodopa, the dose of levodopa may be gradually decreased based on symptomatic response. In clinical trials the dose of levodopa was gradually reduced to a reduction of approximately 20% in patients treated with Requip as add-on therapy. In patients with advanced Parkinson's disease receiving ropinirole in combination with levodopa, dyskinesia may occur during the initial titration of ropinirole. In clinical trials it has been shown that a reduction in the dose of levodopa may improve dyskinesia ( see section 4.8).
When switching from treatment with another dopamine agonist to ropinirole, discontinuation of the previous treatment should be done following the schedule for that product, before switching to ropinirole administration.
As with other dopamine agonists, ropinirole treatment should be withdrawn gradually, reducing the number of daily administrations over a week.
Children and adolescents
The use of Requip is not recommended in children below 18 years of age due to a lack of efficacy and safety data.
Elderly patients
In patients 65 years of age and older, the clearance of ropinirole is reduced by about 15%. Although no dosage adjustment is required, the dose of ropinirole should be individually titrated, with careful monitoring of tolerability, until optimal clinical response is achieved.
Patients with renal impairment
In patients with mild to moderate renal impairment (clearance creatinine between 30 and 50 ml / min) no changes were observed clearance of ropinirole; this indicates that no dosage adjustment is required in this patient population.
A study on the use of ropinirole in patients with end stage renal disease (hemodialysis patients) showed that the following dosage regimen adjustment is required in these patients: the starting dose of Requip film-coated tablets should be 0.25 3 mg three times a day. Further dose increases should be based on tolerability and efficacy. In patients receiving regular hemodialysis, the maximum recommended dose of Requip film-coated tablets is 18 mg per day. No additional doses are required after hemodialysis. (see section 5.2).
The use of ropinirole in patients with severe renal insufficiency (clearance creatinine less than 30 ml / min) without regular hemodialysis has not been studied.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Severe renal impairment (clearance of creatinine
Hepatic impairment.
04.4 Special warnings and appropriate precautions for use
Ropinirole has been associated with somnolence and episodes of sudden sleep attacks, particularly in patients with Parkinson's disease. Sudden sleep attacks during daily activities have been reported uncommonly, in some cases unknowingly or without warning signs. Patients should be advised of this and advised to exercise caution while driving or operating machinery during treatment with ropinirole. Patients who have experienced somnolence and / or episodes of sudden sleep onset should refrain from driving or operating machinery. during treatment with ropinirole.
Dosage reduction or discontinuation of therapy should be considered.
Patients with major psychiatric or psychotic disorders, or with a history of such disorders, should be treated with dopamine agonists only if the potential benefit outweighs the risk.
Impulse control disorders
Patients should be monitored regularly for the development of impulse control disorders. Patients and carers should be aware that behavioral symptoms of impulse control disorders, including pathological gambling, increased libido, hypersexuality, compulsive shopping or shopping, overeating and compulsive eating can occur in treated patients. with dopamine agonists including Requip Dose reduction / tapering should be considered if such symptoms develop.
Because of the risk of hypotension, in patients with severe cardiovascular disease (particularly coronary insufficiency), blood pressure monitoring is recommended, particularly at the start of treatment.
This medicine also contains lactose.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose or galactose malabsorption should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
There are no pharmacokinetic interactions between ropinirole and levodopa or domperidone which would require adjustment of the dosage of these medicinal products.
Neuroleptics and other centrally active dopamine antagonists, such as sulpiride or metoclopramide, may decrease the efficacy of ropinirole and therefore concomitant use of these medicinal products should be avoided.
Increased plasma concentrations of ropinirole have been observed in patients treated with high doses of estrogen. In patients already undergoing hormone replacement therapy (HRT), treatment with ropinirole can be initiated according to normal regimens. However, a dose adjustment of ropinirole may be necessary, depending on the clinical response, if hormone replacement therapy is started or stopped during treatment with ropinirole.
Ropinirole is mainly metabolised by cytochrome P450, the CYP1A2 isoenzyme. A pharmacokinetic study (with ropinirole at a dose of 2 mg, three times daily in parkinsonian patients) showed that ciprofloxacin increased the Cmax and AUC of ropinirole by 60% and 84% respectively, with a potential risk of adverse events. Therefore, in patients already being treated with ropinirole, a dose adjustment of ropinirole may be necessary if medicinal products known as CYP1A2 inhibitors, eg ciprofloxacin, enoxacin or fluvoxamine, are introduced or discontinued.
A pharmacokinetic interaction study in parkinsonian patients between ropinirole (at a dose of 2 mg, three times a day) and theophylline, a substrate of CYP1A2, showed no effect on the pharmacokinetics of ropinirole and theophylline.
Smoking is known to induce metabolism of CYP1A2, therefore if patients stop or start smoking while taking ropinirole, dose adjustment may be required.
Cases of INR abnormalities have been reported in patients treated with the combination of vitamin K antagonists and ropinirole. Increased clinical and biological vigilance (INR) should be ensured.
04.6 Pregnancy and lactation
Pregnancy
There are insufficient data from the use of ropinirole in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). As the potential risk to humans is unknown, it is recommended that ropinirole not be used during pregnancy unless the potential benefit to the patient outweighs the potential. risk to the fetus.
Feeding time
Ropinirole should not be used in breastfeeding mothers as it can inhibit lactation.
04.7 Effects on ability to drive and use machines
Patients on ropinirole who experience somnolence and / or episodes of sudden sleep attacks should be advised to refrain from driving or engaging in activities in which a lack of attention can put themselves or others at risk of serious harm or death ( e.g. operating machinery) until these recurrent episodes and somnolence have resolved (see section 4.4).
04.8 Undesirable effects
Side effects are listed below by system, organ, class and frequency. It is specified whether undesirable effects were reported in clinical trials as monotherapy or as add-on therapy to levodopa.
Frequencies are defined as follows: very common (> 1/10), common (> 1/100, 1 / 1,000, 1 / 10,000,
Within each frequency group, undesirable effects are presented in order of decreasing severity.
Disorders of the immune system
Not known hypersensitivity reactions (including urticaria, angioedema, rash, pruritus).
Psychiatric disorders
Common: hallucinations.
Uncommon: psychotic reactions (other than hallucinations) including severe confusion, delirium and paranoia.
Not known: aggression *
* aggression has been associated with psychotic reactions as well as compulsive symptoms.
Impulse control disorders (not known)
Pathological gambling, increased libido, hypersexuality, compulsive shopping or shopping, overeating and compulsive eating may occur in patients treated with dopamine agonists including Requip (see section 4.4 "Special warnings and precautions for use").
Use in adjunct therapy studies:
Common: confusion.
Nervous system disorders
Very common: somnolence
Common: dizziness (including vertigo)
Uncommon: episodes of sudden sleep attacks, excessive daytime sleepiness.
Ropinirole is associated with somnolence, less frequently associated with excessive daytime sleepiness and episodes of sudden sleep attacks.
Use in monotherapy studies:
Very common: syncope.
Use in adjunct therapy studies:
Very common: dyskinesia. In patients with advanced Parkinson's disease, dyskinesia may occur during the initial titration of ropinirole. In clinical studies it was shown that a reduction in the levodopa dose may improve dyskinesia (see section 4.2).
Vascular pathologies
Uncommon: postural hypotension, hypotension.
Postural hypotension or hypotension are rarely severe.
Gastrointestinal disorders
Very common: nausea.
Common: heartburn.
Use in monotherapy studies:
Common: vomiting, abdominal pain.
Hepatobiliary disorders
Not known: hepatic reactions, mainly increased liver enzymes.
General disorders and administration site conditions
Use in monotherapy studies:
Common: edema in the lower limbs.
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "address https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse
04.9 Overdose
Symptoms of ropinirole overdose are related to its dopaminergic activity. These symptoms can be alleviated by appropriate treatment with dopamine antagonists such as neuroleptics or metoclopramide.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: dopaminergic substances, dopamine agonists
ATC code: N04BC04.
Ropinirole is a non-ergolinic agonist of dopamine D2 / D3 receptors, which stimulates dopamine receptors in the striatum.
Ropinirole compensates for the dopamine deficiency that characterizes Parkinson's disease by stimulating the dopaminergic receptors of the striatum.
Ropinirole inhibits prolactin secretion in the hypothalamus and pituitary gland.
Study of the effect of ropinirole on cardiac repolarization
A thorough QT study conducted in healthy male and female volunteers who received doses of 0.5 - 1 - 2 and 4 mg film-coated (immediate-release) tablets once daily showed an increase in maximum duration of the QT interval at a dose of 1 mg, equal to 3.46 milliseconds (point estimate) compared to placebo. The upper limit of the one-sided 95% confidence interval for the largest mean effect was lower at 7.5 milliseconds. The effect of ropinirole at higher doses has not been systematically evaluated.
Clinical data available from a thorough QT study do not indicate a risk of QT prolongation at doses of ropinirole up to 4 mg per day. A risk of QT prolongation cannot be excluded as a thorough QT study at doses up to 24 mg has not been conducted.
05.2 "Pharmacokinetic properties
Absorption
The bioavailability of ropinirole is approximately 50% (36 - 57%). Ropinirole film-coated (immediate-release) tablets are rapidly absorbed orally, with peak concentrations of ropinirole occurring in a median of 1.5 hours after administration. A high-fat meal reduces the rate of absorption of ropinirole, as demonstrated by the delay in median T of 2.6 hours and an average 25% reduction in C.
Distribution
Plasma protein binding of ropinirole is low (10-40%).
Due to its high lipophilicity, ropinirole is characterized by a large volume of distribution (approximately 7 l / kg).
Biotransformation
Ropinirole is primarily metabolised by the cytochrome P450 enzyme CYP1A2, and its metabolites are predominantly excreted via the urine. The major metabolite is at least 100 times less potent than ropinirole in animal models of dopaminergic activity.
Elimination
Ropinirole is cleared from the systemic circulation with a mean elimination half-life of approximately 6 hours. The increase in systemic exposure to ropinirole (Cmax and AUC) is approximately proportional to the therapeutic dose range. clearance ropinirole has been observed following single and repeated oral administration. A large interindividual variability in pharmacokinetic parameters was observed.
Renal impairment
No changes in the pharmacokinetics of ropinirole were observed in Parkinson's disease patients with mild to moderate renal impairment.
In patients with end-stage renal disease undergoing regular hemodialysis, the clearance of ropinirole after oral administration is reduced by about 30%. Also there clearance metabolites SKF-104557 and SKF-89124 are reduced by approximately 80% and 60%, respectively, after oral administration. Therefore in these patients with Parkinson's disease the maximum recommended dose is limited to 18 mg per day (see section 4.2 ).
05.3 Preclinical safety data
Reproductive toxicity
Administration of ropinirole to pregnant rats, at doses toxic to mothers, resulted in reduced fetal body weight at a dose of 60 mg / kg / day (approximately twice the AUC at the maximum human dose), increased mortality fetal at 90 mg / kg / day (approximately 3 times the AUC at the maximum human dose) and digital malformations at 150 mg / kg / day (approximately 5 times the AUC at the maximum human dose). No teratogenic phenomena were observed in the rat at the dose of 120 mg / kg / day (approximately 4 times the AUC at the maximum human dose) and, in the rabbit, no signs of developmental effects were detected.
Toxicology
The toxicological profile is mainly determined by the pharmacological activity of ropinirole: changes in behavior, hypoprolactinemia, decrease in blood pressure and heart rate, ptosis and excessive salivation. Only in the albino rat, a degeneration of the retina was observed during a study long term at the highest dose (50 mg / kg / day), possibly associated with an increase in light exposure.
Genotoxicity
No genotoxic phenomena were observed in the usual studies in vitro And in vivo.
Carcinogenesis
During the two-year carcinogenicity studies conducted in mice and rats at doses up to 50 mg / kg / day, no manifestations of carcinogenicity were observed in mice. In the rat, the only lesions related to ropinirole treatment consisted of hyperplasia of Leydig cells and adenomas of the testis, attributable to the hypoprolactinemic effect induced by ropinirole. These lesions are considered a species specific phenomenon and such as not to constitute a risk although concerns the clinical use of ropinirole.
Pharmacological safety (Safety Pharmacology)
Education in vitro showed that ropinirole inhibits hERG-mediated currents. The IC50 is 5 times higher than the maximum expected plasma concentration in patients treated at the highest recommended doses (24 mg per day), see section 5.1.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablet core:
lactose monohydrate
microcrystalline cellulose
croscarmellose sodium
magnesium stearate.
Coating:
Requip 0.25 mg film-coated tablets:
hypromellose
macrogol 400
titanium dioxide (E171)
polysorbate 80 (E433)
Requip 0.5 mg film-coated tablets:
hypromellose
macrogol 400
titanium dioxide (E171)
yellow iron oxide (E172)
red iron oxide (E172)
indigo carmine lacquer (E132)
Requip 1 mg film-coated tablets:
hypromellose
macrogol 400
titanium dioxide (E171)
yellow iron oxide (E172)
indigo carmine lacquer (E132)
Requip 2 mg film-coated tablets:
hypromellose
macrogol 400
titanium dioxide (E171)
yellow iron oxide (E172)
red iron oxide (E172)
Requip 5 mg film-coated tablets:
hypromellose
macrogol 400
titanium dioxide (E171)
indigo carmine lacquer (E132)
polysorbate 80 (E433)
06.2 Incompatibility
Not relevant
06.3 Period of validity
2 years
06.4 Special precautions for storage
Do not store above 25 ° C
06.5 Nature of the immediate packaging and contents of the package
PVC / PCTFE / Aluminum or PVC / PCTFE / PVC / Aluminum blisters
Requip 0.25 mg film-coated tablets:
packs of 21, 126, 210 film-coated tablets
Requip 0.5 mg film-coated tablets:
packs of 21 film-coated tablets
Requip 1 mg film-coated tablets:
packs of 21, 84 film-coated tablets
Requip 2 mg film-coated tablets:
packs of 21, 84 film-coated tablets
Requip 5 mg film-coated tablets:
packs of 21, 84 film-coated tablets
60 ml HDPE bottle with aluminum foil seal and polypropylene cap
Pack size of 84 film-coated tablets
Not all pack sizes may be marketed.
06.6 Instructions for use and handling
No special instructions for disposal.
07.0 MARKETING AUTHORIZATION HOLDER
Laboratoire GlaxoSmithKline - 100 Route De Versailles - Marly-le-Roi - France
Legal and sales representative:
GlaxoSmithKline S.p.A. - Via A. Fleming, 2 - Verona
08.0 MARKETING AUTHORIZATION NUMBER
"0.25 mg film-coated tablets" 21 tablets in PVC / PCTFE / AL blister - A.I.C. n. 032261063
"0.25 mg film-coated tablets" 126 tablets in PVC / PCTFE / AL blister - A.I.C. n. 032261087
"0.25 mg film-coated tablets" 210 tablets in PVC / PCTFE / AL blister - A.I.C. n. 032261099
"0.25 mg film-coated tablets" 84 tablets in HDPE bottle - A.I.C. n. 032261075
"0.5 mg film-coated tablets" 21 tablets in PVC / PCTFE / AL blister - A.I.C. n. 032261101
"0.5 mg film-coated tablets" 84 tablets in HDPE bottle - A.I.C. n. 032261113
"1 mg film-coated tablets" 21 tablets in PVC / PCTFE / AL blister - A.I.C. n.032261125
"1 mg film-coated tablets" 84 tablets in HDPE bottle - A.I.C. n.032261137
"2 mg film-coated tablets" 21 tablets in PVC / PCTFE / AL blister - A.I.C. n. 032261149
"2 mg film-coated tablets" 84 tablets in HDPE bottle - A.I.C. n. 032261152
"5 mg film-coated tablets" 21 tablets in PVC / PCTFE / AL blister - A.I.C. n. 032261164
"5 mg film-coated tablets" 84 tablets in HDPE bottle - A.I.C. n. 032261176
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
17.12.1996 / March 2009
10.0 DATE OF REVISION OF THE TEXT
22 April 2014
