Mefac may be available in the countries listed below.
Mefenamic Acid is reported as an ingredient of Mefac in the following countries:
International Drug Name Search
Avimycin may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Usnic Acid is reported as an ingredient of Avimycin in the following countries:
International Drug Name Search
Pravastatina Pritanol may be available in the countries listed below.
Pravastatin sodium salt (a derivative of Pravastatin) is reported as an ingredient of Pravastatina Pritanol in the following countries:
International Drug Name Search
Butosol may be available in the countries listed below.
Beclometasone 17α,21-dipropionate (a derivative of Beclometasone) is reported as an ingredient of Butosol in the following countries:
Salbutamol is reported as an ingredient of Butosol in the following countries:
International Drug Name Search
Clorexifarm may be available in the countries listed below.
Chlorhexidine digluconate (a derivative of Chlorhexidine) is reported as an ingredient of Clorexifarm in the following countries:
International Drug Name Search
Fositen may be available in the countries listed below.
Fosinopril is reported as an ingredient of Fositen in the following countries:
Fosinopril sodium salt (a derivative of Fosinopril) is reported as an ingredient of Fositen in the following countries:
International Drug Name Search
Itamol may be available in the countries listed below.
Paracetamol is reported as an ingredient of Itamol in the following countries:
International Drug Name Search
Metrobac may be available in the countries listed below.
Metronidazole is reported as an ingredient of Metrobac in the following countries:
International Drug Name Search
Cimolan may be available in the countries listed below.
Carbocisteine is reported as an ingredient of Cimolan in the following countries:
International Drug Name Search
Klindamicin may be available in the countries listed below.
Clindamycin is reported as an ingredient of Klindamicin in the following countries:
International Drug Name Search
Fluoxifar may be available in the countries listed below.
Fluoxetine hydrochloride (a derivative of Fluoxetine) is reported as an ingredient of Fluoxifar in the following countries:
International Drug Name Search
Ciprofibrate Teva may be available in the countries listed below.
Ciprofibrate is reported as an ingredient of Ciprofibrate Teva in the following countries:
International Drug Name Search
Furosemid-ratiopharm may be available in the countries listed below.
Furosemide is reported as an ingredient of Furosemid-ratiopharm in the following countries:
Furosemide sodium (a derivative of Furosemide) is reported as an ingredient of Furosemid-ratiopharm in the following countries:
International Drug Name Search
Fastanil may be available in the countries listed below.
Famotidine is reported as an ingredient of Fastanil in the following countries:
International Drug Name Search
Pralmorelin Dihydrochloride may be available in the countries listed below.
Pralmorelin Dihydrochloride (USAN) is also known as Pralmorelin (Rec.INN)
International Drug Name Search
Glossary
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Corel may be available in the countries listed below.
Carvedilol is reported as an ingredient of Corel in the following countries:
International Drug Name Search
Tramadolor ID may be available in the countries listed below.
Tramadol hydrochloride (a derivative of Tramadol) is reported as an ingredient of Tramadolor ID in the following countries:
International Drug Name Search
Ciprofloxacina Sandoz may be available in the countries listed below.
Ciprofloxacin hydrochloride (a derivative of Ciprofloxacin) is reported as an ingredient of Ciprofloxacina Sandoz in the following countries:
International Drug Name Search
Eritropiù may be available in the countries listed below.
Ferrous Gluconate is reported as an ingredient of Eritropiù in the following countries:
International Drug Name Search
Globaxol may be available in the countries listed below.
Sulfamethoxazole is reported as an ingredient of Globaxol in the following countries:
Trimethoprim is reported as an ingredient of Globaxol in the following countries:
International Drug Name Search
Pritacort may be available in the countries listed below.
Dexamethasone is reported as an ingredient of Pritacort in the following countries:
Dexchlorpheniramine maleate (a derivative of Dexchlorpheniramine) is reported as an ingredient of Pritacort in the following countries:
International Drug Name Search
In the US, Enfuvirtide (enfuvirtide systemic) is a member of the drug class miscellaneous antivirals and is used to treat HIV Infection.
US matches:
Rec.INN
J05AX07
0159519-65-0
C204-H301-N51-O64
4492
Antiviral agent, treatment of HIV infection
Acetyl-L-tyrosyl-L-threonyl-L-seryl-L-leucyl-L-isoleucyl-L-histidyl-L-seryl-L-leucyl-L-isoleucyl-L-α-glutamyl-L-α-glutamyl-L-seryl-L-glutaminyl-L-asparaginyl-L-glutaminyl-L-glutaminyl-L-α-glutamyl-L-lysyl-L-asparaginyl-L-α-glutamyl-L-glutaminyl-L-α-glutam (WHO)
International Drug Name Search
Glossary
| BAN | British Approved Name |
| IS | Inofficial Synonym |
| OS | Official Synonym |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
| WHO | World Health Organization |
Predlitem may be available in the countries listed below.
Methylprednisolone 21-(sodium succinate) (a derivative of Methylprednisolone) is reported as an ingredient of Predlitem in the following countries:
International Drug Name Search
Alfoxil may be available in the countries listed below.
Amoxicillin is reported as an ingredient of Alfoxil in the following countries:
International Drug Name Search
Toufilex may be available in the countries listed below.
Tenoic Acid sodium salt (a derivative of Tenoic Acid) is reported as an ingredient of Toufilex in the following countries:
International Drug Name Search
Gentamicina Iqfarma may be available in the countries listed below.
Gentamicin is reported as an ingredient of Gentamicina Iqfarma in the following countries:
International Drug Name Search
Aprotinine may be available in the countries listed below.
Aprotinine (DCF) is known as Aprotinin in the US.
International Drug Name Search
Glossary
| DCF | Dénomination Commune Française |
Triamtereen-Hydrochloorthiazide ratiopharm may be available in the countries listed below.
Hydrochlorothiazide is reported as an ingredient of Triamtereen-Hydrochloorthiazide ratiopharm in the following countries:
Triamterene is reported as an ingredient of Triamtereen-Hydrochloorthiazide ratiopharm in the following countries:
International Drug Name Search
In the US, Cartia XT (diltiazem systemic) is a member of the following drug classes: calcium channel blocking agents, group IV antiarrhythmics and is used to treat Angina Pectoris Prophylaxis, Atrial Fibrillation, Atrial Flutter, Heart Failure, High Blood Pressure, Raynaud's Syndrome and Supraventricular Tachycardia.
US matches:
Diltiazem hydrochloride (a derivative of Diltiazem) is reported as an ingredient of Cartia XT in the following countries:
International Drug Name Search
Crima may be available in the countries listed below.
Ceftazidime pentahydrate (a derivative of Ceftazidime) is reported as an ingredient of Crima in the following countries:
International Drug Name Search
Tryptizol may be available in the countries listed below.
Amitriptyline hydrochloride (a derivative of Amitriptyline) is reported as an ingredient of Tryptizol in the following countries:
International Drug Name Search
Indextol may be available in the countries listed below.
Dexamethasone is reported as an ingredient of Indextol in the following countries:
International Drug Name Search
Epilat may be available in the countries listed below.
Nifedipine is reported as an ingredient of Epilat in the following countries:
International Drug Name Search
In the US, Constilac is a member of the drug class laxatives and is used to treat Constipation - Acute, Constipation - Chronic and Hepatic Encephalopathy.
Lactulose is reported as an ingredient of Constilac in the following countries:
International Drug Name Search
Advocid may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Danofloxacin mesilate (a derivative of Danofloxacin) is reported as an ingredient of Advocid in the following countries:
International Drug Name Search
Losartan La Santé may be available in the countries listed below.
Losartan potassium salt (a derivative of Losartan) is reported as an ingredient of Losartan La Santé in the following countries:
International Drug Name Search
Alendronsäure AbZ may be available in the countries listed below.
Alendronic Acid sodium trihydrate (a derivative of Alendronic Acid) is reported as an ingredient of Alendronsäure AbZ in the following countries:
International Drug Name Search
Ketanarkon may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Ketamine hydrochloride (a derivative of Ketamine) is reported as an ingredient of Ketanarkon in the following countries:
International Drug Name Search
Flucosan may be available in the countries listed below.
Fluconazole is reported as an ingredient of Flucosan in the following countries:
International Drug Name Search
Hisnul may be available in the countries listed below.
Chlorphenamine maleate (a derivative of Chlorphenamine) is reported as an ingredient of Hisnul in the following countries:
International Drug Name Search
Rocornal may be available in the countries listed below.
Trapidil is reported as an ingredient of Rocornal in the following countries:
International Drug Name Search
Besemax may be available in the countries listed below.
Orphenadrine citrate (a derivative of Orphenadrine) is reported as an ingredient of Besemax in the following countries:
Paracetamol is reported as an ingredient of Besemax in the following countries:
International Drug Name Search
Rec.INN
V08CA01
0080529-93-7
C14-H20-Gd-N3-O10
547
Contrast medium, NMR-tomography
Gadolinate(2-), [N,N-bis[2-[bis(carboxymethyl)amino]ethyl]glycinato(5-)]-, dihydrogen
International Drug Name Search
Glossary
| BAN | British Approved Name |
| BANM | British Approved Name (Modified) |
| DCF | Dénomination Commune Française |
| IS | Inofficial Synonym |
| JAN | Japanese Accepted Name |
| OS | Official Synonym |
| PH | Pharmacopoeia Name |
| Rec.INN | Recommended International Nonproprietary Name (World Health Organization) |
| USAN | United States Adopted Name |
Pseudoefedrina may be available in the countries listed below.
Pseudoefedrina (DCIT) is known as Pseudoephedrine in the US.
International Drug Name Search
Glossary
| DCIT | Denominazione Comune Italiana |
Bisoprolol Mylan may be available in the countries listed below.
Bisoprolol fumarate (a derivative of Bisoprolol) is reported as an ingredient of Bisoprolol Mylan in the following countries:
International Drug Name Search
Mephenon may be available in the countries listed below.
Methadone hydrochloride (a derivative of Methadone) is reported as an ingredient of Mephenon in the following countries:
International Drug Name Search
Cilamox may be available in the countries listed below.
Amoxicillin trihydrate (a derivative of Amoxicillin) is reported as an ingredient of Cilamox in the following countries:
International Drug Name Search
Bresec may be available in the countries listed below.
Ceftriaxone disodium salt (a derivative of Ceftriaxone) is reported as an ingredient of Bresec in the following countries:
International Drug Name Search
Thalix may be available in the countries listed below.
Thalidomide is reported as an ingredient of Thalix in the following countries:
International Drug Name Search
Minotab may be available in the countries listed below.
Minocycline is reported as an ingredient of Minotab in the following countries:
Minocycline hydrochloride (a derivative of Minocycline) is reported as an ingredient of Minotab in the following countries:
International Drug Name Search
Rectanal may be available in the countries listed below.
Sodium Phosphate Dibasic dodecahydrate (a derivative of Sodium Phosphate) is reported as an ingredient of Rectanal in the following countries:
Sodium Phosphate Monobasic dihydrate (a derivative of Sodium Phosphate) is reported as an ingredient of Rectanal in the following countries:
International Drug Name Search
Cuprenil may be available in the countries listed below.
Penicillamine is reported as an ingredient of Cuprenil in the following countries:
International Drug Name Search
Mestamox may be available in the countries listed below.
Amoxicillin trihydrate (a derivative of Amoxicillin) is reported as an ingredient of Mestamox in the following countries:
International Drug Name Search
Hysan Nasenspray may be available in the countries listed below.
Hyaluronic Acid sodium salt (a derivative of Hyaluronic Acid) is reported as an ingredient of Hysan Nasenspray in the following countries:
International Drug Name Search
Promethazine hydrochloride (a derivative of Promethazine) is reported as an ingredient of Promethacon in the following countries:
International Drug Name Search
Antiphlogistine may be available in the countries listed below.
Salicylic Acid is reported as an ingredient of Antiphlogistine in the following countries:
International Drug Name Search
Prosimed may be available in the countries listed below.
Fluoxetine is reported as an ingredient of Prosimed in the following countries:
International Drug Name Search
Pro-Ambrosan may be available in the countries listed below.
Ambroxol hydrochloride (a derivative of Ambroxol) is reported as an ingredient of Pro-Ambrosan in the following countries:
International Drug Name Search
Katenomin may be available in the countries listed below.
Atenolol is reported as an ingredient of Katenomin in the following countries:
International Drug Name Search
Finasterid may be available in the countries listed below.
Finasteride is reported as an ingredient of Finasterid in the following countries:
International Drug Name Search
Clodronato Teva may be available in the countries listed below.
Clodronic Acid disodium tetrahydrate (a derivative of Clodronic Acid) is reported as an ingredient of Clodronato Teva in the following countries:
International Drug Name Search
Carbocisteina Francia may be available in the countries listed below.
Carbocisteine is reported as an ingredient of Carbocisteina Francia in the following countries:
International Drug Name Search
Riboquin may be available in the countries listed below.
Chloroquine phosphate (a derivative of Chloroquine) is reported as an ingredient of Riboquin in the following countries:
International Drug Name Search
Methotrexate Ebewe may be available in the countries listed below.
Methotrexate is reported as an ingredient of Methotrexate Ebewe in the following countries:
International Drug Name Search
Gambaran may be available in the countries listed below.
Nabumetone is reported as an ingredient of Gambaran in the following countries:
International Drug Name Search
Reverin may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Oxytetracycline is reported as an ingredient of Reverin in the following countries:
International Drug Name Search
Gabexal may be available in the countries listed below.
Gabapentin is reported as an ingredient of Gabexal in the following countries:
International Drug Name Search
Inciwag may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Pyrethrin I is reported as an ingredient of Inciwag in the following countries:
International Drug Name Search
Metronidazol DAK may be available in the countries listed below.
Metronidazole is reported as an ingredient of Metronidazol DAK in the following countries:
International Drug Name Search
Protace may be available in the countries listed below.
Ramipril is reported as an ingredient of Protace in the following countries:
International Drug Name Search
Biotonus may be available in the countries listed below.
Mosapride is reported as an ingredient of Biotonus in the following countries:
International Drug Name Search
Gemci-cell may be available in the countries listed below.
Gemcitabine hydrochloride (a derivative of Gemcitabine) is reported as an ingredient of Gemci-cell in the following countries:
International Drug Name Search
Tetraseptin may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Tetracycline is reported as an ingredient of Tetraseptin in the following countries:
Tetracycline hydrochloride (a derivative of Tetracycline) is reported as an ingredient of Tetraseptin in the following countries:
International Drug Name Search
Glycomin may be available in the countries listed below.
Glibenclamide is reported as an ingredient of Glycomin in the following countries:
International Drug Name Search
Flosep may be available in the countries listed below.
Ofloxacin is reported as an ingredient of Flosep in the following countries:
International Drug Name Search
Egogyn may be available in the countries listed below.
Estradiol is reported as an ingredient of Egogyn in the following countries:
Levonorgestrel is reported as an ingredient of Egogyn in the following countries:
Tocopherol, α- is reported as an ingredient of Egogyn in the following countries:
Tocopherol, α- acetate (a derivative of Tocopherol, α-) is reported as an ingredient of Egogyn in the following countries:
International Drug Name Search
Modacin may be available in the countries listed below.
Ceftazidime pentahydrate (a derivative of Ceftazidime) is reported as an ingredient of Modacin in the following countries:
International Drug Name Search
Buscofen may be available in the countries listed below.
Ibuprofen is reported as an ingredient of Buscofen in the following countries:
International Drug Name Search
Ficonax may be available in the countries listed below.
Metformin hydrochloride (a derivative of Metformin) is reported as an ingredient of Ficonax in the following countries:
International Drug Name Search
Jasoquin may be available in the countries listed below.
Quinine dihydrochloride (a derivative of Quinine) is reported as an ingredient of Jasoquin in the following countries:
International Drug Name Search
Arcelenan may be available in the countries listed below.
Domperidone is reported as an ingredient of Arcelenan in the following countries:
International Drug Name Search
Tenoxicam Alternova may be available in the countries listed below.
Tenoxicam is reported as an ingredient of Tenoxicam Alternova in the following countries:
International Drug Name Search
Arcasin may be available in the countries listed below.
Phenoxymethylpenicillin potassium (a derivative of Phenoxymethylpenicillin) is reported as an ingredient of Arcasin in the following countries:
International Drug Name Search
Resotyl may be available in the countries listed below.
Modafinil is reported as an ingredient of Resotyl in the following countries:
International Drug Name Search
Bridic may be available in the countries listed below.
Brivudine is reported as an ingredient of Bridic in the following countries:
International Drug Name Search
Griseofulvin SG may be available in the countries listed below.
Griseofulvin is reported as an ingredient of Griseofulvin SG in the following countries:
International Drug Name Search
C-Serum Gel may be available in the countries listed below.
Ascorbic Acid is reported as an ingredient of C-Serum Gel in the following countries:
International Drug Name Search
Phénytoïne may be available in the countries listed below.
Phénytoïne (DCF) is known as Phenytoin in the US.
International Drug Name Search
Glossary
| DCF | Dénomination Commune Française |
Bio Energol Plus may be available in the countries listed below.
Arginine aspartate (a derivative of Arginine) is reported as an ingredient of Bio Energol Plus in the following countries:
International Drug Name Search
Kimotab may be available in the countries listed below.
Bromelains is reported as an ingredient of Kimotab in the following countries:
Trypsin is reported as an ingredient of Kimotab in the following countries:
International Drug Name Search
Peptoran may be available in the countries listed below.
Ranitidine is reported as an ingredient of Peptoran in the following countries:
Ranitidine hydrochloride (a derivative of Ranitidine) is reported as an ingredient of Peptoran in the following countries:
International Drug Name Search
Cobiona may be available in the countries listed below.
Oxatomide is reported as an ingredient of Cobiona in the following countries:
International Drug Name Search
Carbo-cell may be available in the countries listed below.
Carboplatin is reported as an ingredient of Carbo-cell in the following countries:
International Drug Name Search
Tenafin may be available in the countries listed below.
Butenafine hydrochloride (a derivative of Butenafine) is reported as an ingredient of Tenafin in the following countries:
International Drug Name Search
Meniace may be available in the countries listed below.
Betahistine dimesilate (a derivative of Betahistine) is reported as an ingredient of Meniace in the following countries:
International Drug Name Search
Triflumann may be available in the countries listed below.
Trifluridine is reported as an ingredient of Triflumann in the following countries:
International Drug Name Search
Piton-S may be available in the countries listed below.
Oxytocin is reported as an ingredient of Piton-S in the following countries:
International Drug Name Search
Minprog may be available in the countries listed below.
Alprostadil is reported as an ingredient of Minprog in the following countries:
International Drug Name Search
Cipla-Duovir may be available in the countries listed below.
Lamivudine is reported as an ingredient of Cipla-Duovir in the following countries:
Zidovudine is reported as an ingredient of Cipla-Duovir in the following countries:
International Drug Name Search
Asmanyl may be available in the countries listed below.
Theophylline is reported as an ingredient of Asmanyl in the following countries:
International Drug Name Search
Atropine Sulfate (USAN) is known as Atropine in the US.
International Drug Name Search
Glossary
| USAN | United States Adopted Name |
Fludex retard may be available in the countries listed below.
Indapamide is reported as an ingredient of Fludex retard in the following countries:
International Drug Name Search
Apo-Flecainide may be available in the countries listed below.
Flecainide acetate (a derivative of Flecainide) is reported as an ingredient of Apo-Flecainide in the following countries:
International Drug Name Search
Tranky may be available in the countries listed below.
Sildenafil citrate (a derivative of Sildenafil) is reported as an ingredient of Tranky in the following countries:
International Drug Name Search
A-Lennon Fluoxetine may be available in the countries listed below.
Fluoxetine hydrochloride (a derivative of Fluoxetine) is reported as an ingredient of A-Lennon Fluoxetine in the following countries:
International Drug Name Search
Fungizyn may be available in the countries listed below.
Miconazole nitrate (a derivative of Miconazole) is reported as an ingredient of Fungizyn in the following countries:
International Drug Name Search
Féligastryl may be available in the countries listed below.
In some countries, this medicine may only be approved for veterinary use.
Eseridine salicylate (a derivative of Eseridine) is reported as an ingredient of Féligastryl in the following countries:
International Drug Name Search
Requip® XL 2, 4 or 8 mg prolonged-release tablets.
2 / 4 / 8 mg ropinirole (as hydrochloride).
Excipient(s):
Lactose
Sunset yellow (E110) - 4 mg only
For a full list of excipients, see section 6.1.
Prolonged-release tablet.
2 mg: Pink capsule-shaped, film-coated tablets marked "GS" on one side and "3V2" on the other.
4 mg: Light brown capsule-shaped, film-coated tablets marked "GS" on one side and "WXG" on the other.
8 mg: Red capsule-shaped, film-coated tablets marked "GS" on one side and "5CC" on the other.
Treatment of Parkinson's disease under the following conditions:
• Initial treatment as monotherapy, in order to delay the introduction of levodopa
• In combination with levodopa, over the course of the disease, when the effect of levodopa wears off or becomes inconsistent and fluctuations in the therapeutic effect occur (“end of dose” or “on-off” type fluctuations)
Oral use.
Individual dose titration against efficacy and tolerability is recommended. Ropinirole prolonged-release tablets should be taken once a day and at a similar time each day. The tablets must be swallowed whole and must not be chewed, crushed or divided.
The tablets may be taken with or without food. A high fat meal may double the AUC and Cmax in some individuals (See 5.2 Pharmacokinetics).
Adults
Initial titration
The starting dose of ropinirole prolonged-release tablets is 2 mg once daily for the first week; this should be increased to 4 mg once daily from the second week of treatment. A therapeutic response may be seen at a dose of 4 mg once daily of ropinirole prolonged-release tablets.
Patients who initiate treatment with a dose of 2 mg/day of ropinirole prolonged-release tablets and who experience side effects that they cannot tolerate, may benefit from switching to treatment with ropinirole film-coated (immediate release) tablets at a lower daily dose, divided into three equal doses.
Therapeutic regimen
Patients should be maintained on the lowest dose of ropinirole prolonged-release tablets that achieves symptomatic control.
If sufficient symptomatic control is not achieved or maintained at a dose of 4 mg once daily of ropinirole prolonged-release tablets, the daily dose may be increased by 2 mg at weekly or longer intervals up to a dose of 8 mg once daily of prolonged-release tablets.
If sufficient symptomatic control is still not achieved or maintained at a dose of 8 mg once daily of ropinirole prolonged-release tablets, the daily dose may be increased by 2 mg to 4 mg at two weekly or longer intervals. The maximum daily dose of ropinirole prolonged-release tablets is 24 mg.
It is recommended that patients are prescribed the minimum number of ropinirole prolonged-release tablets that are necessary to achieve the required dose by utilising the highest available strengths of ropinirole prolonged-release tablets.
When ropinirole prolonged-release tablets are administered as adjunct therapy to levodopa, it may be possible to gradually reduce the levodopa dose, depending on the clinical response. In clinical trials, the levodopa dose was reduced gradually by approximately 30% in patients receiving ropinirole prolonged-release tablets concurrently. In patients with advanced Parkinson's disease receiving ropinirole prolonged-release tablets in combination with L-dopa, dyskinesias can occur during the initial titration of ropinirole prolonged-release tablets. In clinical trials it was shown that a reduction of the L-dopa dose may ameliorate dyskinesia (see also 4.8 Undesirable effects).
When switching treatment from another dopamine agonist to ropinirole, the marketing authorisation holder's guidance on discontinuation should be followed before initiating ropinirole.
As with other dopamine agonists, it is necessary to discontinue ropinirole treatment gradually by reducing the daily dose over the period of one week.
Switching from ropinirole immediate release tablets to ropinirole prolonged-release tablets
Patients may be switched overnight from ropinirole immediate release tablets to ropinirole prolonged-release tablets.
The dose of ropinirole prolonged-release tablets should be based on the total daily dose of immediate release formulation that the patient was receiving. The recommended dose for switching from ropinirole immediate release tablets to ropinirole prolonged-release tablets are provided in the following table. If patients are taking a different total daily dose of ropinirole immediate release tablets to those typically prescribed doses as shown in the table, they should be switched to the nearest available dose of ropinirole prolonged-release tablets as stated in the table:
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After switching to Requip XL prolonged-release tablets, the dose may be adjusted depending on the therapeutic response (see “Initial titration” and “Therapeutic regimen” above).
Dose interruption or discontinuation
If treatment is interrupted for one day or more, re-initiation by dose titration on ropinirole immediate release tablets should be considered.
If it is necessary to discontinue ropinirole treatment, this should be done gradually by reducing the daily dose over the period of one week.
Renal impairment
In parkinsonian patients with mild to moderate renal impairment (creatinine clearance between 30 and 50 ml/min) no change in the clearance of ropinirole was observed, indicating that no dosage adjustment is necessary in this population.
A study into the use of ropinirole in patients with end stage renal disease (patients on haemodialysis) has shown that a dose adjustment in these patients is required as follows:
The recommended initial dose of ReQuip XL is 2 mg once daily. Further dose escalations should be based on tolerability and efficacy. The recommended maximum dose is 18 mg/day in patients receiving regular dialysis. Supplemental doses after dialysis are not required.
The use of ropinirole in patients with severe renal impairment (creatinine clearance less than 30 ml/min) without regular haemodialysis has not been studied.
Hepatic impairment
The use of ropinirole in patients with hepatic impairment has not been studied. Administration of ropinirole to such patients is not recommended.
Elderly
The clearance of ropinirole is decreased by approximately 15% in patients aged 65 years or above. Although a dose adjustment is not required, ropinirole dose should be individually titrated, with careful monitoring of tolerability, to the optimal clinical response. In patients aged 75 years and above, slower titration during treatment initiation may be considered.
Children and adolescents
Ropinirole prolonged-release tablets are not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy.
Hypersensitivity to ropinirole or to any of the excipients.
Severe renal impairment (creatinine clearance <30 ml/min) without regular haemodialysis.
Hepatic impairment.
Due to the risk of hypotension, blood pressure monitoring is recommended, particularly at the start of treatment, in patients with severe cardiovascular disease (in particular coronary insufficiency).
Patients with a history or presence of major psychotic disorders should only be treated with dopamine agonists if the potential benefits outweigh the risks (see also section 4.5).
Impulse control disorders including pathological gambling, increased libido and hypersexuality have been reported in patients treated with dopamine agonists for Parkinson's disease, including ropinirole. Those disorders were reported especially at high doses and were generally reversible upon reduction of the dose or treatment discontinuation. Risk factors such as a history of compulsive behaviours were present in some cases (see section 4.8).
Ropinirole has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with ropinirole. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered.
This medicinal product also contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The 4 mg tablets contain the azo colouring agent sunset yellow (E110), which may cause allergic reactions.
There is no pharmacokinetic interaction between ropinirole and L-dopa or domperidone which would necessitate dosage adjustment of these drugs. Neuroleptics and other centrally active dopamine antagonists, such as sulpiride or metoclopramide, may diminish the effectiveness of ropinirole and therefore, concomitant use of these medicinal products should be avoided.
Ropinirole is principally metabolised by the cytochrome P450 enzyme CYP1A2. A pharmacokinetic study (with a ropinirole film-coated (immediate-release) tablet dose of 2 mg, three times a day) in Parkinson's disease patients, revealed that ciprofloxacin increased the Cmax and AUC of ropinirole by 60% an 84% respectively, with a potential risk of adverse events. Hence, in patients already receiving ropinirole, the dose of ropinirole may need to be adjusted when medicinal products know to inhibit CYP1A2, e.g. ciprofloxacin, enoxacin, cimetidine or fluvoxamine, are introduced or withdrawn.
A pharmacokinetic interaction study in patients with Parkinson's disease between ropinirole (with a ropinirole film-coated (immediate-release) tablet dose of 2 mg, three times a day) and theophylline, a substrate of CYP1A2, revealed no change in the pharmacokinetics of either ropinirole or theophylline.
Increased plasma concentrations of ropinirole have been observed in patients treated with high doses of oestrogens. In patients already receiving hormone replacement therapy (HRT), ropinirole treatment may be initiated in the normal manner. However, if HRT is stopped or introduced during treatment with ropinirole, dosage adjustment may be required.
Smoking is known to induce CYP1A2 metabolism, therefore if patients stop or start smoking during treatment with ropinirole, adjustment of dose may be required.
There are no adequate data from the use of ropinirole in pregnant women.
Studies in animals have shown reproductive toxicity (see section 5.3). As the potential risk for humans is unknown, it is recommended that ropinirole is not used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the foetus.
Ropinirole should not be used in nursing mothers as it may inhibit lactation.
No human fertility data are available.
Ropinirole may have a major effect on the ability to drive and use machines.
Patients being treated with ropinirole and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until such recurrent episodes and somnolence have resolved (see also section 4.4).
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000) very rare (<1/10,000), not known (cannot be estimated from the available data).
During clinical trials, the most commonly reported undesirable effects for ropinirole prolonged-release tablets were during monotherapy and dyskinesia during adjunctive therapy with levodopa.
The following adverse events were reported during clinical trials with ReQuip XL up to 24 mg/day.
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In addition to the above adverse drug reactions, the following events have been reported with ReQuip film-coated (immediate-release) tablets in patients with Parkinson's disease during clinical trials (at doses up to 24 mg/day) and/or post-marketing reports,
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The symptoms of ropinirole overdose are generally related to its dopaminergic activity. These symptoms may be alleviated by appropriate treatment with dopamine antagonists such as neuroleptics or metoclopramide.
Pharmacotherapeutic group
Dopamine agonist.
ATC code: N04BC04
Mechanism of action
Parkinson's disease is characterised by a marked dopamine deficiency in the nigral striatal system. Ropinirole is a non-ergoline D2/D3 dopamine agonist that alleviates this deficiency by stimulating striatal dopamine receptors.
Ropinirole acts in the hypothalamus and pituitary to inhibit the secretion of prolactin.
Clinical efficacy
A 36-week, double-blind, three-period crossover study, in monotherapy with a primary end point of change from period baseline in Unified Parkinson's Disease Rating Scale (UPDRS) total motor score was conducted in 161 patients with early phase Parkinson's disease. A subgroup analysis of patients initiated on monotherapy treatment with ropinirole immediate release tablets and switched overnight to the nearest equivalent dose of ropinirole prolonged-release tablets was consistent with similar efficacy from equivalent mg for mg doses. The adjusted mean difference between ropinirole prolonged-release tablets and Requip film-coated (immediate-release) tablets at study-endpoint was 0.7 points (95% CI: [-1.51, 0.10], p=0.0842).
Following the overnight switch to a similar dose of the alternative tablet formulation, there was no difference in the adverse event profile and less than 3% of patients required a dose adjustment (all dose adjustments were increases by one dose level. No patients required a dose increase).
A 24-week, double-blind, placebo-controlled, parallel group study in patients with Parkinson's disease who were not optimally controlled on levodopa demonstrated that adjunctive therapy of ropinirole prolonged-release tablets results in clinically relevant and statistically significant superiority over placebo in a change from baseline in awake time “off” (adjusted mean treatment difference -1.7 hours (95% CI: [-2.34, -1.09], p<0.0001). This was supported by secondary efficacy parameters of change from baseline in total awake time “on” (+1.7 hours (95% CI [1.06, 2.33], p<0.0001) and total awake time “on” without troublesome dyskinesias (+1.5 hours (95% CI: [0.85, 2.13], p<0.0001). Importantly, there was no indication of an increase from baseline in awake time “on” with troublesome dyskinesias, either from diary card data or from the UPDRS items.
Study of the effect of ropinirole on cardiac repolarisation
A thorough QT study conducted in male and female healthy volunteers who received doses of 0.5, 1, 2 and 4 mg of ropinirole film-coated (immediate release) tablets once daily showed a maximum increase of the QT interval duration nat the 1 mg dose of 3.46 milliseconds (point estimate) as compared to placebo. The upper bound of the one sided 95% confidence interval for the largest mean effect was less than 7.5 milliseconds. The effect of ropinirole at higher doses has not been systematically evaluated.
The available clinical data from a thorough QT study do not indicate a risk of QT prolongation at doses of ropinirole up to 4 mg/day. A risk of QT prolongation cannot be excluded as a thorough QT study at doses up to 24 mg/day has not been conducted.
Absorption
Bioavailability of ropinirole is approximately 50% (36–57%). Following oral administration of ropinirole prolonged-release tablets, plasma concentrations of ropinirole increase slowly, with a median time to Cmax of between six and ten hours.
In a steady-state study in Parkinson's disease patients receiving 12 mg of Requip XL once daily, a high fat meal increased the systemic exposure to ropinirole as shown by an average 20% increase in AUC (90% CI [1.12, 1.28]) and an average 44% increase in Cmax (90% CI[1.34, 1.56]). Tmax was delayed by 3.0 hours. However, in the studies that established the safety and efficacy of Requip XL, patients were instructed to take study medication without regard to food intake.
The systemic exposure to ropinirole is comparable for ropinirole prolonged-release tablets and ropinirole film-coated (immediate-release) tablets based on the same daily dose.
Distribution
Plasma protein binding of the drug is low (10–40%). Consistent with its high lipophilicity, ropinirole exhibits a large volume of distribution (approximately 7 l/kg).
Metabolism
Ropinirole is primarily cleared by CYP1A2 metabolism and its metabolites are mainly excreted in the urine. The major metabolite is at least 100-times less potent than ropinirole in animal models of dopaminergic function.
Elimination
Ropinirole is cleared from the systemic circulation with an average elimination half-life of about six hours. The increase in systemic exposure (Cmax and AUC) to ropinirole is approximately proportional over the therapeutic dose range. No change in the oral clearance of ropinirole is observed following single and repeated oral administration. Wide inter-individual variability in the pharmacokinetic parameters has been observed. Following steady-state administration of ropinirole prolonged-release tablets, the inter-individual variability of Cmax was between 30% and 55% and for AUC was between 40% and 70%.
Special Patient Populations
Renal impairment: There was no change observed in the pharmacokinetics of ropinirole in Parkinson's disease patients with mild to moderate renal impairment.
In patients with end stage renal disease receiving regular dialysis, oral clearance of ropinirole is reduced by approximately 30%. Oral clearance of the metabolites SKF-104557 and SKF-89124 were also reduced by approximately 80% and 60%, respectively. Therefore, the recommended maximum dose is limited to 18 mg/day in these patients with Parkinson's disease.
Reproductive toxicity
Administration of ropinirole to pregnant rats at maternally toxic doses resulted in decreased foetal body weight at 60 mg/kg/day (approximately twice the AUC at the maximum dose in humans), increased foetal death at 90 mg/kg/day (approximately 3 times the AUC at the maximum dose in humans) and digit malformations at 150 mg/kg/day (approximately 5 times the AUC at the maximum dose in humans). There were no teratogenic effects in the rat at 120 mg/kg/day (approximately 4 times the AUC at the maximum dose in humans) and no indication of an effect on development in the rabbit.
General toxicology
The toxicology profile is principally determined by the pharmacological activity of the drug (behavioural changes, hypoprolactinaemia, decrease in blood pressure and heart rate, ptosis and salivation). In the albino rat only, retinal degeneration ws observed in a long term study at the highest dose (50 mg/kg/day), and was probably associated with an increased exposure to light.
Genotoxicity
Genotoxicity was not observed in a battery of in vitro and in vivo tests.
Carcinogenicity
Two-year studies have been conducted in the mouse and rat at dosages up to 50 mg/kg. The mouse study did not reveal any carcinogenic effect. In the rat, the only drug-related lesions were Leydig cell hyperplasia/adenoma in the testis resulting from the hypoprolactinaemic effect of ropinirole. These lesions are considered to be a species specific phenomenon and do not constitute a hazard with regard to the clinical use of ropinirole.
Safety pharmacology
In vitro studies have shown that ropinirole inhibits hERG-mediated currents. The IC50 is 5-fold higher than the expected maximum plasma concentration in patients treated at the highest recommended dose (24 mg/day), see section 5.1.
Tablet core
Hypromellose 2208, hydrogenated castor oil, carmellose sodium, povidone K29-32, maltodextrin, magnesium stearate, lactose monohydrate, anhydrous colloidal silica, mannitol (E421), ferric oxide yellow (E172) and glycerol dibehenate.
Film coat
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Not applicable.
ReQuip XL 2mg prolonged-release tablets 2 years.
ReQuip XL 4mg prolonged-release tablets 3 years.
ReQuip XL 8mg prolonged-release tablets 3 years.
Do not store above 25°C. Store in the original package.
PVC/PCTFE/Aluminium or PVC/PCTFE/PVC/Aluminium blister packs.
Packs of 28 or 84 prolonged-release tablets.
Not all pack sizes may be marketed
No special requirements.
SmithKline Beecham plc
Great West Road,
Brentford,
Middlesex TW8 9GS
Trading as:
GlaxoSmithKline UK
Stockley Park West,
Uxbridge,
Middlesex UB11 1BT
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07/05/2008
24/10/2011
