910 Antiparkinsonian Drugs

and 1980 twelve deaths due to orphenadrine were Orphenadrine Citrate Injection; Orphenadrine Citrate, Aspirin, neoplasms in rodents rece1vmg high doses. However, recorded by the UK National Poisons Unit. and Caffeine Tablets. licensed product information states that no cases of uterine 1. Clarke B, et al. Acute poisoning with orphenadrine. Lancet 1985; i: 1386. malignancies have to date been reponed in humans receiving pergolide. The long-term outcome of trearment of Porphyria. The Drug Database for Acute Porphyria, com­ macroprolactinomas with pergolide has been examined in piled by the Norwegian Porphyria Centre (NAPOS) and 23 patients.' and efficacy and relative safety of pergolide was the Porphyria Centre Sweden, classifies orphenadrine as shown after an average of 27 months (range: 9 to 64 porphyrinogenic; it should be prescribed only for compel­ months) treatment. ling reasons and precautions should be taken in all 1. Franks S, et al. Treatment of hyperprolactinaemia with pergolide patients_! mesylate: acute effects and preliminary evaluation of long-term treatment. Lancet 1981; it: 659-61. l. The Drug Database for Acute Porphyria. Available at: http:llwww. 2. Franks S, et al. Effectiveness of pergolide mesylate in long-term drugs·porphyria.org (accessed 30/09111) treatment of hyperprolc!.ctinaemia. BMJ 1983; 286: 1177-9. 3. Kleinberg DL, et al. Pergolide for the treatment of pituitary tumors Withdrawal. A suspected withdrawal syndrome was .secreting prolactin or growth hormone. N Engl J Med 1983; 309: 704-9. 4. et al. reponed in a 56-year-old woman who showed slow neu­ Freda PU, Long-term treatment of prolactin-secreting macro­ adenomas with pergolide. J Clin Endocrinol Metab 2000; 85: 8-13. rological postoperative recovery after her orphenadrine treatment had been stopped abruptly;' her status Parkinsonism. Dopamine agonists such as pergolide are improved when the drug was restaned. often used to begin the treatment of parkinsonism 1. et al. Br J Anaesth Esler MD, Postoperative orphenadrine withdrawal. (p. 889. 1) in an attempt to delay therapy with Ievodopa, 2000; 85: 497. particularly in younger patients. They also have an Pharmacopoeias. In Bur. (see p. vii) and US. adjunctive use when Ievodopa is no longer effective alone Interactions Ph. Eur. 8: (Pergolide Mesilate). A white or ahnost white or cannot be tolerated, and may sometimes be useful in crystalline powder. Slightly soluble in water, in alcohol, and As for antimuscarinics in general (see Atropine Sulfate, reducing 'off' periods with Ievodopa and in ameliorating p. 1312.3). Orphenadrine is an inhibitor of the cytochrome in dichloromethane; very slightly soluble in acetone; other fluctuations in mobility in the later stages of the dis­ P450 isoenzyme CYP2B6, which is involved in the sparingly soluble in methyl alcohol. Protect from light. ease. Pergolide has a relatively long duration of action metabolism of bupropion to its major metabolite; licensed USP 36: (Pergolide Mesylate). A white to off-white powder. compared with other dopamine agonists commonly used. product information advises that orphenadrine should be Slightly soluble in water, in dehydrated alcohol, and in Although the duration of the clinical antiparkinsonian used with caution in patients also receiving bupropion. chloroform; very slightly soluble in acetone; practically effect of pergolide remains to be determined, studies sug­ insoluble in ether; sparingly soluble in methyl alcohol. Store gest it is of the order of 5 to 8 hours. Depending on the Chlorpromazine. For the effect of orphenadrine on plasma in airtight containers. Protect from light. dose used the response to other dopamine agonists in late parkinsonism is to 4 hours for Ievodopa, 2 to 4 hours for concentrations of chlorpromazine, see Antiparkinsonian I lisuride, and 4 to 6 hours for bromocriptine. Drugs, p. I 052.3. Uses and Administration References. Pergolide mesilate, an ergot derivative, is a dopamine D,­ 1. Anonymous. Pergolide (Celance)-a third dopamine agonist. Drug Ther Dextroprapoxyphene. A suggested interaction between agonist with actions and uses similar to those of Bull l991; 29: 79. orphenadrine and dextropropoxyphene was open to ques­ bromocriptine (p. 895.3), but in contrast to bromocriptine 2. Markham A, Benfield P. Pergolide: a review of its pharmacology and tion.1·2 therapeutic use in Parkinson's disease. CNS Druas 1997; 7: 328-40. (a dopamine D,-agonist) it also has agonist propenies at D 3. et al. 1. Pearson RE, Salter FJ. Drug interaction? - orphenadrine with 1 Barone P, Pergolide monotherapy in the treatment of early PD: a and D receptors. Pergolide is used in the management of randomized, controlled study. Neurology 1999; 53: 573-9. propoxyphene. N Eng/ J Med 1970; 282: 1215. 3 4. Clarke CE, Speller J. Pergolide for levodopaRinduced complications in 2. Puckett WH, Visconti JA. Orphenadrine and propoxyphene (cont.). N Parkinson's disease (below) as monotherapy, or as an Engl J Med 1970; 283: 544. adjunct to Ievodopa therapy to reduce 'end-of-dose' or 'on­ Parkinson's disease. Available in The Cochrane Database of Systematic Reviews, Issue 2. Chichester: John Wiley; 1999 (accessed 16102106). off' fluctuations in response; in the UK pergolide is restricted 5. Clarke CE, Speller J. Pergolide versus bromocriptine for levodopa­ Pharmacokinetics to patients who are intolerant of, or who fail to respond to, induced complications in Parkinson's disease. Available in The Cochrane non-ergot drug treatment. Pergolide is given orally as the Database of Systematic Reviews; Issue 2. Chichester: John Wiley; 1999 Orphenadrine is readily absorbed from the gastrointestinal mesilate with doses expressed as the base. Pergolide mesilate (accessed 16/02/06). tract and after intramuscular injection. It is almost 65.3 mg is equivalent to about 50 mg pergolide. Resdess legs syndrome. The aetiology of restless legs completely metabolised to at least 8 metabolites. It is For use as monotherapy an initial dose equivalent to syndrome (see Sleep-associated Movement Disorders, mainly excreted in the urine as metabolites and small 50 micrograms of pergolide is given on the first evening of p. 1034.2) is obscure and treatment has largely been amounts of unchanged drug. The half- life of orphenadrine therapy. The dose is thereafter gradually increased: empirical although dopaminergic therapy has emerged as has been reponed to be 14 hours (but see below). 50 micrograms twice daily is taken on days 2 to 4, then a common first-line choice. Pergolide has produced some increased by 100 to 250 micrograms every 3 or 4 days, given benefit in several studies. 1·6 In a randomised placebo-con­ Half-life. While the mean elimination half-life of orphena­ in 3 divided doses, up to a daily dose of 1.5 mg at day 28. trolled study,6 therapeutic effects were seen with mean drine in 5 healthy subjects given a single dose of the After day 30, the dose should be increased funher by a daily doses of pergolide 400 micrograms after 6 weeks and hydrochloride was found to be 15.5 hours, elimination maximum of 250micrograms twice a week until an maintained after 12 months with doses of up to 720 micr­ half-lives of 30.5 and 40 hours were calculated in 2 optimum response is achieved. Usual maintenance doses ograms daily. patients given repeated oral doses.' are 2.1 to 2.5 mg daily; doses above 3mg daily are not 1. Labout JJM, et al. Difference between single and multiple dose recommended by the EMEA. The daily dose is usually given 1. Silber MH, et al. Pergolide in the management of restless legs syndrome: an extended study. Sleep 1997; 20: 878-82. pharmacokinetics of orphenadrine hydrochloride in man. Bur J Clin in 3 divided doses. Pharmaco/ 1982; 21: 343-50. 2. Winkelmann J, et al. Treatment of restless legs syndrome with For use as adjunctive therapy with Ievodopa, pergolide pergolide-an open clinical trial. Mov Disord 1998; 13: 566-9. should be introduced gradually and during this period 3. Earley CJ, et al. Randomized, double-blind, placebo-controlled trial of Neurology 1998; 51: 1599-1602. patients can have their Ievodopa dosage decreased gradually pergolide in restless legs syndrome. P..�:P.�.��!����---········································································· 4. Wetter TC, et al. A randomized controlled study of pergolide in patients ProprietaryPreparations (details are given in Volume B) until an optimum response is achieved. The initial dose of with restless legs syndrome. NeurokJgy 1999; 52: 944-50. pergolide is the equivalent of 50 micrograms daily for the 5. Stiasny K, et al. Long-term effects of pergolide in the treatment of restless Single-ingredient Preparations. Austral.: Norflex; Canad.: first 2 days, increased gradually by 100 or 150 micrograms legs syndrome. NeurokJgy2001; 56: 1399-1402. Norflex; Orfenace; Chile: Plenactolt; Denm.: Lysantin; Fin.: every third day over the next 12 days of therapy. Further 6. Trenkwalder C, et al. Efficacy of pergolide in treatment of restless legs Norflex; Ger.: Norllex; Gr. : Disipal; Norflex; India: Orpbipa� syndrome: the PEARLS study. Neurology 2004; 62: 1391-7. increases of 250 micrograms may then be made every third Israel: Flexin; Ita!.: Disipal; Malaysia: Norflex; Mex.: Norflex; NZ: Disipal; Norflex; S.Afr.: Disipal; Norflex; Phenerinet; Sin­ day until an optimum response is achieved. A usual ToureHe's syndrome. Pergolide has been studied in the gapore: Onadrine; Swed. : Norflex; Thai.: Norflex; Ofee; Orle­ maintenance dose is 3 mg daily; doses above 3 mg daily are management of Tourette's syndrome (see Tics, p. 1030.1). na!; Phemax; Sinogesic; UK: Biorphen; Disipal; USA: Banllex; not recommended by the EMEA. The daily dose is usually A preliminary study' produced encouraging results, subse­ Flexon; Norflex; Venez. : Norflex. given in 3 divided doses. quently confirmed by placebo-controlled studies in chil­ dren and adolescents.2•3 Multi-ingredient Preparations. Arg.: Belmalen; Flogodisten; Mio Acromegaly. Dopaminergics can produce a paradoxical Aldoron; Mio-Virobron; Austral.: Norgesic; Austria: Neodol· 1. Lipinski JF, et al. Dopamine agonist treatment of Tourette disorder in reduction in growth hormone secretion and may be used Mov Disord 1997; 12: passe; Norgesic; Braz. : Ana-Flex; Biollex; Dalgext; Doralgex; children: results of an open-label trial of pergolide. in the treatment of acromegaly as adjunctive therapy to 402-7. Dorciflext; Dorflex; Doridn; Dorzone; Flexalgex; Flexdor; surgery, radiotherapy, or somatostatin analogues to reduce 2. Gilbert DL, et al. Tourette's syndrome improvement with pergolide in a Miorrelax; Nevralgex; Novralflex; Reflex; Relaflex; Rheumafim; 54: circulating growth hormone levels, although they are less randomized, double-blind, crossover trial. Neurology 2000; 1310-15. Rielex; Royllex; Sedalex; Chile: Norgesict; Cz.: Neodolpasse; 3. Gilbert DL, et al. Tic reduction with pergolide in a randomized controlled effective than somatostatin analogues (p. 1921.1). While Fin.: Dolan; Norgesic; Gr.: Norgesic; Hong Kong: Myodrinet; trial in children. NeurokJgy 2003; 60: 606-11. bromocriptine and cabergoline have been the main Norgesic; Pannus; Hung.: Neodolpasse; , India: Orphamol; Israel: Muscol; Norgesict; Malaysia: Anarex; Cetagesic; Norge­ dopamine agonists used pergolide has also been tried.' Adverse Effectsand Precautions sic; Orphenadol; Paragesic; Sunitont; Mex.: Norflex Plus; Kleinberg DL, et al. Pergolide for the treatment of pituitary tumors NZ: L 309: Norgesic; Philipp.: Norgesic; S.Afr.: Besemax; Besenol; Norflex secreting prolactin or growth hormone. N EnelJ Med 1983; 704-9. As for Bromocriptine, p. 896.3. Co; Uniflex; Singapore: Anarex; Camgesic; Cetagesic; Norgesic; An increased incidence of uterine neoplasms has been Norphen; Ordgesic; Orphenadol; Suniton; Swed.: Norgesic; Hyperprolactinaemia and prolactinomas. Dopamine ago­ reponed in rodentsgiven high doses of pergolide mesilate. Thai.: Cenasic; Corilax; Dorpane; Dysmenic; Fagesict; GPO nists are widely used for the treatment of hyperprolacti­ Gesic; M-Gesic; Medgesic; Muscol; Muscolic; Muslexac; Myo­ naemia secondary to a prolactinoma (p. 2252.2). Pergolide Effects on mental function. For repons of daytime som­ drine; Myollex; Myopa; Myopas; Myosic; Myospa; Mypara has been suggested as an alternative to bromocriptine in nolence occurting in patients receiving dopamine agonists Plus; Nabesac; Neosec; Noraphen; Norgesic; Norgetex; Norgic; this condition. including pergolide, see under Levodopa, p. 905.2. Norphen; Norsica; Nuosic; Nurasic; Orano; Orapa; Orflex; Orge­ Studies'·' of pergolide mesilate in patients with For reference to disturbed behaviour including sic; Omadine; Orpar; Orphengesic; Orphensic; Paradine; Patina; hyperprolactinaemia indicate that single doses reduce excessive gambling reported in patients with Parkinson's Patargesic; Poli-Relaxane; Polydol; Pannus; Pronadrine; Prospa; serum-prolactin concentrations for more than 24 hours. In disease receiving dopamine agonists, see under Levodopa, Relar; Relaxic; Rena; Rexodrin; Togesic; UAB: Muscadol; USA: most patients, the effective dose was between 50 and p. 905.2. Norgesict; Orphenadrine Compound; Orphengesict; Venez. : 150 micrograms daily. Adverse effects were similar to those Norgesic. seen with bromocriptine, although some patients who could Fibrosis. For repons of fibrotic reactions occurting in Pharmocopaeial Preparations not take bromocriptine were able to tolerate pergolide (and patients with Parkinson's disease receiving ergot derivative BP 2014: Orphenadrine Hydrochloride Tablets; vice versa). Pergolide reponedly lost favour for this dopamine agonists including pergolide, see under Adverse USP 36: Orphenadrine Citrate Extended-Release Tablets; indication after repons of an increased incidence of uterine Effects of Bromocriptine, p. 897.3.

All cross-references refer to entries in Volume A 91 1

In Australia, 1 Canada, 2 and Europe3 regulatory autho­ Effects on mental function. For reports of daytime som­ 750 micrograms at weekly intervals to a maximum of 4.5 mg rities recommended that patients undergo a cardiovascular nolence occurring in patients receiving dopamine agonists daily. Modified-release preparations are also available for evaluation before starting treatment with pergolide; including piribedil, see under Adverse Effects of Levodopa, once-daily use. The dosage should be reduced in patients periodic clinical monitoring for development ot valvular p. 905.2. with renal impairment (see below). disease or fibrosis is also recommended. Doses of pergolide For reference to disturbed behaviour including Ifit is necessary to stop pramipexole therapy, it should be above 3 mg daily are not recommended by the EMEA.3 excessive gambling reported in patients with Parkinson's withdrawn gradually. The dose of pramipexole hydro­ Furthermore, use is restricted to patients who are intolerant disease receiving dopamine agonists, see under Adverse chloride should be tapered off at a rate of 7 50 micrograms of, or who fail to respond to, non-ergot drug treatment and Effects of Levodopa, p. 905.2. daily until a daily dose of 750 micrograms has been reached; it is contra-indicated in patients with a history of fibrotic thereafter, the dose should be reduced by 3 7 5 micrograms disorders or in those with anatomical evidence of cardiac Parkinsonism. Piribedil is a dopamine D -agonist while its daily. 2 valvulopathy 4 In 2007, based on further evidence from 2 metabolite is reported to act on D receptors. It has been Pramipexole is also given as a single daily dose, 2 to 3 1 studies, s,6 pergolide was withdrawn from the market in the mainly used as an adjunct to levodopa therapy in the hours before bedtime, in the treatment of restless legs USA7 and Canada 8 treatment of Parkinson's disease (p. 889.1). syndrome. The initial dose of pramipexole hydrochloride is L Adverse Drug Reactions Committee (ADRAC ). Cardiac References. 125 micrograms daily. This may be increased if necessary valvulopathy with pergolide. Drug React Bull 2004; 23: 14. 1. Montastruc JL, et al. Current status of dopamine agonists in Parkinson's after 4 to 7 days to 250micrograms daily. Subsequent doses Also available at: http://www.tga.gov.au/adr/aadrb/aadr0408.pdf ilisease management. Drugs 1993; 46: 384-93. may be increased if necessary by 250micrograms every 4 to (accessed 16/02/06) 2. Montastruc JL, et a!. A randomized, double-blind study of a skin patch of 2. Shire, Canada. New Safety information regarding Permax and 7 days to a maximum of 750 micrograms daily. Response to a dopaminergic agonist, piribedil, in Parkinson's disease. Mov Disord occurrence of cardiac valvulopathy/fibro�is: update on the use of therapy should be evaluated after 3 months; if treatment is 1999; 14: 336-4l. Permax (pergolide mesylate) (issued 12th October, 2004). Available at: 3. Ziegler M, Rondot P. Activite du piribedil dans Ia ma!adie de Parkinson: interrupted for more than a few days, it should be restarted http://www c-sc.gc.ca dhp-mps/ alt_formats/hpfb-dgpsa/pdf/medeff/ .b I etude multicentrique. Presse Med 1999; 28: 1414-18. at 12 5 micrograms daily, and then increased, if required, as shire_permax_2_hpc-cps-eng.pdf (accessed 12/08108) 4. Ziegler M, et a!. Efficacy of piribedil as early combination to levodopa in 3. EMEA. EMEA recommends new warnings and contraindications for described above. For this indication, pramipexole may be patients with stable Parkinson's disease: a 6-month, randomized, ergot-derived dopamine agonists (issued 26th June, 2008). Available at: withdrawn without gradual tapering of the dose. placebo-controlled study. Mov Disord 2003; 18: 418-2 5. http:/I www .cmea. europa .cu /pdh/human/press/pr I 322 39 508en.pdf (accessed 08/08/08) Administration in renal impairment. The elimination of 4. MHRA. Dopamine agonists for Parkinson's disease (issued 30th March, r r i 2007). Available at: http:l/www.mhra.gov.uk/Safetyinformation/ P.. �p�_ c:Ji ?.n.�...... pramipexole is dependent on renal function and the oral Generalsafetyinformationandadvke/Product-specificinformationandad­ ProprietaryPreparations (details are given in Volume B) dosage of pramipexole hydrochloride should therefore be vice/D opamineagonist�forParkinson 1 46sdisease CON20 3 072 9 reduced in patients with renal impairment. I Arg.: Trastoner; Trivastal; Braz.: (accessed 03106108) Single-ingredient Preparations. In the treatment of Parkinson's disease, the following 5. Schade R, et al. Trivastal; China: Trastal Fr. : Trivastal; Ger.: Clarium; regurgitation. Gr.: Trivastal; India: Trivastal;(*!lHt); Ital. : Trivastan; Malaysia: Trivas­ dosage schedule bas been suggested in UK licensed product 6. Zanettini R, et a!. heart di�easc and the use ot dopamine tal; Philipp.: Trivastal; Pol.: Pronoran; Port.: Trivastal; Rus.: information adjusted according to the patient's creatinine N Engl J Med aguni�b for Parkinson's disease. 2007; 356: 39-46. Pronoran (IIpoHopaH); Singapore: Trivastal; Thai.: Trivastal; clearance (CC): 7. FDA. FDA public health advisory: pergolide (marketed as Permax) (IIpoHopau); CC 20 to 50 mL/minute: initially 125 micrograms twice (issued 29th March, 2007). Available at: http:llwww.fda.gov/Drugs/ Turk.: Trivastal; Ukr.: Pronoran Venez. : Trivastal. • DrugSafety/PostmarketDrugSafetyinformationforPatientsandProviders/ daily increased, if necessary, to a maximum of 2.25 mg DrugSafetyJnformationtorHeathcarcProfe<>sionals/PublicHealthAdvi­ daily sories/UCM051285 (accessed 24/08/10) • CC less than 20 mL!minute: initially 125 micrograms 8. Eli lilly, Canada. Health Canada-mandated important safety in­ Pramipexole Hydrochloride once daily increased, if necessary, to a maximum of formation on Pennax {pergolide mesylate) (issued J Oth August, (BANM, r!NNM) 2007). Available at: http://www.lilly.ca/servlets/sfs;jsessionid= 1.5mg daily 9EOE83CA662673A89F439C68DAA3AC4B?t=/documentManagerl Hldreiddrurb , de \pramtpe�ol; �NU:98528:E; ·. Pramipexol, Similar reductions are suggested in US licensed information sfdoc.file.supply&e=UTF-8b-i= 123 3164 7 68976&l=O&s=S62tYO HmUj ­ hidroc!oruio.de; ramipexole, Chlorhydra(e ge; Pramipexole, for patients with a CC of 30 to 50 mL/minute and 15 to less qiTRlfa&filelD=125ll3847237l$ (accessed 23/08/10) � dich!Orh}((lra>e . Dihydrochlpride than 30 mL/minute, respectively; no recommendation is l'ramtr:rexoli dfhyQtJJde;: Praniipexole(!'!Ioridum:. Pramip_exoli Hydroch!ori­{USAN); made for those with a CC of less than 15 mL!minute. ··· If renal function declines during maintenance therapy it Interactions (pramipexole hydrochloride); _ is recommended that the daily dose of pramipexole should As for Bromocriptine, p. 899.1. dum,(prarr\tpexote);.SNIJd}Y9-(;blY·flpaMI1 neKcoi13 5UD- be reduced by the same percentage as the decline in CC. {S)-2"Amlnb-4,5.,6,7-tetlahydi.o;Ej..(propr ylamino)benzmhfa­ 919Y· V\!1POX1lop0A. Lower doses are used in the treatment of restless legs zole dihydroc!)loride monohydrate. Pharmacokinetics syndrome and UK licensed information considers dosage reductions unnecessary in patients with CC of more than Pergolide mesilate is absorbed from the gastrointestinal CioH.J,N35,2HCL H;,0�3023 (a nhydrous tract. It is reported to be about 90% bound to plasma ....:: 1046J2 ·2ti-Dc 20mL/minute. US licensed information recommends that pramOl.S ipexp/e lpran)i[i(!�191211lei;'81·9 104632-25�9 (p ramipexole hydro· proteins. It is excreted mainly in the urine in the form of o the interval between titration steps is increased to 14 days in metabolites. /JydrochiQricf.ej; those patients with CC of 20 to 60 mL/minute. Ach lor/if.e monohydrate). References. TC..;,.N04BCOS. Parkinsonism. Pramipexole is a dopamine agonist used in I. Curr Ve t ....:: Blin 0. The pharmacokinetics of pergolide in Parkinson's disease. Opin Neuro ATC ON04BC05. the treatment of Parkinson's disease (p. 889.1) as an / 2003; 16 (suppl l): S9-Sl2. �•]DB67NP06J · .. UN/! adjunct to levodopa therapy to reduce 'off' periods with Pharmacopoeias. In Bur. (see p. vii) and US. levodopa and ameliorate other fluctuations of mobility in Ph. Eur. 8: (Pramipexole Dihydrochloride Monohydrate). A the later stages of the disease. It is also used as monother­ ProprietaryPreparations (details are given in Volume B) white or almost white, crystalline powder. Freely soluble in apy early in the course of the disease in an attempt to water; sparingly soluble to slightly soluble in alcohol; delay therapy with levodopa. Arg.: Aroltex; Celance; Geranil; Single·ingredient Preparations. soluble in methyl alcohol; practically insoluble in Austral.: Permax; Austria: Permax; Be/g. : Permax; Braz.: References. dichloromethane. pH of a 2% solution in water is 2.8 to 3.4. Celancet; Cz.: Permax; Fr.: Celancet; Ger.: Parkotilt; Gr.: l. Parkinson Study Group. Safety and efficacy of pramipexole in early Parkinson disease: a randomized dose-ranging study. JAMA 1997; 278: Celancet; Irl.: Celance; Ita'- : Nopar; Mex. : Permax; Neth.: Per� USP 36: (Pramipexole Dihydrochloride). A white to almost 125-30. maxt; NZ: Permax; Port.: Permax; S.Afr. : Pennaxt; Singapore: white crystalline powder. Freely soluble in water; slightly 2. Lieberman A, et a!. Clinical evaluation of pramipcxole in advanced Celance; Spain: Pharkent; Switz.: Permaxt; Turk.: Permax; soluble in alcohol; soluble in methyl alcohol; practically Parkinson's disease: results of a double-blind, placebo-controlled, UK: Celancet. insoluble in dichloromethane. Protect from moisture and parallel-group 1997; 49: 162-8. light. 3. Shannon KM, a novel dopamine agonist, Pharmacopoeial Preparations as monotherapy in mild to moderate Parkinson's disease. Neurology USP 36: Pergolide Tablets. 1997; 49: 724-8. Uses and Administration 4. Guttman M. International Pramipexole-Bromocriptine Study Group. Double-blind comparison of pramipexole and bromocriptine treatment Pramipexole is a non-ergot dopamine agonist with actions with placebo in advanc.ed Parkinson'� disease. Neurology 1997; 49: 1060-- Piribedil (r!NN) similar to those of bromocriptine (p. 895.3). It is used ' 5. 5. Parkinson Study Group. Pramipexolc vs levodopa as initial treatment for similarly in the management of Parkinson's disease (below), Parkinson disease: a randomized controlled trial. lAMA 2000; 284: either alone or as an adjunct to levodopa therapy to reduce 1931-8. 'end-of-dose' or 'on-off' fluctuations in response. Prami­ 6. Clarke CE, et al. Pramipexole for levodopa-induced complications in pexole is also used for the treatment of nwderate to severe Parkinson's disease. Available in The Cochrane Database of Systematic Reviews; Issue 2. Chichester: John Wiley; 2000 (accessed 16102106). restless legs syndrome (below). It is given orally as the 7. Clarke CE, eta!. Pramipexole versus bromocriptine for levodopa-induced bydrochloride; doses have been described in terms of the complications in Parkinson's dbease. Available in The Cochrane Va --· hydrochloride (as below) or of the base. In terms of Database of Systematic Reviews; ls<;ue 2. Chichester: John Wiley; 2000 ATC ON04BC08. equivalency: (accessed 16102/06). UNN 00221<' PRDJ. 8. Parkinson Study Group. Pramipexole vs levodopa as initial treatment for pramipexole hydrochloride 125 micrograms is equiva­ Parkinson disease: a 4-year randomized controlled trial. Arch Neurol lent to about 88 micrograms of pramipexole 2004; 61: 1044-53. Corre(_1ion. ibid. 2005; 62: 430. Profile 9. Moller JC, et al. Long-term efficacy and <;afety of pramipexole in • pramipexole hydrochloride 2 50 micrograms is equiva­ Piribedil is a non -ergot dopamine agonist that has been lent to about 180 micrograms of pramipexole advanced Parkinson's disease: results from a European multicenter trial. Mov Disord 2005; 20: 602-10. given orally in the treatment of parkinsonism (below) and • pramipexole hydrochloride 500 micrograms is equiva­ in circulatory disorders. Piribedil mesilate has been given by lent to about 3 50 micrograms of pramipexole Restless legs syndrome. The aetiology of restless legs injection for circulatory disorders. Preparations of piribedil pramipexole hydrochloride I mg is equivalent to about • syndrome (RLS-see Sleep-associated Movement Disor­ are licensed in some countries for the manage1nent of 700 micrograms of pramipexole ders, p. 1034.2) is obscure and treatment has largely been impaired memory and cognitive function in the elderly. In the treatment of Parkinson's disease, the dose of empirical, although dopaminergic therapy has emerged as Adverse effects reported include nausea and vomiting, pramipexole should be increased gradually and the dose of a common first-line choice. Low-dose pramipexole has dizziness, hallucinations, confusion, drowsiness, hypo­ levodopa gradually reduced during the dose-titration and produced some benefit in several studies1-8 and is licensed thermia, dyskinesias, and occasional changes in liver maintenance phases until an optimum response is achieved. 1 for the treatment of moderate to severe RLS in some function. The initial dose of pramipexole hydrochloride is 125 micr­ countries. When used as monotherapy in Parkinson's disease a ograms three times daily increased to 250 micrograms three I. et a!. usual daily oral dose of piribedil is 150 to 250 mg in divided times daily in the second week and then to 500 micrograms Lin S-C, syndrome. Mayo doses; a daily dose of 80 to 140 mg may be suitable when three times daily in the third week according to response. 2. Montplabir J, et al. Restless legs syndrome improved by pramipexole: a used as an adjunct to levodopa. Thereafter the daily dose may be increased if necessary by double-blind randomized trial. Neurology 1999; 52: 938-4"3.

The symbol denotes a preparation no longer actively marketed t