Mesilote 895
Antidepressants. A report1 of 5 patients who developed Biperiden is used in the symptomatic treatment of Profile delirium while taking an antipsychotic, an SSRI, and ben parkinsonism (p. 889.1 ), including the alleviation of the zatropine suggested that there might be an interaction extrapyramidal syndrome induced by drugs such as Bornaprine hydrochloride is a quaternary ammonium between SSRis and benzatropine. phenothiazines, but, like other antimuscarinics, is of no antimuscarinic with actions and uses similar to those of I. Roth A, et al. Delirium associated with the combination of a neuroleptic, value against tardive dyskinesias. trihexyphenidyl (p. 917.3). It is used in the 'ymptomatic an SSRI. and benztropine. J Clin Psychiatry 1994; 55: 492-5. Biperiden is given orally as the hydrochloride and by treatment of parkinsonism (p. 889.1), including the injection as the lactate; doses are expressed in terms of the alleviation of the extrapyramidal syndrome induced by Antipsychalics. Fatal heat stroke after exposure to an relevant salt. drugs such as phenothiazines, but, like other antirnusca ambient temperature of over 29 degrees has been US licensed product information gives the initial oral rinics, is of no value against tardive dyskinesias; it is claimed reportedt2 in patients receiving benzatropine with dose for Parkinson's disease as 2 mg of the hydrochloride to be mainly effective against tremor. Bomaprine hydro antipsychotics. Paralytic ileus, sometimes fatal, has also 3 or 4 times daily which can then be increased according to chloride is given orally in initial doses of 2 mg daily been seen in patients taking benzatropine with antipsy response to a maximum of l6mg daily. In some countries a gradually increased to 6 to 12 mg daily according to chotics.3 much lower initial oral dose of I mg twice daily is response. It is also used in the treatment of hyperhidrosis Can Med Assoc J recommended. In the USA the recommended oral dose for (p. 1685.1) in a dose of 4 to Smg daily. l. Stadnyk AN. Glezos JD. Drug-induced heat stroke. 1983; 128: 957-9. drug-induced extrapyramidal symptoms is 2 mg of the 2. Tyndel F, Labonte R. Drug-facilitated heat stroke. Can Med Assoc J 1983; P epa a ons hydrochloride 1 to 3 times daily. In other countries a wider r .r ti 129: 680...... ! dose range of I to 4mg I to 4 times daily is used. Modified 3. Wade LC, Ellenor GL Combination mesoridazine- and benztropine ProprietaryPreparations (details are given in Volume B) mesylate-induced paralytic ileus: two case reports. Drug Intel! Clin Pharm release tablets with different dose schedules are available in Austria: Sormodren; Ger.: Sor 1980; 14: 17�22. some countries. Single-ingredient Preparations. modren; Gr. : Sormodren; Ital. : Sormodren; Turk.: Sormodren. In severe cases, or when biperiden cannot be given orally, the lactate can be given by intramuscular or slow r i i P.r.�P.
increased to 2 to 2.5 mg at night after 2 to 3 days, and Hepatic encephalopathy. For the view that the evidence 2. Anonymous. Cyclical breast pain-what works and what doesn't. Drug l Ther Bull 1992; 30: 1-3. subsequently increased by to 2.5 mg every 2 to 3 days to a does not support the use of dopaminergics such as bromo 3. Pye JK, et al. Clinical experience of drug treatments for mastalgia. Lancet dose of 2.5 mg twice daily, or more if necessary. In the USA. criptine in the management of hepatic encephalopathy see 1985; ii: 373-7. 4. a usual starting dose is !.25 to 2.5 mg daily increased by p. 181!.2. Mansel RE, Dogliotti L. European multicentre trial of bromocriptine in 2.5 mg every 2 to 7 days. cyclical mastalgia. Lancet 1990; 335: 190-3. In the treatment of hypogonadism and galacto Hyperprolactinaemia and prolactinomas. Prolactinomas Bromocriptine has rrhoea syndromes and infertility bromocriptine is (prolactin-secreting pituitary adenomas) are among the Neuroleptic malignant syndrome. introduced gradually as described above. Most patients with commonest causes of hyperprolactinaemia. Raised serum been used in doses of up to 30 mg daily, 1·6 usually alone hyperprolactinaemia respond to 7.5 mg daily but up to prolactin concentrations can result in reduced gonadotro or with dantrolene, in the treatment of neuroleptic malig 30 mg daily may be required. Infertile patients without phin production, which in turn may suppress gonadal nant syndrome (p. !050.2) although some workers have raised serum concentrations of prolactin are usually given function. Consequences may include oligomenorrhoea or not found it to be of use.7 2.5 mg twice daily. In patients known to have prolactino amenorrhoea, and infertility in either sex. Galactorrhoea 1. Mueller PS, etal. Neuroleptic malignant syndrome: successful treatment mas the dose is also introduced gradually as described above with bromocriptine. JAMA 1983; 249: 386-8. may also result from high prolactin levels and can occur in 2. Dhib-Jalbut S, et al. Treatment of the neuroleptic malignant syndrome and may then be increased further by 2.5 mg every 2 to 3 men as well as women. With bromocriptine. lAMA 1983; 250: 484--5. days to a dose of 5 mg every 6 hours but occasionally Dopamine is the major inhibitory factor in the 3. Clarke CE, et a!. Clinical spectrum of neuroleptic malignant syndrome. patients may require up to 30 mg daily. Although hypothalamus and directly inhibits the secretion of Lancet 1988; ii: 969-70. unlicensed in the and USA, bromocriptine is used in 4. Guerrero RM, Shifrar KA. Diagnosis and treatment of neuroleptic prolactin. Bromocriptine, a dopamine agonist, has been malignant syndrome. Clin Pharm 1988; 7: 697-701. some countries for UKcyclical benign breast and menstrual the first choice of treatment in many centres for the 5. Lo TCM, et a!. Neuroleptic malignant syndrome: another medical cause disorders. In benign breast disease bromocriptine is treatment of hyperprolactinaemia secondary to a pro of acute abdomen. Postgrad Med J 1989; 65: 653-5. introduced gradually up to a daily dosage of 5 to 7.5 mg if lactinoma although cabergoline is now preferred by some. 6. Chandran GJ, et al. Neuroleptic malignant syndrome: case report and necessary. In the treatment of premenstrual symptoms discussion. Can Med Assoc J 2003; 169: 439-42. Bromocriptine is extremely effective in controlling elevated 7. Rosebush PI, et al. The treatment of neuroleptic malignant syndrome: therapy should begin on day 14 of the cycle and introduced circulating prolactin concentrations and restoring gonadal are dantrolene and bromocriptine useful adjuncts to supportive care? Br gradually up to a usual dosage of 2.5 mg twice daily until function; although it is rarely curative, it may produce J Psychiatry 1991; 159: 709-12. menstruation begins. considerable shrinkage of the adenoma.1 Bromocriptine may be used as an adjunct to surgery and The sensitivity of hyperprolactinaemia to bromocriptine Parkinsonism. Dopamine agonists such as bromocriptine radiotherapy to reduce plasma-growth hormone concentra therapy can vary considerably between patients and this is are often used to be in treatment of parkinsonism tions in acromegalic patients. In the UK, it is introduced reflected in the wide range of oral doses required to reduce (p. 889.1 ), particularly ing younger patients, in an attempt gradually as described above and may then be increased prolactin concentrations to normal levels. Although to delay therapy with levodopa. They also have an adjunc further by 2.5 mg every 2 to 3 days if necessary up to 5 mg beginning therapy with gradually increasing doses can tive use when levodopa is no longer effective alone or every 6 hours, according to response. In the USA, the usual minimise adverse effects it has been reported that about 5 to cannot be tolerated and may sometimes be useful in redu starting dose (see above) may be increased by !.25 to 2.5 mg 10% of patients are unable to tolerate oral bromocriptine;2 cing 'off' periods with levodopa and in ameliorating other every 3 to 7 days to a maximum daily dose of 100 mg if other dosage routes have therefore been investigated. fluctuations of mobility in the later stage of the disease. necessary; the usual dosage range is 20 to 30 mg daily. Bromocriptine is well absorbed from standard oral tablets However, in early disease, there is no evidence that In Parkinson's disease bromocriptine has been used placed in the vagina and appears to be both effective in adjunctive bromocriptine prevents or delays the onset of alone, although it is usually given as an adjunct to levodopa lowering prolactin concentrations and well tolerated when motor complications associated with levodopa monother treatment. It should be introduced even more gradually given by this route. 3 However, limitations are considered to apy. than the regimen above, and during this period patients be the relatively short duration of action and the relatively already receiving levodopa can have their levodopa dosage References. low dose that can be given. 2 A depot preparation given 1. Temlett JA, et a!. Adjunctive therapy with bromocriptine in Parkinson's decreased gradually until an optimal response is achieved. intramuscularly in a dose of 50 to 250 mg monthly has been disease. S Afr Med J 1990; 78: 680-5. In the a suggested initial dose is the equivalent of 1 to et a!. UK, found to be effective and well tolerated in long-term 2. Rely , The Sydney Multicentre Study of Parkinson's disease: a 1.25 mg of bromocriptine at night during week l, increased studies;4•5 it is reported to be used in some centres to begin randomised,l\1A prospective five year study comparing low dose bromo to 2 to 2.5 mg at night for week 2, 2.5 mg twice daily for criptine with low dose levodopa-carbidopa. J Neurol Neurosurg Psychiatry treatment for macroprolactinomas. 2 1994; 57: 903-10. week 3, and for week 4, 2.5 mg three tlmes daily; the dose For discussions of the management of hyperprolactinae 3. Montastruc JL, et al. A randomised controlled study comparing may be increased thereafter by 2.5 mg every 3 to 14 days mia and associated disorders see p. 2252.2 (hyperprolacti bromocriptine to which levodopa was later added, with levodopa alone according to response. The EMEA has recommended a naemia), p. 225!.3 (amenorrhoea), p. 2252.3 (hypogonad in previously untreated patients with Parkinson's disease: a five year maximum dose of 30 mg daily. In the USA, a usual starting follow up. J Neurol Neurosurg Psychiatry 1994; 57: 1034--8. ism), p. 2348.2 (erectile dysfunction), and p. 2253.1 4. Gimene7.-Rold
All cross-references refer to entries in Volume A Mesilate 897
Adverse effects are generally dose-related and may • Although a causal relationship between the use of insomnia and 4 had received doses only previously asso therefore be more frequent with the higher doses that have bromocriptine and these adverse effects in postpartum ciated with psychosis in susceptible patients 9 been used in the treatment of parkinsonism and women has not been established, licensed product For reference to disturbed behaviom including acromegaly. Reduction of the dosage, followed in a few information recommends that bromocriptine should not excessive gambling reported in patients with Parkinson's days by a more gradual increase, may alleviate many be used post partum or in the puerperium in women disease receiving dopamine agonists, see under Levodopa, adverse effects. Nausea may be reduced by taking with high blood pressure, coronary artery disease or p. 905.2. bromocriptine with food; domperidone may also be given other severe cardiovascular disorders, or symptoms or For repons of daytime somnolence occurring in at least I hour before bromocriptine, for the first few days of history of serious psychiatric disorders. patients receiving dopamine agonists including bromo therapy. • It is also recommended that when bromocriptine is used criptine, see under Levodopa, p. 905.2. Bromocriptine and similar drugs are vasoconstrictors; in postpanum women blood pressure should be carefully l. Caine DB, et al. Long-term treatment of parkinsonism with Lancet 1978; 735-7. Raynaud's syndrome or digital vasospasm, induced by cold, monitored, especially during the first few days and if bromocriptine. i: and leg cramps have been reponed. Other cardiovascular hypenension, unremitting headache, or signs of CNS 2. Vlissides DN, et a!. Bromocriptine-induced mania? BMJ 1978; 1: 510. 3. Brook NM, Cookson lB . Bromocriptine-induced mania? BMJ 1978; 1: effects have included erythromelalgia, prolonged severe toxicity develop, treatment should be discontinued 790. hypotension, arrhythmias, and exacerbation of angina. immediately. 4. Pearce I, Pearce JMS. Bromocriptine in parkinsonism. BMJ 1978; 1: Very rarely hypertension, myocardial infarction, seizures or Severe dilated cardiomyopathy has been reponed in a 1402-4. stroke (both sometimes preceded by severe headache or patient being treated with bromocriptine for microprolacti 5. Pearson KC. Mental disorders from low-dose bromocriptine. N Eng! J Med 1981; 305: 173. visual disturbances), and psychiatric disorders have been noma.7 6. Le Femrre CM, et a!. Bromocriptine-induced psychosis in acromegaly. reported in postpartum women given bromocriptine. For details of fibrotic reactions resulting in cardiovas BMJ 1982; 285: 1315. The use of ergot derivatives such as bromocriptine has cular adverse effects, see Fibrosis, below. 7. Procter AW, et al. Bromocriptine induced psychosis in acromegaly. BMJ 1983; 286: 50. Correction. ibid.; 311. been associated with retroperitoneal fibrosis, pleural 1. Parkes D. Side effects of bromocriptine. N Eng! J Med 1980; 302: 749-50. i 8. 2. Einarson TR, Turchet EN. Psychotic reaction to low-dose bromocriptine. thickening and effusions, and pericarditis and pericardia! Anonymous. Postpartum hypertension, seizures, strokes reported with Clin Pharm 1983; 2: 273--4. bromocriptine. FDA Drug Bull 1984; 14: 3. effusions. 9. Turner et a!. Psychotic reactions during treatment of pituitary 3. Ruch A, Duhring JL Postpartum myocardial infarction in a patient TH, tumours with dopamine agonists. BMJ 1984; 289: llOl-3. Other adverse effects reported include headache, nasal receiving bromocriptine. Obstet Gyneco/ 1989; 74: 448-5 1. congestion, drowsiness, dry mouth, constipation, diarrhoea, 4. Larrazet F, et al. Possible bromocriptine-induced myocardial infarction. and altered liver-function tests. Dyskinesias and psycho Ann Intern Med 1993; ll8: 199-200. Effectson the nervous system. CSF rhinorrhoea has been motor excitation have occurred in patients suffering from 5. Watson DL, et al. Bromocriptine mesylate for lactation suppression: a associated with bromocriptine therapy in patients with risk for postpartum hypertension? Obstet Gynecol 1989; 74: 573�6. invasive prolactinomas. A report of 3 cases found 13 parkinsonism. Gastrointestinal bleeding has been reponed 6. et al. Epidemiology Rothman KJ, Bromocriptine and puerperal seizures. in acromegalic patients. Psychosis, with hallucinations, 1990; 1: 232-8. further cases on reviewing the literature; 1 of these, 7 delusions, and confusion, occurs panicularly when high 7. Kaushik P, et al. Acute onset of severe dilated cardiomyopathy during patients had developed rhinorrhoea within I month of doses are used to treat parkinsonism, but has also been bromocriptine therapy. Ann Pharmacother 2004; 38: 1219-2 1. staning bromocriptine and 2 cases developed after 12 reported with low doses. A neuroleptic malignant-lllre months. syndrome associated with abrupt withdrawal of bromo Effectson the ears. Audiometric evidence of bilateral sen For reference to seizures associated with the use of criptine has been reported very rarely. sorineural hearing loss was reported in 3 patients receiving bromocriptine in postpartum women, see Effects on the bromocriptine 15 or 20 mg daily for chronic hepatic Cardiovascular System, above. Incidence of adverse effects. In 27 published studies of encephalopathy.1 Hearing improved when the dose was 1. Barlas 0, et al. Bromocriptine-induced cerebrospinal fluid fistula in the treatment of Parkinson's disease, 217 of the 790 reduced to mg daily. patients with macroprolactinomas: report of three cases and a review of 10 the literature. Surg Neurol l994; 41: 486-9. patients given bromocriptine had adverse effects.1 Mental I. Lanthier PL, et al. Bromocriptine-associated ototoxicity. J LaryngolOtol changes were noted in 90 patients, dyskinesia in 20, 1984; 98: 399-404. Effects on the respiratory system. For repons of fibrotic onhostatic hypotension in 40, and gastrointestinal effects reactions occurring in patients with Parkinson's disease in 40. The fewest adverse effects (9%) occurred with low Effectson electrolytes. There have been isolated reports of receiving ergot derivative dopamine agonists including dose bromocriptine, more occurred with high-dose bromo severe hyponatraemia associated with the use of bromo bromocriptine, see Fibrosis, below. criptine (27%) or with low-dose bromocriptine with leva criptine.u dopa (26% ), and the most occurred with high-dose 1. Marshall AW, et a!. Bromocriptine-associated hyponatraemia in Effects on sexual function. For repons of the effects of bromocriptine and levodopa (32%). However, those on cirrhosis. BMJ 1982; 285: 1534-5. dopamine agonists on sexual function, see under Levo high doses had more advanced disease and might have 2. Damase-Michel C, et a!. Hyponatraemia in a patient treated with dopa, p. 906.1. been more susceptible to mental changes and dyskinesias. bromocriptine. Drug Invest 1993; 5: 285-7. An analysis by the manufacturer of published repons on Effects on the urinary tract. Constant dribbling urinary patients treated with bromocriptine for I to I 0 years Effects on the eyes. Blurred vision and diplopia have been incontinence developed in a woman receiving bromo concluded that in general, adverse effects noted were no reported in several patients receiving bromocriptine. 1 ctiptine 2. mg daily for a recurrent pituitary growth; different from those associated with shan-term treatment 2 5 Reversible myopia also developed in a patient with hyper symptoms resolved on stopping the drug and recurred on 1. Lieberman AN, Goldstein M. Bromocriptine in Parkinson disease. prolactinaemia given bromocriptine. 2 rechallenge.1 Bromocriptine has been shown to have two Pharmacal Rev 1985; 37: 217�27. Licensed product information states that visual field 2. effects, one on the bladder outflow tract and one on the Wei! C. The safety of bromocriptine in long-term use: a review of the impairment associated with macroprolactinoma usually literature. Curr Med Res Opin 1986; 10: 25�51. detrusor muscle, that could predispose to urinary incont resolves with bromocriptine treatment. However, in a inence.2 patient with progressive visual loss due to compression of Effects on the blood. Severe leucopenia and mild throm 1. MA Sandyk R, Gillman . Urinary incontinence in patient on long-term the optic chiasm by a large pituitary tumour, bromocriptine Lancet 1983; l26D-l. bocytopenia developed in a 23-year-old woman after bromocriptine. ii: caused total visual loss within hours. 3 Vision slowly 2. Lancet 1984; 228. treatment with bromocriptine 7. 5 to I 0 mg daily for about Caine M. Bromocriptine and urinary incontinence. i: 3 months.1 returned to normal when the patient was placed in the supine position; the most likely cause of the visual loss was Fibrosis. Fibrosis has been associated with the long-term I. Giampietro 0,et at. Severe leukopenia and mild thrombocytopenia after chronic bromocriptine (CB-154) administration. Am J Med Sd 1981; thought to be orthostatic hypotension with resultant use of ergot derivatives (see under Methysergide, 281: 169-72. decrease in perfusion pressure to the visual system. p. 677.2). Fibrotic reactions such as cardiac valvulopathy Monitoring of visual fields is recommended in patients with and pleuropulmonary effusion have been reported with Effects on the cardiovascular system. An early review macroprolactinoma. bromocriptine, cabergoline, lisuride, and pergolide therapy noted that asymptomatic hypotension occurred in many Bromocriptine has been reported to cause visual cortical in patients with Parkinson's disease. subjects given bromocriptine.1 However, faintness and diz disturbances.4 In some cases blurred vision and transient Constrictive pericarditis1 was reported in 2 patients who ziness, sometimes accompanied by nausea and vomiting, conical blindness have preceded seizures and strokes. had received bromocriptine for 2 and 4 years, respectively; were common at the start of treatment with bromocriptine l. Caine DB, et a!. long-term treatment of parkinsonism with the latter still had slight pleural effusion 13 months after the Lancet 1978; 735-7. and these symptoms rather than an anaphylactic type of bromocriptine. i: drug was stopped. Valvular hean disease2 developed in 2. et a!. Lancet 1981; reaction were likely to account for the collapse that Manor RS, Myopia during bromocriptine treatment. i: another patient who had received bromocriptine for 5 years; 102. occurred in a few sensitive patients. Two of 53 patients 3. WT symptoms resolved 6 months after stopping the drug. Couldwell , Weiss MH. Visual loss associated with bromocriptine. with Parkinson's disease fainted after an initial dose of Lancet 1992; 340: 1410-11. Interstitial lung disease, with dyspnoea, chest pain, cough, 1.25 or 2.5 mg, but the exact incidence of shock-like syn 4. Lane RJM, Routledge PA. Drug-induced neurological disorders. Drugs and pulmonary fibrosis was reported3 in a patient after use dromes was difficult to assess; the manufacturers had sta 1983; 26: 124-47. of relatively high doses of bromocriptine (62 mg daily). ted that 22 of over 10 000 subjects given bromocriptine Respiratory symptoms largely resolved onwithdrawal ofthe had had hypotension and collapse, mainly at the start of Effects on mental function. High doses of bromocriptine drug, although functional respiratory changes and treatment. are well known to cause psychotic reactions in patients moderate dyspnoea persisted after 6 months. A review of • All patients staning treatment should be warned of the with parkinsonism. 1 However, mania has also been asso the literature revealed several other repons of pleuro possibility of fainting. The initial dose should not exceed ciated with the use of bromocriptine post panum2•3 and it pulmonary fibrosis associated with relatively high doses of 1.25 to 2.5 mg and should be taken with food and in bed. has been stated that psychological symptoms can occur bromocriptine which occurred after between 15 days and If fainting does occur recovery is usually rapid and with doses of only 2.5 to 5mg daily 4 It was also noted up to 3 years of treatment. Although the incidence of this spontaneous. Tolerance to adverse effects such as hypo that, unlike the relatively mild and transient symptoms effect did not seem to be high, similar cases have continued tension and nausea may develop rapidly. associated with levodopa, bromocriptine produces a severe to be reponed 4·6 In June 2008 the EMEA recommended Hypertension, seizures, stroke, and myocardial infarction have psychosis in which the patient is violent and aggressive, that for long-term use in conditions such as Parkinson's been associated with bromocriptine therapy, notably in suffering from intense delusions which are often hostile disease, the maximum dose should be 30mg daily.' postpartum women.2-4 A study involving 1813 women and violent; complete withdrawal of bromocriptine may A patient developed pleuropulmonary disease 16 months suggested that the risk of postpartum hypertension was still leave a residue of severe psychotic illness persisting after starting treatment with cabergoline;8 he had previously increased in women who had pregnancy-induced hyper for I to 3 weeks. Psychosis associated with low doses of received bromocriptine for I 0 years and had had a normal tension and that this risk was further increased in those who bromocriptine has often occurred in patients with a his chest X-ray at the time of transfer to cabergoline treatment. took bromocriptine for suppression of lactation. 5 A case tory of psychotic illness or disturbances in behaviour and In another repon, 2 cases of pleural effusion/puimonary controlled study6 involving 43 of the women who had had mood.5-7 Drug-related psychotic reactions have also been fibrosis, occurring after I 0 to ll months of treatment, were postpartum seizures while taking bromocriptine found that reponed in patients with no psychiatric history;8-9 of 600 described -' One patient had modest pretreatment lung while the initial risk of seizures appeared to be lower in patients given bromocriptine or lisuride for the treatment alterations attributed to previous bromocriptine therapy. patients taking bromocriptine there was a small positive of acromegaly or prolactinoma, 8 developed symptoms Withdrawal was associated with improvement in both cases. association with seizures occurring more than 72 hours after including anxiety, depression, auditory hallucinations, Congestive heart failure secondary to constrictive pericard delivery. delusions, hyperactivity, disinhibition, euphoria, and itis, and severe pleuropulmonary fibrosis that resulted in 898
dyspnoea, persistent in one case, 10 have also been reported 15. CSM/MHRA. Pergolide (Celance) and cardiac valvulopathy. Current in patients with hypersensitivity to bromocriptine or other Problems in 2 patients receiving long-term cabergoline. 10•11 Another 2003; 29: 7. Also available at: http://www.mhra.gov.uk/home/ ergot alkaloids, and in those with uncontrolled hyper idcplg?IdcService=GET_FILE&dDocName=CON007450&RevisionSelec patient developed cardiac valvulopathy after taking tionMethod=LatestReleased (accessed 16/02/06) tension. 16. Pritchett AM et a!. Valvular heart disease in patients taking pergolide. cabergoline for a total of 20 months;12 her dosage was , Bromocriptine is contra-indicated in the toxaemia of 4 mg daily for the last 7 months. Cardiac symptoms slowly Mayo Clin Proc 2002; 77: 1280-6. pregnancy. It should also not be used postpartum or in the et al. improved on withdrawal of the drug, although some 17. Flowers CM, The US Food and Drug Administration's registry of puerperium in women with hypertension, coronary artery patients with pergolide-associated valvular heart disease. MayoClin Proc evidence of valvular defects was still present 23 months 2003; 78: 730-l. disease, or symptoms or a history of serious psychiatric later. Valvular heart disease has also been reported in a 74- 18. Van Camp G, et al. Treatment of Parkinson's disease with pergolide and disorders. When used, blood pressure should be monitored year-old man after 4 months of therapy with cabergoline relation to restrictive valvular heart disease. Lancet 2004; 363: 1179-83. carefully, especially during the first few days in postpartum 19. Agarwal P, et al. Diagnosis and management of pergolide-induced women. Particular caution is necessary in patients who are [dosage not stated] 13 By December 2005, 86 cases of fibrosis. Mov Disord 2004; 19: 699-704. suspected adverse reactions to cabergoline had been 20. Simcock D, Paviour D. Rapid onset of pergolide-induced pulmonary receiving or who have recently received drugs that can alter reported to the Australian Drug Reactions Advisory fibrosis in a patient with corticobasal degeneration. Hosp Med 2004; 65: blood pressure; use with ergot alkaloids during the Committee (ADRAC),14 of which 15 described pleural or 372-3. puerperium is not recommended. Treatment in postpartum et at. 21. Tintner R, Pleuropulmonary fibrosis after long-term treatment with women should be stopped hnmediately if hypertension, pulmonary fibrosis/effusion, or pneumonitis; time to onset the dopamine agonist pergolide for Parkinson disease. Arch Neurol 2005; ranged from a few days to over 3 years with a median of 4 62: 1290-5. unremitting headache, or signs of CNS toxicity develop. months. There had been no reports of fibrotic complications 22. CSM/MCA. Fibrotic reactions with pergolide and other ergot-derived Hypotensive reactions may be disturbing in some associated with low-dose cabergoline in the treatment of receptor agonists. Current Problems 2002; 28: 3. Also available at: http:// patients during the first few days of treatment and those www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE&dDocName= who drive or operate machinery should be warned of the lactation suppression and hyperprolactinaemia. The UK CON007454&RevisionSelectionMethod=LatestReleased (accessed MHRA considers the risk of cardiac valvulopathy to be high 16/02/06) possibility of dizziness and fainting during this period. and UK labelling for cabergoline has been amended Excessive daytime sleepiness and sudden onset of sleep may accordingly (see p. 900.2) with the EMEA in June 2008 Hypersensitivity. An allergic reaction developed in a 26- also occur with bromocriptine and other dopaminergic recommending a maximum dose of 3 mg daily.7 year-old woman being treated with bromocriptine for a agonists, and caution is advised when driving or operating A woman developed bilateral pleural effusions after prolactin -secreting microadenoma.1 The patient reacted machinery; patients who suffer such effects should not drive taking lisuride 4mg daily for about 17 months 8 Her similarly to lisuride and treatment was continued with or operate machinery until the effects have stopped condition improved on stopping lisuride. quinagolide. recurring. A reduction in dosage or withdrawal of the drug The UK CSM15 reported in 2003 that pergo/ide had been 1. Merola B, et al. Allergy to ergot-derived dopamine agonists. Lancet 1992; may be appropriate. Because of the .risk of fibrosis 339: associated with cases of cardiac valvulopathy; since 1989, 620. bromocriptine is contra-indicated in patients with pre valvulopathy had been reported in fewer than 5 in 100 000 existing valve problems. Oedema. Oedema poorly responsive to diuretics has been patients. The CSM also referred to a published case series16 Patients on long-term, high-dose therapy should be reported1 in a patient given bromocriptine as part of treat which reported on 3 patients with severe tricuspid monitored for signs of progressive fibrotic disorders such as ment for prolactinoma. The oedema improved on substitu regurgitation after long-term pergolide treatment. The retroperitoneal fibrosis and bromocriptine withdrawn if tion of pergolide but worsened with higher doses. Oedema authors of this case series and the CSM both considered that, fibrotic changes are diagnosed or suspected. It is resolved when treatment was changed to quinagolide. The based on the available evidence, there was a potential recommended that baseline investigations such as reaction was considered to be idiosyncratic since enquiries association between pergolide and cardiac valvulopathy. erythrocyte sedimentation rate, urea and electrolyte by the author of the report had revealed only one similar Subsequently, the FDN7 stated that, up to the end of 2002, concentrations, and a chest x-ray should be performed case. In a subsequent report2 a patient with Parkinson's it was aware of 15 cases of valvular heart disease with before starting treatment with bromocriptine. Periodic disease who had been receiving bromocriptine for 5 years pergolide treatment; this figure included the 3 cases monitoring of cardiovascular, haematopoietic, hepatic, and developed marked lower leg oedema, and subsequently reported in the above series and 4 cases from the UK. A later renal function is also recommended. Monitoring of visual cough, dyspnoea, and chest pain associated with an exu studyl8 that examined 78 patients taking pergolide for fields is recommended in patients with macroprolactinoma. dative pleural effusion; there was no evidence of fibrosis. Parkinson's disease found evidence of restrictive valvular Both oedema and effusion had largely resolved within 4 heart disease in 15 of 52 (29%) patients taking doses less Breast feeding. The American Academy of Pediatrics1 con weeks of stopping bromocriptine. than 5mg daily and in II of 26 (42%) receiving doses of siders that bromocriptine should be given with caution to 1. Blackard WG. Edema-an infrequently recognized complication of 5 mg or more daily. Pulmonary fibrosis and retroperitoneal breast-feeding mothers, since it suppresses lactation and bromocriptine and other ergot dopaminergic drugs. Am J Med 1993; 94: may be hazardous to the mother. fibrosis have also been associated with pergolide 445. treatment; 19-21 in most cases, symptoms improved when 2. Messiaen T, et al. :Epanchement pleural et importants �rdCmes des 1. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics2001; 108: 776-89. [Retired May the drug was stopped. Duration of exposure to pergolide membres inferieurs induits par la bromocriptine. Rev Med Interne 1996; 17: 680-3. 2010} Correction. ibid.; 1029. Also available at: http:l/aappolicy. ranged from 6 months20 to II years.21 aappublications.org/cgi/ content/full/pediatrics% 3b l 08/3/776 (accessed 16/02/06) In April 2002 the CSM22 calculated crude reporting rates Overdosage. The most striking symptom in two children of fibrotic reactions associated with the ergot derivative aged 2 and 2V2 years who accidentally ingested an esti Porphyria. The Drug Database for Acute Porphyria, com dopamine agonists (bromocriptine, cabergoline, lisuride, mated 25 and 7.5 mg of bromocriptine, respectively, was piled by the Norwegian Porphyria Centre (NAPOS) and and pergolide), based on data submitted to its Yellow Card lethargy with altered mental status 1 The first child vom the Porphyria Centre Sweden, classifies bromocriptine as scheme and estimated drug exposure. Pergolide was found ited and became sleepy. On admission he was markedly probably porphyrinogenic; it should be prescribed only for to be associated with a higher reporting rate of fibrotic lethargic, but combative when disturbed, and also had compelling reasons and precautions should be considered reactions compared with the other ergot derivatives; hypotension, shallow breathing, dilated pupils, and hyper in all patients.I however, this result needed further investigation to see if it reflexic lower extremities. Nasogastric lavage was 1. The Drug Database for Acute Porphyria. Available at: http://www. reflected a true increase in risk or was due to factors such as promptly performed, and activated charcoal and then drugs-porphyria.org (accessed 30/09/ll) reporting biases. There is some evidence that the incidence magnesium citrate given. Blood pressure and ECG were of reactions to pergolide are dose-related; doses are monitored, and glucose and sodium chloride solution Pregnancy. Details of various surveys of the effect of the restricted in many countries (see p. 910.3) and in June 2008 infused. The other child vomited, became lethargic, and use of bromocriptine during pregnancy have been pub the EMEA recommended a maximum dose of 3 mg daily 7 had dilated pupils. Ipecacuanha was given, and activated lished by the manufacturer.1•2 The first survey was based Pergolide was withdrawn from the market in the USA and charcoal followed by magnesium citrate given by nasogas on spontaneous reporting of all pregnancies between 1973 Canada. It is recommended that baseline investigations such tric tube. Both children recovered completely. and 1980 in women who had taken bromocriptine after as erythrocyte sedimentation rate, urea and electrolyte I. Vermund SH, et al. Accidental bromocriptine ingestion in childhood. J conception.1 Information was obtained on 1410 pregnan concentrations, and a chest x-ray should be performed Pediatr 1984; 105: 838--40. cies in 1335 women, the majority of whom had been trea before starting treatment with this class of drugs. ted for hyperprolactinaemic conditions, while in 256 preg et al. Withdrawal syndromes. Transient galactorrhoea and 1. Champagne S, Chronic constrictive pericarditis induced by long nancies pituitary tumours and acromegaly were the term bromocriptine therapy: report of two cases. Ann Pharmacother 1999; hyperprolactinaemia occurred in a young woman after 33: primary diagnosis. Bromocriptine was generally taken at 1050--4. withdrawal of bromocriptine therapy for Parkinson's dis 2. Serratrice J, et al. Fibrotic valvular heart disease subsequent to some time in the first 8 weeks after conception, the mean ease.1 It was suggested the effects were due to a rebound bromocriptine treatment. Cardiol Rev 2002; 10: 334-6. duration of treatment being 21 days. In 4 patients bromo phenomenon. For discussion of a syndrome resembling 3. Vergeret J, et a!. Fibrose pleuro-pulmonaire et bromocriptine. Sem Hop criptine was not prescribed until late in pregnancy and in Paris 1984; 60: 741--4. neuroleptic malignant syndrome that has developed on 9 with acromegaly and pituitary microadenoma it was 4. Kinnunen E, Vi\janen A. Pleuropulmonary involvement during withdrawal of bromocriptine and other antiparkinsonian Chest taken continuously throughout gestation. There were 157 bromocriptine treatment. 1988; 94: 1034-6. drugs, see under Levodopa, p. 906.2. 5. Macak lA, et al. Bromocriptine-induced pulmonary disease. Can J Hosp (II. I%) spontaneous abortions, 12 (0.9%) extrauterine 1. Pentland B, Sawers JSA. Galactorrhoea after withdrawal of bromo Pharm 1991; 44: 37-8, xxiv. pregnancies, 2 patients with 3 hydatidiform moles (0.2%), 6. Debove P, et al. Pleuropneumopathie Ia bromocriptine chez un criptine. BMJ 1980; 281: 716. a and an incidence of twin pregnancies of 1.8%. Major con parkinsonien: revue de Ia litt€rature a propos d'une nouvelle observation. Ann Med Interne(Paris) 1998; 149: 167-71. genital abnormalities were detected in 12 (I%) infants at 7. EMEA. EMEA recommends new warnings and contraindications for Precautions birth and minor abnormalities in 31 (2.5%). A second sur ergot-derived dopamine agonists (issued 26th June, 2008). Available at: Patients with hyperprolactinaemia should be investigated vey, 2 which consisted of formal monitoring of the use of http: //www. emea .europa. eu/pdfs/human/press/pr /32239 5 08en.pdf for the possibility of a pituitary tumour before treatment bromocriptine at 33 clinics between 1979 and 1980, col (accessed 08/08/08) 8. Bhatt MH, et a!. Pleuropulmonary disease associated with dopamine with bromocriptine. Malignancy must be excluded in lected data on a further 7 43 pregnancies in 668 women agonist therapy. Ann Neurol 1991; 30: 613-16. patients with cyclical benign breast disorders such as and had similar findings. The incidence rates reported in 9. Geminiani G, et at. Cabergoline in Parkinson's disease complicated by mastalgia. Annual gynaecological examinations (or every 6 these surveys were comparable with those quoted for nor Mov Disord II: motor fluctuations. 1996; 495-500. months for postmenopausal women) are recommended. mal populations and the data indicate that the use of 10. Ling LH, et al. Constrictive pericarditis and pleuropulmonary disease linked to ergot dopamine agonist therapy (cabergoline) for Parkinson's Treatment of women with hyperprolactinaemic amenor bromocriptine in the treatment of women with infertility disease. Mayo Clin Proc 1999; 74: 371-5. rhoea results in ovulation; patients not wishing to conceive is not associated with an increased risk of abortion, multi II. Townsend M, Maciver DH. Constrictive pericarditis and pleuropulmon should be advised to use contraceptive measures although ple pregnancy, or congenital abnormalities. Furthermore, ary fibrosis secondary to cabergoline treatment for Parkinson's disease. oral contraceptives should be avoided because they may follow-up, for up to 9 years, of 546 children exposed to Heart 2004; 90: e47. 12. Horvath J, et al. Severe multivalvular heart disease: a new complication increase prolactin levels. Acromegalic patients should be bromocriptine in utero found no evidence that bromo of the ergot derivative dopamine agonists. Mov Disord 2004; 19: 656-62. checked for symptoms of peptic ulceration before therapy criptine had any adverse effect on postnatal development -' 13. Pinero A, et al. Cabergoline-related severe restrictive mitral regurgita and should immediately report symptoms of gastrointestinal Nevertheless, since the risk of abortion is not increased by 353: tion. N Eng! J Med 2005; 1976-7. discomfort during therapy. interruption of treatment, licensed product information 14. Australian Adverse Drug Reactions Advisory Committee (ADRAC). In general, bromocriptine should be given with caution Ergot derivatives and fibrotic reactions. Aust Adverse Drug React Bull 2006; recommends that bromocriptine therapy be stopped as 25: 3. Also available at: http:f/www.tga.health.gov.au/adr/aadrb/ to patients with cardiovascular disease, Raynaud's soon as pregnancy is confirmed unless there is a definite aadr0602.pdf (accessed 30/05/08) syndrome, or a history of psychosis. It is contra-indicated indication for its continuation.
All cross-references refer to entries in Volume A 899
See also Pref,'Tlancy, under Hyperprolactinaemia and is biphasic; half-lives of about 4 to 4.5 hours and 15 hours, Prolactinomas, p. 896.2. respectively have been reported for the 2 phases. It is (details are given in Volume B) l. et a!. excreted mainly in faeces via the bile, with small amounts in Proprietary Preparations Turkalj I, Surveillance of bromocriptine in pregnancy. lAMA 1982; 247: l589-9l. urine. Single�ingredient Preparations. Ger.: Parkinsan. 2. Manka C. Bromocriptine in pregnancy: safety aspects. Klin In a study involving 10 patients with Parkinson's disease, 1987; 65: 823-7. single oral doses of bromocriptine 12.5, 25, 50, and lOOmg resulted in very variable peak plasma concentrations Cabergoline (BAN USAN, r/NN) Interactions ranging from 1.3 to 5.3, 1.4 to 3.5, 2.6 to 19.7, and 6.5 to FCE."2 1 336; Kaber' Dopamine antagonists such as the phenothiazines, butyro 24.6 nanograms/mL, respectively, 30 to 210 minutes (mean Cabergoiir:; CabiirgoHna; . Cabergolinl!m;·. phenones, thioxanthenes, and metoclopramide (but see 102 minutes) after dosage.1 After 4 hours plasma gotilni; l<'.aberg{)lin; Ka bergolina; below) might be expected to reduce the prolactin-lowering concentrations were about 75% of the peak values. Clinical 1"[(6:Aiiylergolin-813·yl)carbonyi]-Ka6eprl ··[�,(dronY�Hmethyiam ino)p(O' and the antiparkinsonian effects of bromocriptine and improvement was evident within 30 to 90 minutes of a dose P>:llc3-ethylpreo:. (8Ri'6cA!IyHI/-[3,(cllmethylamioo)propyi]'N domperidone might reduce its prolactin-lowering effect. with peak effect at about 130 minutes and in most patients (ethrlcarb�m0yi)ergpl!f1e,8:-eari;Joxam!Cle', Memantine may enhance the effects of bromocriptine. improvement persisted throughout the 4-hour study period. Stimulants of gastrointestinal motility such as macrolide Peak clinical response, peak fall in blood pressure, and peak C26f:h,iN,Op45CAS '.:.:. <3 1409-90-1.L6 antibacterials or octreotide can increase the bioavailability rise in plasma concentrations of growth hormone occurred of brornocriptine. about 30, 60, and 70 minutes, respectively after peak AT( -,.,..G02CB03; Q0o2C803; .N04BC06. plasma-bromocriptine concentrations but there was no ;\TC Ve t-. - Alcohol. Alcohol intolerance was noted in 5 of 73 patients significant relationship between them. However. there was �: UNII .LL60K9J05 T. receiving bromocriptine 10 to 60mg daily for the treat a significant relationship between plasma concentrations Pharmacopoeias. In Bur. (see p. vii) and US. ment of acromegaly.1 Two patients who had gastrointest and concurrent changes in clinical response compared with Ph. Eur. 8: (Cabergoline). A white or almost white, inal adverse effects while taking low doses of bromo� pretreatment scores. Dyskinesias occurred within 90 to 180 crystalline powder. It exhibits polymorphism. Practically criptine had a marked reduction in their symptoms and minutes of dosage in 5 of 10 patients. insoluble in water; freely soluble in alcohol; very slightly were able to tolerate higher doses when they refrained Bromocriptine is well absorbed from standard oral tablets soluble in n-hexane. It is slightly soluble in O.IM completely from alcohol.' placed in the vagina and plasma concentrations sufficient to hydrochloric acid. Protect from light. et al. lower plasma prolactin concentrations have been achieved 1. Wass JAH, Long-term treatment of acromegaly with bromocriptine. USP 36: ( Cabergoline). A white or almost white, crystalline BMJ 1977; 1: 875�8. using this route.2'3 2. J, Maisey MN. Alcohol increases bromocriptine's side effects. N powder. Practically insoluble in water; freely soluble in I. Price P, et al. Plasma bromocriptine levels, clinical and growth hormone 1980; 302: 806. responses in parkinsonism. Br J Clin Pharmacol 1978; 6: 303-9. alcohol; slightly soluble in O.lM hydrochloric acid; very 2. Vermesh M, et a!. Vaginal bromocriptine: phannacology and effect on slightly soluble in hexane. Store in airtight containers. Antibacterials. Drowsiness, dystonia, choreoathetoid dys serum prolactin in normal women. Obstet Gynecof 1988; 72: 693�8. Protect from light. kinesias, and visual hallucinations occurred when josamy 3. Katz E, et a!. Successful treatment of a prolactin-producing pituitary dn was given to a patient receiving bromocriptine. 1 macroadenoma with intravaginal bromocriptine mesylate: a novel approach to intolerance of oral therapy. Obstet Gynecol l989; 73: 517-20. The systemic bioavailability of a single oral dose of Uses and Administration bromocriptine 5 mg was markedly increased in 5 healthy Cabergoline, an ergot derivative, is a dopamine Dragonist subjects after treatment with erythromycin estolate 250 mg r (]r i with actions and uses similar to those of bromocriptine four times daily for 4 days;2 clearance of bromocriptine was P.. �p <:Ji <:>n.�.. (p. 895.3). It is a potent and long-lasting inhibitor of decreased and peak plasma concentrations of bromocriptine ProprietaryPreparations (details are given in Volume B) prolactin secretion used in the management of disorders were more than 4 times higher than when given alone. associated with hyperprolactinaemia (p. 900. 1). It is also Arg.: Parlodel; Austral. : Bromo 1. Montastruc JL, Rasco] A. Traitement de la maladie de Parkinson par Single-ingredient Preparafions. used to suppress puerperal lactation for medical reasons doses ClevCes de bromocriptine: interaction possible avec la josamycine. hexalt; Kripton; Parlodel; Austria: Parlodel; Umprel; Belg. : (p. 900. 1 ); it is not recommended for the routine Presse Med 1984; 13: 2267-8. Parlode1; Braz.: Bagrent; Parlodel; Chile: Criten; Grifocriptina; suppression of physiological lactation or for the treatment et al. lli�� 2. Nelson MV, Pharrnacokinetic evaluation of erythromycin and Kriptonal; Parlodel; Prigost; China: Baimoting ( )t; of postpartum breast pain and engorgement that may be caffeine administered with bromocriptine. Clin Phannacol Ther 1990; 47: Parlodel; Cz.: Medocriptine; Parlodel; Denm.: Parlodel; Fin.: adequately relieved with simple analgesics and breast 694-7. Parlodel; Fr.: Bromo�Kin; Parlodel; Ger.: kirim gynt; kirim; support. Cabergoline is also used in the management of Pravidel; Gr.: Parlodel; Serocryptin; Hong Kong: Bromergon; Parkinson's disease (p. 900.1) as monotherapy, or as an Antifungols. The response to bromocriptine was blocked Medocriptine; Parlodel; Syntocriptine; India: Briptin; Brom; in a patient who was also receiving griseofulvin.1 Bromogen; Criptal; Encript; Kripti; Ovucript; Sicriptin; Indon.: adjunct to levodopa therapy to reduce 'end-of-dose' or 'on 1. Schwinn G, et al. Metabolic and clinical studies on pntients -with Cripsa; Parlodel; Irl.: Parlodel; Israel: Parilact; Parlodelt; !tal.: off' fluctuations in response; in the UK cabergoline is acromegaly treated with bromocriptine over 22 months. Bur J Clin Invest Parlodel; Jpn: Parlodel; Malaysia: Medocriptine; Parlodel; Mex. : restricted to patients who are intolerant of, or who do not 7: 1977; 101-7. Biodel; Broptin; Crilemt; Cryocriptinat; Kriptisert; Mesiken; respond to, non�ergot drug treatment. Parlodel; Neth.: Parlodel; Norw.: Parlodel; Philipp.: Parlodel; : Cabergoline is given orally and should be taken with Antineoplastics. Tamoxifen may increase the dopaminergic Provasyn; Pol.: Bromergon; Bromocorn; Ergolaktynat; food. effect of bromocriptine; for the effect of bromocriptine on Parlodel; Port. : Parlodel; Rus.: Bromergon (EpOM3proH); Parlodel To inhibit physiological lactation, cabergoline is tamoxifen, see Interactions, under Tamoxifen, p. 863.2. (Ilapno,uen); S.Afr. : Parlodel; Singapore: Brameston; Butint; given as a single 1-mg dose on the first day post partum. For Parlodel; Spain: Parlodel; Swed.: Pravidel; Switz. : Parlodel; suppression of established lactation, the dose is Antipsychotics. Serum concentrations of prolactin rose Thai. : Brocadent; Bromergon; Parlodel; Suplac; Turk.: Galak� 250 micrograms every 12 hours for 2 days. and visual fields deteriorated when thioridazine was given tomin; Gynode1; Parlodel; UAB: Antiprotin; UK: Parlodel; Ukr.: In the treatment of disorders associated with to a 40�year-old man receiving bromocriptine therapy for Parlodel (Ilaprro�e.rr)t; USA: Cycloset; Parlodel; Venez. : Parlodel. hyperprolactinaemia, the initial dose of cabergoline is a large prolactinoma. 1 500 micrograms weekly. The dose is then increased at For a discussion of the effect of bromocriptine on patients Pharmacopoeial Preparafions monthly intervals in increments of 500 micrograms weekly receiving antipsychotics, see Antiparkinsonian Drugs under BP 2014: Bromocriptine Capsules; Bromocriptine Tablets; according to response. The weekly dose may be given on a Chlorpromazine on p. 1052.3. USP 36: Bromocriptine Mesylate Capsules; Bromocriptine single occasion or divided into 2 or more doses on separate Mesylate Tablets. l. Robbins RJ, et a!. Interactions between thioridazine and bromocriptine days according to tolerance; doses over 1 mg should be given in a patient with a prolactin-secreting pituitary adenoma. Am J Med 1984; 76: 921-3. as divided doses although the maximum single daily dose should not exceed 3 mg. The usual dose is I mg weekly but Metoclopromide. As noted in Interactions, above, there up to 4. 5 mg weekly has been used. are theoretical reasons to suppose that dopamine antago In Parkinson's disease, cabergoline should be nists such as metoclopramide might reduce the effects of introduced gradually and during this period the dose of bromocriptine. However. an early study1 in 10 patients levodopa may be reduced gradually until an optimal with Parkinson's disease given single doses of bromo response is achieved. A suggested initial dose of cabergoline criptine 12.5 to IOOmg found that pretreatment with given as a single daily dose is 500 micrograms in metoclopramide 60 mg had no consistent effect upon monotherapy or I mg in adjunctive therapy. The dose plasma concentrations of bromocriptine or growth horm may be increased in increments of 0.5 or 1 mg, at intervals of one and no consistent effect upon clinical response. 7 or 14 days. to 2 to 3 mg daily. The EMEA has clinical and growth hormone recommended a maximum dose of 3 mg daily. responses in parkinsonism. 1978; 6: 303-9. Doses of cabergoline may need to be reduced in patients with severe hepatic impairment (see below). Sympathomimetics. There have been isolated reportsl.2 of severe hypertension, with headache and life-threatening Budipine is a phenylpiperidine derivative used as an adjunct Administration in hepatic impairment. Licensed product complications, in patients taking bromocriptine with iso� in the treatment of parkinsonism (p. 889.1 ). It is given orally information recommends caution in patients with severe metheptene mucate or phenylpropanolamine. as the hydrochloride in daily doses of up to 60 mg. Budipine hepatic impairment (Child-Pugh category C), and doses of l. Kulig K, et a!. Bromocriptine-associated headache: possible life has been reported to prolong the QT interval. cabergoline should be adjusted accordingly. threatening sympathomimetic interaction. Obstet Gyneco! I99l; 78: 941- 3. Acromegaly. Dopaminergics can produce a paradoxical et al. 2. Chan JCN, Postpartum hypertension, bromocriptine and l. Spieker S, et a!. Tremorlytic activity of budipine: a quantitative study 8: reduction in growth hormone secretion and may be used phenylpropanolamine. Drug invest 1994; 254-6. Clin Neuropharmacol 18: with long-term tremor recordings. 1995; 266- in the treatment of acromegaly as adjunctive therapy to 72. 2. Groen H, et a!. A study to investigate the pharmacokinetics and surgery, radiotherapy, or somatostatin analogues to reduce Pharmacokinetics metabolism of budipine after administration of a single oral dose of circulating growth hormone concentrations, although Bromocriptine is rapidly absorbed from the gastrointestinal [14CJ-B757-0l to six healthy volunteers. Br J Clin Pharmacal 1999; 48: they are less effective than somatostatin analogues tract and peak plasma concentrations occur within 1 to 3 77lP-772P. (p. 1921.1). 3. Maisch U, et a!. Monotherapie der Parkinsonschen Erkrankung mit hours after oral doses. However. only about 30% of an oral Budipin: ein randomisierter Doppelblindvergleich mit Amantadin. A smaU study comparing cabergoline with depot dose is absorbed and, owing to extensive first�pass Fortschr Neurol Psychiatr 2001; 69: 86-9. bromocriptine and quinagolide failed to find evidence of metabolism, the bioavailability is only about 6%. It has 4. Przuntek H, et al. Budipine provides additional benefit in patients with its efficacy. 1 However, in a later open study2 there was a been reported to be 90 to 96% bound to serum albumin in Parkinson disease receiving a stable optimum dopaminergic drug good response in about 40 % of patients treated with regimen. Arch Neural 2002; 59: 803-6. vitro. It is metabolised in the liver, mainly by hydrolysis to 5. Reichmann H. Budipine in Parkinson's tremor. J Neural Sci 2006; 248: cabergoline, which is better than the response usually lysergic acid and peptides. The elimination of bromocriptine 53-5. reported for bromocriptine. The addition of cabergoline has
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