Ropinirole dosing

CH returns to the clinic 3 months later. The physician previously diagnosed him with obstructive sleep apnea and RLS. He received a prescription for CPAP, for OSA and ropinirole 0.5 mg at bedtime for RLS at his last visit. Via phone calls, his ropinirole dose has been increased to 3 mg at bedtime. He has received moderate relief of his RLS symptoms, but on occasion, he still awakens and cannot fall back asleep. His sleepiness and RLS symptoms are improved ESS 13/24. 

Ciprofloxacin increased the AUC of ropinirole by 84%, and other CYP1A2 inhibitors are predicted to interact similarly. Ropinirole dose adjustment may be required if potent CYP1A2 inhibitors are started or stopped. 

Although the clinical relevance of this pharmacokinetic interaction has not been assessed, it would seem possible that the effects of ropinirole may be increased. The manufacturers suggest that if therapy with a known potent inhibitor of CYP1A2 is stopped or started during therapy with ropinirole, adjustment ofthe ropinirole dose may be required. The UK manufacturer specifically mentions cimetidine and fluvoxamine in addition to ciprofloxacin. For a full list of CYP1A2 inhibitors, see Table 1.2 , (p.4). 

Ropinirole (Requip ) Activate postsynaptic D2 DA receptors Start with 0.25 mg three times daily increase about weekly by 0.75-1.5 mg daily to a MD dose of 3-8 mg three times daily... 

L-DOPA can be initiated at 50 mg taken at bedtime and increased stepwise over a few weeks until the symptoms are relieved. Bromocriptine can be initiated at 7.5 mg at bedtime, pramipexole is often dosed at 0.125-0.375 mg at night, and ropinirole, which has an indication for RLS, is typically administered at 0.25-3 mg at bedtime. These medications are not without side effects. They may cause nausea and, over time, insomnia. Less commonly, these medications can cause hallucinations or involuntary movements called dyskinesias. These side effects usually resolve rapidly upon discontinuing the medication. 

When ropinirole is administered as adjunct therapy to levodopa, the concurrent dose of levodopa may be decreased gradually as tolerated. Discontinue ropinirole gradually over a 7-day period. Decrease the frequency of administration from 3 times/day to twice/day for 4 days. For the remaining 3 days, decrease the frequency to once/day prior to complete withdrawal of ropinirole. 

In clinical trials of patients being treated for RLS with doses up to 4 mg once daily, ropinirole was discontinued without a taper. 

Because of these adverse effects, the drugs are generally first administered at low doses and then the dose is gradually increased over weeks or months as tolerance to the adverse effects develops. These symptoms are generally less frequent and less severe with pramipexole and ropinirole, which allows for a more rapid achievement of therapeutic response. Also, because pramipexole and ropinirole are better tolerated, they are increasingly used as monotherapy. 

Ropinirole, another nonergoline derivative, is a relatively pure D2 receptor agonist that is effective as monotherapy in patients with mild disease and as a means of smoothing the response to levodopa in patients with more advanced disease and response fluctuations. It is introduced in a dose of 0.25 mg three times daily, and the total daily dose is then increased by 0.75 mg at weekly intervals until the fourth week and by 1.5 mg thereafter. In most instances, a dose of between 2 and 8 mg three times daily is necessary. Ropinirole is metabolized by CYP1A2 drugs metabolized by the liver may significantly reduce its clearance. 

PRAMIPEXOLE, ROPINIROLE H2-RECEPTOR BLOCKER-CIMETIDINE T efficacy and adverse effects of pramipexole 1 renal excretion of pramipexole by inhibition of cation transport system. Inhibition of CYP1A2-mediated metabolism of ropinirole Monitor closely i dose of pramipexole may be required. Adjust dose of ropinirole as necessaiy or use alternative acid suppression, e.g. H2 antagonist proton pump inhibitor (not omeprazole or lansoprazole)... 

Supraventricular extra beats have rarely been reported after low doses of ropinirole and have also been reported after pergolide and levodopa (1). Symptomatic postural hypotension has occurred after even low oral doses of ropinirole (2-5), related to peripheral dopaminergic activity. Hypotensive effects occur within 3 minutes of standing, usually between 2 and 4 hours after an oral dose, associated with nonspecific malaise (2). Dizziness occurred in up to 40% of patients in clinical trials. Related symptoms include faintness, malaise, and yawning (2). Bradycardia has occasionally accompanied postural hypotension (4). Syncope has been reported. 

Nausea, usually mild and not associated with vomiting, has been reported after oral doses of ropinirole, in both supine and standing positions (1-5). Nausea is related to peripheral dopaminergic activity and has been controlled by pretreatment with domperidone (20 mg) (2,3). In one study in healthy subjects, nausea was not reported in the supine position after oral ropinirole however, nausea with malaise was common on standing (orthostatic symptoms) (2). 

A 49-year-old man with Parkinson s disease was treated with ropinirole, and the dosage eventually reaching 3 mg tds. He had penile erections 20-30 minutes after each dose, lasting for 10-15 minutes. They were not associated with arousal and were very uncomfortable he had no history of sexual dysfunction. Their frequency diminished with a reduction in drug dosage, but they stopped completely only on drug withdrawal. 

Fine J, Lang AE. Dose-induced penile erections in response to ropinirole therapy for Parkinson s disease. Mov Disord 1999 14(4) 701-2. 

Pramipexole is initiated at a dose of 0.125 mg three times a day and increased every 5 to 7 days as tolerated. In a fixed-dose study, daily doses of 3, 4.5, and 6 mg were not more effective than 1.5 mg/day, and the higher doses were associated with a higher frequency of adverse effects. When switching from bromocriptine or pergolide to pramipexole, a 10 1 and 1 1 dosage substitution is recommended, respectively. Ropinirole is initiated at 0.25 mg three times a day and increased by 0.25 mg three times a day on a weekly basis to a maximum of 24 mg/day. The dose of dopaminergic agonists is best determined by slow titration to enhance tolerance and to find the least dose that provides optimal benefit. 

A man stabilised on warfarin had an increase in INR necessitating a 25% decrease in his warfarin dose while taking ropinirole. 

In patients on a stable dose of levodopa with a dopa-decarboxylase inhibitor, ropinirole had no effect on the pharmacokinetics of levodopa, except for a small clinically irrelevant 16% increase in maximum level. Similarly, levodopa had no effect on the pharmacokinetics of ropinirole in another group of patients. As the dose of ropinirole is increased, the dose of levodopa may be reduced gradually, by around 20% in total. ... 

Population pharmacokinetic analysis of clinical study data showed that estrogens (mainly ethinylestradiol ) used in HRT reduced ropinirole clearance by one-third.In another analysis it was found that women taking HRT received a slightly lower daily dose of ropinirole than those not on HRT, with no difference in adverse effects. Therefore, in women already receiving HRT, ropinirole treatment may be started using the usual dose titration.However, it is suggested that a reduction in the ropinirole dosage may be needed if HRT is started, and an increase if it is withdrawn. 

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