Cigarette smoking is expected to increase the clearance of ropinirole since
CYP1A2 is known to be induced by smoking. In one study in patients with Restless
Legs Syndrome, cigarette smokers had an approximate 30% lower Cmax and a 38% lower AUC than did nonsmokers, when those
parameters were normalized for dose.
There is no evidence of interaction between ropinirole and other CYP1A2
substrates (e.g., theophylline).
Ropinirole and its circulating metabolites do not inhibit or induce P450
enzymes therefore ropinirole is unlikely to affect the pharmacokinetics of other
drugs by a P450 mechanism [see Clinical Pharmacology].
[see Clinical Pharmacology ].
Population pharmacokinetic analysis revealed that higher doses of
estrogens (usually associated with hormone replacement therapy [HRT]) reduced
the oral clearance of ropinirole by approximately 35%. Dosage adjustment is not
needed for initiating REQUIP XL in patients on estrogen therapy because patients
are individually titrated with REQUIP XL to tolerance or adequate effect. If
estrogen therapy is stopped or started during treatment with REQUIP XL, then
adjustment of the dose of REQUIP XL may be required.
7.4 Dopamine Antagonists
Since ropinirole is a dopamine agonist, it is possible that
dopamine antagonists such as neuroleptics (e.g., phenothiazines, butyrophenones,
thioxanthenes) or metoclopramide may diminish the effectiveness of REQUIP XL.
Patients with a history or presence of major psychotic disorders should be
treated with dopamine agonists only if the potential benefits outweigh the
10.1 Human Overdose Experience
In the Parkinson's disease program, there have been patients who
accidentally or intentionally took more than their prescribed dose of
ropinirole. The largest overdose reported with immediate-release ropinirole in
clinical trials was 435 mg taken over a 7-day period (62.1 mg/day). Of patients
who received a dose greater than 24 mg/day, reported symptoms included adverse
events commonly reported during dopaminergic therapy (nausea, dizziness), as
well as visual hallucination, hyperhidrosis, claustrophobia, chorea,
palpitations, asthenia, and nightmares. Additional symptoms reported for doses
of 24 mg or less or for overdoses of unknown amount included vomiting, increased
coughing, fatigue, syncope, vasovagal syncope, dyskinesia, agitation, chest
pain, orthostatic hypotension, somnolence, and confusional state.
10.2 Overdose Management
The symptoms of overdose with ropinirole are generally related to
its dopaminergic activity; these symptoms may be alleviated by appropriate
treatment with dopamine antagonists such as neuroleptics or metoclopramide.
General supportive measures are recommended. Vital signs should be maintained,
if necessary. Removal of any unabsorbed material (e.g., by gastric lavage) may