P 450 Interaction: In vitro metabolism studies showed that CYP1A2 was
the major enzyme responsible for the metabolism of ropinirole. There is thus the potential for substrates or
inhibitors of this enzyme when coadministered with ropinirole to alter its clearance. Therefore, if therapy with a
drug known to be a potent inhibitor of CYP1A2 is stopped or started during treatment with Requip , adjustment
of the Requip dose may be required.
L-dopa: Co-administration of carbidopa + L-dopa (Sinemet® 10/100 mg b.i.d.) with
ropinirole (2.0 mg t.i.d.) had no effect on the steady-state pharmacokinetics of ropinirole (n=28 patients). Oral
administration of Requip 2.0 mg t.i.d. increased mean steady state C max of L-dopa by 20% but its
AUC was unaffected (n=23 patients).
Digoxin: Co-administration of Requip (2.0 mg t.i.d.) with digoxin (0.125-0.25 mg
q.d.) did not alter the steady-state pharmacokinetics of digoxin in 10 patients.
Theophylline: Administration of theophylline (300 mg b.i.d., a substrate of CYP1A2) did
not alter the steady-state pharmacokinetics of ropinirole (2 mg t.i.d.) in 12 patients with Parkinsons disease.
Requip (2 mg t.i.d.) did not alter the pharmacokinetics of theophylline (5 mg/kg i.v.) in 12 patients with
Ciprofloxacin: Co-administration of ciprofloxacin (500 mg b.i.d.), an inhibitor of
CYP1A2, with ropinirole (2 mg t.i.d.) increased ropinirole AUC by 84% on average, and C max by 60% (n=12
Estrogens: Population pharmacokinetic analysis revealed that estrogens (mainly
ethinylestradiol: intake 0.6-3 mg over 4-month to 23-year period) reduced the oral clearance of ropinirole by 36% in
16 patients. Dosage adjustment may not be needed for Requip in patients on estrogen therapy because patients
must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped
or started during treatment with Requip , then adjustment of the Requip (ropinirole hydrochloride) dose may be
Dopamine Antagonists: Since ropinirole is a dopamine agonist, it is possible that
dopamine antagonists, such as neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may
diminish the effectiveness of Requip . Patients with major psychotic disorders, treated with neuroleptics,
should only be treated with dopamine agonists if the potential benefits outweigh the risks.
Population analysis showed that commonly administered drugs, e.g., selegiline, amantadine, tricyclic
antidepressants, benzodiazepines, ibuprofen, thiazides, antihistamines, and anticholinergics did not affect the oral
clearance of ropinirole.