Kinetica Drug Interactions

Alcohol: As with other centrally-active medications, patients should be cautioned not to concomitantly take ropinirole with alcohol.
Antihypertensives: There is limited experience with ropinirole in patients treated with antihypertensive and antiarrhythmic agents. Consequently, in such patients, the dose of ropinirole should be titrated with caution.
Central nervous system (CNS) depressants: Because of the possible additive sedative effects, caution should be observed when coadministering ropinirole with CNS depressants (e.g., benzodiazepines, antipsychotics, antidepressants).
CYP1A2 inhibitors or inducers: In vitro studies demonstrated that CYP1A2 was the major enzyme responsible for the metabolism of ropinirole. Thus, coadministration of the inhibitors or inducers of this enzyme may alter the clearance of ropinirole. Dose adjustments may be necessary if a potent inhibitor of CYP1A2 is discontinued or initiated during treatment with ropinirole.
The extent of systemic availability and peak plasma concentration of ropinirole 2 mg immediate-release tablet given three times a day was increased by 60% and 84%, respectively, with the coadministration of ciprofloxacin. Cigarette smoking is expected to increase the clearance of ropinirole since it is known that smoking induces CYP1A2 activity. Adjustments in ropinirole doses may be required in patients who are smoking or in those planning to stop smoking.
In patients already administered with CYP1A2 inhibitor (e.g., ciprofloxacin, enoxacin, cimetidine, fluvoxamine), ropinirole may be started in the recommended manner and the dose be titrated according to clinical response. However, ropinirole dosage adjustments will be required if therapy with a CYP1A2 is discontinued or introduced during ropinirole treatment.
CYP1A2 substrates: A pharmacokinetic study revealed that there is no change in the pharmacokinetics of both ropinirole and theophylline, a representative of substrates of CYP1A2. Therefore, there are no expected changes in the pharmacokinetics of ropinirole coadministered with other CYP1A2 substrates.
Digoxin: At steady state, coadministration of ropinirole 2 mg given three times daily resulted in a 10% decrease in digoxin AUC, while mean trough digoxin plasma concentrations were not altered. The effect of higher recommended ropinirole doses on the pharmacokinetics of digoxin is not yet known.
Domperidone: No dose adjustment is needed during the coadministration of ropinirole with domperidone, a peripherally-active dopamine agonist.
Drugs used to treat Parkinson's disease: No interaction was observed between ropinirole and other drugs commonly used to manage Parkinson's disease.
Hormone Replacement Therapy (HRT): Higher doses of estrogens (0.6 to 3 mg), predominantly conjugated estrogens, decreased the clearance of ropinirole by 33% in postmenopausal women receiving HRT. Ropinirole treatment may be started in the normal manner. However, adjustments of ropinirole dosage may be required when concomitant HRT is initiated or discontinued.
Levodopa: In levodopa-naive patients, the rate and extent of availability of ropinirole 2 mg administered three times a day at steady state were the same with or without levodopa. The rate and extent of availability, as well as the elimination half-life of levodopa, were unchanged in the presence and absence of ropinirole. There is no pharmacokinetic interaction between ropinirole and levodopa that would require dosage adjustments of either drugs.
Psychotropic Drugs: The concomitant use of ropinirole with neuroleptics (e.g., phenothiazines, butyrophenones, thioxanthenes) or other centrally-active dopamine antagonists (e.g., metoclopramide, sulpiride) is not recommended because these drugs may diminish the effect of ropinirole.
Vitamin K antagonists: Cases of unbalanced international normalized ratio (INR) have been reported in patients receiving ropinirole with vitamin K. Increased clinical and biological surveillance of INR is recommended.