Ropinirole Other names: Ropinotergotirole

A study into the use of ropinirole in patients with end stage renal disease (patients on haemodialysis) has shown that a dose adjustment in these patients is required as follows: the recommended initial dose of ropinirole prolonged-release tablets is 2 mg once daily. Further dose escalations should be based on tolerability and efficacy. The recommended maximum dose of ropinirole prolonged-release tablets is 18 mg/day in patients receiving regular haemodialysis. Supplemental doses after haemodialysis are not required.

In patients receiving the combination of vitamin K antagonists and ropinirole, cases of unbalanced INR have been reported. Increased clinical and biological surveillance (INR) is warranted.

Increased plasma concentrations of ropinirole have been observed in patients treated with high doses of oestrogens. In patients already receiving hormone replacement therapy (HRT), ropinirole treatment may be initiated in the normal manner. However, it may be necessary to adjust the ropinirole dose, in accordance with clinical response, if HRT is stopped or introduced during treatment with ropinirole.

Ropinirole is principally metabolised by the cytochrome P450 isoenzyme CYP1A2. A pharmacokinetic study (with a ropinirole film-coated (immediate-release) tablet dose of 2 mg, three times a day) in Parkinson’s disease patients, revealed that ciprofloxacin increased the C_max and AUC of ropinirole by 60% and 84% respectively, with a potential risk of adverse events. Hence, in patients already receiving ropinirole, the dose of ropinirole may need to be adjusted when medicinal products known to inhibit CYP1A2, e.g. ciprofloxacin, enoxacin or fluvoxamine, are introduced or withdrawn.

Neuroleptics and other centrally active dopamine antagonists, such as sulpiride or metoclopramide, may diminish the effectiveness of ropinirole and therefore, concomitant use of these medicinal products should be avoided.

Due to the risk of hypotension, blood pressure monitoring is recommended, particularly at the start of treatment, in patients with severe cardiovascular disease (in particular coronary insufficiency).

Patients with major psychiatric or psychotic disorders, or a history of these disorders, should not be treated with dopamine agonists unless the potential benefits outweigh the risks.

Smoking is known to induce CYP1A2 metabolism, therefore if patients stop or start smoking during treatment with ropinirole, dose adjustment may be required.

There are no adequate data from the use of ropinirole in pregnant women. Ropinirole concentrations may gradually increase during pregnancy.

Studies in animals have shown reproductive toxicity. As the potential risk for humans is unknown, it is recommended that ropinirole is not used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the foetus.

Ropinirole-related material was shown to transfer into the milk of lactating rats. It is unknown whether ropinirole and its metabolites are excreted in human milk. A risk to the suckling child cannot be excluded. Ropinirole should not be used in nursing mothers as it may inhibit lactation.

Fertility

There are no data on the effects of ropinirole on human fertility. In female fertility studies in rats, effects were seen on implantation but no effects were seen on male fertility.

Patients being treated with ropinirole and presenting with hallucinations, somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until such recurrent episodes and somnolence have resolved.

Undesirable effects reported are listed below by system organ class and frequency. It is noted if these undesirable effects were reported in clinical trials as monotherapy or adjunct therapy to levodopa.

Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

The following adverse drug reactions have been reported in either Parkinson’s disease clinical trials with ropinirole prolonged-release tablets or Ropinirole film-coated (immediate-release) tablets at doses up to 24 mg/day, or from post-marketing reports:

^* Aggression has been associated with psychotic reactions as well as compulsive symptoms.
^** Somnolence has been reported very commonly in the adjunct therapy immediate- release clinical trials, and commonly in the adjunct therapy prolonged-release clinical trials.
^*** In patients with advanced Parkinson’s disease, dyskinesias can occur during the initial titration of ropinirole. In clinical trials it was shown that a reduction of the levodopa dose may ameliorate dyskinesia.
^**** Nausea has been reported very commonly in the adjunct therapy immediate- release clinical trials, and commonly in the adjunct therapy prolonged-release clinical trials.
^***** Non-motor adverse effects may occur when tapering or discontinuing dopamine agonists including ropinirole.