Ropinirole
- Article Author:
- Ayesan Rewane
- Article Editor:
- Shivaraj Nagalli
- Updated:
- 7/6/2020 4:38:07 PM
- For CME on this topic:
- Ropinirole CME
- PubMed Link:
- Ropinirole
Indications
Dopamine agonists (DA) are drugs used in the treatment of a variety of central nervous system disorders. The ergoline (e.g., bromocriptine) and non-ergoline dopamine agonist (ropinirole) are very useful in the treatment of Parkinson's disease. Ropinirole is one of the US Food and Drug Administration approved medications indicated for the treatment of restless legs syndrome (RLS) and Parkinson's disease. Pharmacologically, it acts by selectively binding to the D2 receptors. It is effective in the treatment of both early and advanced-stage Parkinson's disease and can improve the "on" time and minimize the "off" time of the disease. It is also helpful in the management of sleep disturbances and nocturnal psychosis associated with Parkinson's disease.[1][2][3]
Parkinson Disease (PD)
Parkinson's disease is a condition characterized by the loss of dopamine receptors in the substantia nigra pars compacta leading to both cognitive and motor decline. The slow movement, stiff joints, and tremors are characteristic features of this disease.[4] There are times when these patients demonstrate good motor function, referred to as 'On', and periods of severe motor decline referred to as 'Off.' Ropinirole is equally effective in the treatment of PD when as monotherapy or in combination with other medications like L-dopa.[5]
Restless Leg Syndrome (RLS)
RLS is also known as Willis-Ekbom disease. It is the uncontrollable urge to move the legs following a sensation commonly described as burning, painful or tingling.[6] Ropinirole also has a role in the treatment of moderate to severe RLS; the relief can occur within two days of commencement of treatment.[7]
Mechanism of Action
Ropinirole has a high affinity for and stimulates the post-synaptic dopamine receptors D2 in the central and peripheral nervous systems. The dopamine receptors (D2) are g-protein-coupled inhibitory neurons predominantly in the striatonigral, mesolimbic, and tuberoinfundibular systems. They inhibit adenylyl cyclase and calcium (Ca2+) channels and activate potassium channels leading to its physiological functions.[8][9]
Administration
Orally; Two oral formulations are available, the immediate release and prolonged/extended-release form. Administration of the immediate-release form is three times daily, while the extended-release is once daily.[1] A high-fat diet may delay the absorption, and it is better absorbed in a fasting state. The metabolism of ropinirole occurs in the liver, and only about 10% is excreted in the urine. The primary liver enzyme involved in metabolizing this drug is the cytochrome P450 (CYP1A2). Ciprofloxacin, an enzyme inhibitor, can increase the plasma level of this drug, and similarly metabolized by the same isoenzyme CYP1A2. Despite this fact, other inducers have not demonstrated an effect on ropinirole's metabolism.[2][10]
On the other hand, the therapeutic level for this drug is between 0.4 and 6 ng/mL; its use requires caution in older patients (greater than 65 years) and women on hormonal replacement therapy (HRT) because of slower clearance of the medication in these groups.[2][11]
In the treatment of PD, a dose within 6 to 24 mg of prolonged-release formulation is usually well-tolerated, but care is necessary to titrate the dose to the symptoms of the disease, and the clinician can individualize this from patient to patient.[12]
For RLS, it is best to take ropinirole about two hours before the onset of symptoms before the symptom starts. A dose of 2 mg or less would suffice, and it is a good practice to start on a low dose. Ropinirole, in patients with RLS, is usually started at a dose of 0.25 mg per day, with an increment of 0.25 mg every two to three days until the reduction of symptoms.[13]
Adverse Effects
As with most dopamine agonists, the most frequently reported adverse effects of ropinirole are nausea, vomiting, abdominal pain, hallucinations, somnolence, dizziness, and orthostatic hypotension.[9][14][15]
Peripheral Edema
Reports exist of peripheral edema in patients on the extended-release form recorded in up to one-third of the patient on the extended-release form.[16]
Anterocollis
The definition of this condition is the head positioned in flexion, resembling a "drooping head," a very rare side effect reported in a patient taking ropinirole. Discontinuation of the medication progressively reversed the symptoms over about four months.[17]
Pisa Syndrome
Cases of ropinirole-induced Pisa syndrome, also referred to as "pleurothotonus," have appeared in the literature. It is characterized by an abnormal lateral flexion of the trunk to the right or left. This condition occurred after about a year on the medication among the cases described. The posture disappeared about there months after discontinuing the medication. However, Pisa syndrome is reportedly irreversible despite discontinuing this medication.[18][19]
Reversible Dyskinesias
Another movement disorder observed with ropinirole is severe reversible dyskinesias, very rare. This dose-dependent choreoform dyskinesia occurred in ropinirole monotherapy up to a dose of 15 mg daily but was also observed at a dose of 6 mg daily.[20]
Dermal Eruptions
Similar to many D2 agonists, ropinirole in rare cases caused fixed dermal eruptions thought to be due to the inactivation of T cells.[21]
Contraindications
Clinicians should avoid using ropinirole in persons who misuse alcohol and patients with liver failure.
Toxicity
Ropinirole can cause death when taken with alcohol, and by persons with excessive alcohol intake should not use the drug. A lethal level up to six times the therapeutic dose has correlations with death.[11] Patients with liver insufficiency require close monitoring; a report of a case of liver toxicity exists. The medication is metabolized majorly in the liver, and the toxicity may be due to an immune reaction or a possible toxic metabolite of the drug.[1]
Enhancing Healthcare Team Outcomes
Patients and caregivers should receive education about the medication, its use, side effects, signs of toxicity, and compliance. Compliance with medication can be very challenging, especially in PD, and once-daily prolonged release ropinirole greatly improves medication compliance. Additionally, the severity of the motor symptoms such as tremor and rigidity may also be an important factor to consider to improve compliance and management of these patients.[1][9][22] This is where an interprofessional team approach is most beneficial.
RLS, in its chronic state, can be very challenging because of the disruption of sleep for both the patients and family members. Ropinirole has demonstrated an improvement in the quality of sleep, quality of life, and mood of patients with RLS.[13] However, clinicians should try other forms of treatment before the use of dopamine agonists like ropinirole, and once they decide to try ropinirole, it should start at a very low dose. This dosing approach is because chronic use of dopamine agonists causes ‘augmentation,” which is the worsening of symptoms and is often very difficult to treat.[23]
When prescribing ropinirole, the clinician should consider consulting with a pharmacist regarding the appropriateness of therapy, the optimal starting dose, and have the pharmacist check for potential drug-drug interactions. Nursing staff can monitor patient progress with the patient or caregivers, as well as assess compliance, answer questions, and monitor for adverse events, reporting anything of concern to the clinician. These interprofessional team activities can optimize ropinirole therapy and drive better patient outcomes. [Level 5]