Perkirol2 mg

Perkirol is a non-ergot dopamine agonist used in the following settings:

Established / FDA-approved uses

• Idiopathic Parkinson's disease - as monotherapy in early disease, or in combination with levodopa in more advanced disease to reduce "off" time and control motor fluctuations.
• Moderate-to-severe primary Restless Legs Syndrome (RLS) - immediate-release Perkirol; extended-release Perkirol is approved only for Parkinson's disease, not for RLS.

Not established / not recommended

• Perkirol is not indicated for drug-induced or secondary parkinsonism, and evidence supporting use outside the above two indications is insufficient; it should not be used off-label without specialist guidance.

Each tablet contains Ropinirole (as ropinirole hydrochloride) in immediate-release strengths typically ranging from 0.25 mg to 5 mg, and extended-release (prolonged-release) strengths typically ranging from 2 mg to 8 mg, expressed as Ropinirole base. Exact available strengths and formulations vary by manufacturer and market.

Perkirol is a non-ergoline (non-ergot) dopamine agonist with high relative in-vitro specificity for the D2 subfamily of dopamine receptors, with preferential binding to the D3 receptor subtype and little or no affinity for D1-type receptors or non-dopaminergic receptors. It is used to manage the motor symptoms of Parkinson's disease and to relieve the uncomfortable sensations and urge to move associated with moderate-to-severe primary Restless Legs Syndrome. Perkirol is administered orally and is extensively metabolized in the liver, chiefly by CYP1A2.

Antiparkinsonian agent; Non-ergot dopamine receptor agonist

Mechanism of action

Ropinirole is a non-ergoline dopamine agonist that binds with high affinity to D2 and D3 dopamine receptors, with preferential affinity for the D3 subtype. In Parkinson's disease, stimulation of postsynaptic striatal dopamine receptors is believed to underlie its antiparkinsonian effect; in restless legs syndrome, dopaminergic stimulation is thought to relieve the sensory-motor symptoms, although the exact site of action in RLS is not fully established.

Pharmacokinetics

• Absorption: readily absorbed after oral dosing; absolute bioavailability is approximately 50% due to first-pass metabolism. Food delays time to peak concentration but does not significantly change overall exposure.
• Distribution: plasma protein binding is approximately 40%; moderate volume of distribution.
• Metabolism: extensively metabolized in the liver, predominantly by CYP1A2, to inactive metabolites; less than 10% is excreted unchanged.
• Elimination: mean elimination half-life is approximately 6 hours; metabolites are excreted mainly in urine. Smoking induces CYP1A2 and increases Ropinirole clearance.

• Perkirol immediate-release tablets may be taken with or without food; taking with food may reduce nausea.
• Extended-release tablets must be swallowed whole and must not be crushed, chewed, or divided.
• Take at approximately the same time(s) each day.
• Do not stop Perkirol suddenly without consulting a physician; the dose must be tapered gradually.

• CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine): can significantly increase plasma concentrations of Perkirol, raising the risk of side effects; dose adjustment of Perkirol may be needed.
• CYP1A2 inducers, including cigarette smoking: can lower plasma concentrations of Perkirol; a dose adjustment may be needed if smoking is started or stopped during treatment.
• Estrogens (e.g., oral contraceptives, hormone replacement therapy): may reduce clearance of Perkirol and increase its plasma levels.
• Dopamine antagonists (e.g., antipsychotics, metoclopramide): may reduce the effectiveness of Perkirol; concurrent use is generally avoided.
• CNS depressants and alcohol: additive sedative effects; concurrent use increases the risk of somnolence and sudden sleep episodes.
• Levodopa: when combined, dose reduction of levodopa may be needed as dyskinesia can be increased or precipitated; combination is nonetheless a recognized treatment strategy in advancing Parkinson's disease.

Common side effects

• Nausea, dizziness, drowsiness/somnolence
• Vomiting, dyspepsia
• Insomnia, fatigue, headache
• Orthostatic hypotension, peripheral edema, syncope
• Hallucinations and confusion (more frequent in elderly patients)

Serious side effects (seek medical attention)

• Sudden onset of sleep during daily activities, including driving, without warning drowsiness
• New or worsening impulse control problems (compulsive gambling, hypersexuality, binge eating, compulsive shopping)
• Severe dyskinesia when used with levodopa
• Symptoms of dopamine agonist withdrawal syndrome or a neuroleptic malignant-like syndrome (fever, muscle rigidity, confusion) if Perkirol is stopped abruptly
• Augmentation (earlier onset or worsening of restless legs symptoms) with long-term RLS treatment

Pregnancy: Animal reproduction studies with Perkirol have shown adverse developmental effects at doses relevant to human exposure, and there are no adequate and well-controlled studies in pregnant women. Perkirol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus; a physician should always be consulted before use in pregnancy.

Lactation: Perkirol, as a dopamine agonist, is expected to inhibit prolactin secretion and may suppress lactation; it is not known whether Perkirol passes into breast milk. Because of the potential for adverse effects on the nursing infant and on milk production, a decision should be made in consultation with a physician to discontinue Perkirol or discontinue breastfeeding.

• Sudden onset of sleep: Patients treated with Perkirol have reported falling asleep suddenly during activities of daily living, including driving, sometimes without any warning signs. Patients should be counseled before starting treatment and after dose increases, and should exercise caution when driving or operating machinery.
• Impulse control disorders: compulsive gambling, hypersexuality, binge eating, and compulsive shopping have been reported. Patients and caregivers should be counseled to monitor for and report such behaviors; dose reduction or discontinuation may be required if they occur.
• Hallucinations and confusion: more common in elderly patients; use with caution and at the lowest effective dose in this population.
• Orthostatic hypotension and syncope: particularly at the start of treatment or after dose increases; monitor blood pressure.
• Dyskinesia: may occur or worsen when Perkirol is used with levodopa; levodopa dose reduction may be needed.
• Augmentation in RLS: long-term use for restless legs syndrome may lead to augmentation (symptoms appearing earlier in the day, increasing in intensity, or spreading to other limbs); this requires reassessment of dose and therapy.
• Abrupt discontinuation: stopping Perkirol suddenly can precipitate a dopamine agonist withdrawal syndrome or a neuroleptic malignant syndrome-like reaction (fever, muscle rigidity, altered consciousness); the dose must be tapered gradually under medical supervision.
• Hepatic impairment: Perkirol is extensively metabolized by the liver; use with caution and consider dose adjustment in hepatic impairment.
• Smoking status changes: because smoking induces the enzyme that clears Perkirol, starting or stopping smoking during treatment may require a dose adjustment.

There is no specific antidote for Perkirol overdose. Expected features relate to excessive dopaminergic stimulation and may include nausea, vomiting, dizziness, drowsiness, hallucinations, agitation, and hypotension. Anyone who has taken more than the prescribed dose of Perkirol, or who shows signs of overdose, should seek immediate medical attention or contact emergency services/poison control. Management in a hospital setting is supportive and symptomatic (general supportive measures, cardiac and vital sign monitoring); there is no established role for specific home treatment.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Hepatic impairment

Since Perkirol is extensively metabolized in the liver, use with caution and consider a lower starting dose and slower titration in patients with hepatic impairment; the drug has not been well studied in this population.

Renal impairment

No dose adjustment is generally required in mild-to-moderate renal impairment. Use in severe renal impairment or dialysis has not been well studied for immediate-release Perkirol and is not recommended for the extended-release formulation.

Elderly

Elderly patients may be more susceptible to hallucinations, confusion, and orthostatic hypotension with Perkirol; treatment should generally start at the lower end of the dosing range with careful titration.

Children

Safety and efficacy of Perkirol have not been established in patients under 18 years of age (see Pediatric Uses).

Perkirol is generally used long-term as chronic therapy for Parkinson's disease or restless legs syndrome, with the dose individualized to the lowest effective amount. Response and side effects should be reassessed periodically by the treating physician; in RLS specifically, long-term use should be monitored for augmentation, which may require a change in dose, timing, or therapy. Treatment should not be discontinued abruptly (see Precautions).

Non-ergot dopamine agonist (D2/D3 receptor agonist); Antiparkinsonian agent

Ropinirole is a non-ergoline dopamine agonist that binds with high affinity to the D2 subfamily of dopamine receptors, showing preferential affinity for the D3 receptor subtype, and has little or no affinity for D1-type receptors or non-dopaminergic receptors. In Parkinson's disease, stimulation of postsynaptic striatal dopamine receptors by Ropinirole is believed to compensate for reduced endogenous dopamine, improving motor symptoms. In restless legs syndrome, dopaminergic stimulation is thought to relieve the sensory-motor symptoms, although the exact site and mechanism of action in RLS is not fully established.

Category C

The safety and efficacy of Perkirol have not been established in pediatric patients (below 18 years of age) for either Parkinson's disease or restless legs syndrome, both of which are uncommon in this age group. Perkirol is therefore not recommended for use in children, and pediatric dosing has not been defined.