Istradefylline, known by its brand name Nourianz, is a medication approved for use in adults. Its specific purpose is to manage “off” episodes experienced by individuals living with Parkinson’s disease. This medication functions as an add-on therapy alongside existing treatments. It aims to reduce periods when Parkinson’s symptoms return or worsen despite ongoing medication.
How Istradefylline Works in the Brain
Istradefylline operates by targeting adenosine A2A receptors located in the brain, particularly within the basal ganglia. This brain region plays a significant role in controlling movement. In Parkinson’s disease, a deficiency of dopamine leads to an imbalance in brain pathways that affect motor control.
Adenosine A2A receptors are abundant in areas that interact with dopamine pathways. Under typical conditions, adenosine can act as an inhibitory signal, counteracting dopamine’s effects. By blocking these A2A receptors, istradefylline indirectly enhances the activity of dopaminergic pathways, which helps improve motor function. This mechanism is distinct from traditional Parkinson’s medications that directly replace or mimic dopamine. It is thought to reduce an overactive “no-go” pathway that hinders movement, effectively “releasing a brake” on motor control.
Use in Parkinson’s Treatment
Istradefylline is used to address “off” episodes in adults with Parkinson’s disease. These episodes refer to times when standard medications, like levodopa/carbidopa, wear off, causing Parkinson’s symptoms such as tremor, rigidity, and difficulty moving to reappear or intensify. The medication is an adjunctive therapy, meaning it is taken in addition to a levodopa/carbidopa regimen.
The typical starting dosage is 20 mg taken orally once daily, which can be increased to a maximum of 40 mg once a day based on individual response and tolerability. Istradefylline can be taken with or without food, offering flexibility in administration. Clinical studies have shown that it can help reduce daily “off” time by approximately 0.75 to 0.82 hours.
Potential Side Effects
Istradefylline can lead to various side effects, which have been observed in clinical trials. A frequently reported adverse reaction is dyskinesia, which refers to uncontrolled, involuntary movements. The incidence of dyskinesia was higher in patients receiving istradefylline compared to those on placebo, with rates around 15% for 20 mg/day and 17% for 40 mg/day doses, versus 8% for placebo.
Other common effects include dizziness, constipation, and nausea. Some individuals have also reported experiencing hallucinations, which involve seeing or hearing things that are not present. Insomnia, or difficulty sleeping, is another reported side effect.
Important Safety Considerations
Important safety considerations accompany istradefylline use. There is a potential for new or worsened dyskinesia, which are involuntary movements. Patients should be monitored for these movements, as they can sometimes be difficult to differentiate from those caused by levodopa itself.
The medication may also lead to hallucinations and psychotic behaviors, such as unusual thoughts or confusion. Individuals with a history of major psychotic disorders generally should not receive istradefylline, and a dosage reduction or discontinuation may be considered if such behaviors develop. Furthermore, there is a possibility of developing impulse control disorders, which can manifest as urges like compulsive gambling, binge eating, or abnormal sexual behaviors.
Drug interactions also require attention. Strong inhibitors of the CYP3A4 enzyme can increase the concentration of istradefylline in the body, potentially requiring a maximum dose reduction to 20 mg daily. Conversely, strong CYP3A4 inducers should generally be avoided, as they can decrease the drug’s effectiveness. Tobacco smoking, specifically smoking 20 or more cigarettes per day, can also reduce istradefylline exposure, leading to a recommended increase to the 40 mg daily dose for these individuals.