Istradefylline (Nourianz) acts as an adenosine receptor inhibitor. It is used for Parkinson's disease patients who experience the "off" effects.

Istradefylline (Nourianz) Uses:

• Parkinson disease, "off" episode:

  • Metabolite I [norketamine] is N-dealkylated in the liver, where the cyclohexone ring is hydroxylated in metabolites III and IV, conjugated with glucuronic acid, and dehydrated to produce cyclohexene derivative (metabolite II).

Istradefylline (Nourianz) Dose in Adults:

Istradefylline (Nourianz) Dose in the treatment of Parkinson disease, "off" episode:

• 20 mg orally once a day;
• Depending on the patient's response and tolerance, the dose may be increased further up to the maximum amount of 40 mg once daily.

• Dosage adjustment for concomitant CYP3A4 inhibitors/inducers and tobacco smoking:

  • Dosage adjustment for concomitant therapy with strong CYP3A4 inducers:
    • Avoid use.
  • Dosage adjustment for concomitant therapy with strong CYP3A4 inhibitors:
    • 20 mg once a day
    • Do not exceed the maximum dose of 20 mg once a day.
  • Dosage adjustment for concomitant tobacco smoking (≥20 cigarettes/day or the equivalent amount of another tobacco product):
    • 40 mg once a day.

Use in Children:

Not indicated.

Pregnancy Risk Category: N (Not assigned)

• Studies on animal reproduction have shown that in utero exposure to the drug can cause harm to fetuses.
• It is important that women undergoing treatment are advised to use effective contraception.

Use while breastfeeding

• The drug's potential for excretion into breastmilk is unknown.
• The manufacturer advises evaluating the advantages and disadvantages of medication therapy for the expectant mother with any possible risks to the baby.

Istradefylline (Nourianz) Dose in Kidney Disease:

• CrCl ≥15 mL/minute:
  • Adjustment in the dose is not necessary.
• CrCl <15 mL/minute:
  • Patients with a CrCl of less than 15 ml/minute have not been investigated for it.
• End-stage renal disease requiring hemodialysis:
  • Not studied in patients on hemodialysis.

Istradefylline (Nourianz) Dose in Liver disease:

• Mild hepatic impairment (Child-Pugh class A):
  • Adjustment in the dose is not necessary.
• Moderate hepatic impairment (Child-Pugh class B):
  • 20 mg once a day to the maximum dose of 20 mg/day.
• Severe hepatic impairment (Child-Pugh class C):
  • Avoid use.
  • Not studied in severe hepatic impairment.

Side Effects of Istradefylline (Nourianz):

• Neuromuscular & skeletal:

  • Dyskinesia

Less Common Side Effects of Istradefylline (Nourianz):

• Central Nervous System:

  • Insomnia
  • Dizziness
  • Auditory Hallucination
  • Hallucination
  • Visual Hallucination
  • Abnormal Behavior
  • Abnormality In Thinking
  • Aggressive Behavior
  • Agitation
  • Confusion
  • Delirium
  • Delusion
  • Disorientation
  • Mania
  • Paranoid Ideation

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Increased Serum Glucose

• Gastrointestinal:

  • Constipation
  • Diarrhea
  • Decreased Appetite
  • Nausea

• Hepatic:

  • Increased Serum Alkaline Phosphatase

• Renal:

  • Increased Blood Urea Nitrogen

• Respiratory:

  • Upper Respiratory Tract Inflammation

Contraindications to Istradefylline (Nourianz):

• The manufacturer's labeling does not contain any contraindications.

Warnings and precautions

• Dyskinesias

  • Patients with dyskinesia should not use it. It can exacerbate or cause dyskinesias.

• Disorders of impulse control:

  • Patients who have used the drug have shown compulsive behavior or loss of impulse control.
  • These behaviors can manifest as an increase in libido or compulsive purchasing, binge eating, or pathological gambling.
  • These compulsive behaviors can be reversed by discontinuing treatment or decreasing the dosage.

• Psychotic effects

  • Treatment may cause mental and behavioral changes, or worsen a preexisting disorder.
  • Psychosis can manifest as paranoid thoughttion, hallucinations and delusions, disorientation or confusion, psychotic-like behaviors, aggressive behavior, agitation and delirium.
  • Treatment initiation and/or an increase in dose may cause mental status changes.
  • Patients with major psychotic disorders should not be treated.

• Hepatic impairment

  • Hepatic impairment patients should use the medication cautiously.
  • The maximum dosage should be decreased for those suffering from moderate hepatic impairment.
  • Patients with severe hepatic impairment shouldn't use the medication.
  • Patients with significant hepatic impairment have not been tested for it.

Istradefylline: Drug Interaction

Monitoring parameters:

• Mental status and behavioral changes;
• dyskinesias.

How to administer Istradefylline (Nourianz)?

It may be taken orally with or without food.

Mechanism of action of Istradefylline (Nourianz):

It is not clear what the drug does. It has been shown to be an antagonist of the adenosine-A receptor in animal studies.

Protein binding:

• About 98%

Metabolism:

• Primarily via CYP1A1 and CYP3A4, with minor contribution from CYP1A2, 2B6, 2C8, CYP2C9, CYP2C18, and 2D6

Half-life elimination:

• About 83 hours

Time to peak:

• Median: 3 to 4 hours

Excretion:

• Feces: ~48%;
• urine: 39%

International Brand Names of Istradefylline:

• Nourianz
• Nouriast

Istradefylline Brand Names in Pakistan:

No Brands Available in Pakistan.