Dosing and uses of Azilect (rasagiline)
Adult dosage forms and strengths
tablet
- 0.5mg
- 1mg
Parkinson Disease
Monotherapy: 1 mg PO qDay
Adjunct without levodopa: 1 mg PO qDay
Adjunct to levodopa: 0.5 mg PO qDay initially, may increase to 1 mg/day if needed and tolerated; consider reducing levodopa dose
Dosage modifications
Coadministration with CYP1A2 inhibitors (eg, ciprofloxacin): Not to exceed 0.5 mg/day
Renal impairment: No dosage adjustment required for mild-to-moderate; not studied in severe
Hepatic impairment
- Mild (Child-Pugh A): Not to exceed 0.5 mg/day
- Moderate-to-severe (Child-Pugh B/C): Do not use
Dosing Considerations
Do not exceed recommended doses because of risk for hypertension
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Azilect (rasagiline) adverse (side) effects
>10%
EPS (dyskinesia/dystonia) (18%)
Headache (14%)
Nausea (10-12%)
1-10%
Postural hypotension (6-9%)
Constipation (4-9%)
Weight loss (2-9%)
Arthralgia (7%)
Dyspepsia (7%)
Xerostomia (2-6%)
Depression (5%)
Fall (5%)
Flu-like syndrome (5%)
Hallucination (4-5%)
Conjunctivitis (3%)
Fever (3%)
Gastroenteritis (3%)
Rhinitis (3%)
Arthritis (2%)
Bruising (2%)
Malaise (2%)
Neck pain (2%)
Parasthesia (2%)
Vertigo (2%)
<1%
CVA
MI
Bundle branch block
Gastrointestinal hemorrhage
Warnings
Contraindications
Coadministration with meperidine, tramadol, methadone, and MAOIs, including other selective MAO-B inhibitors increases risk of serotonin syndrome; at least 14 days should elapse between discontinuation of rasagiline and initiation of treatment with these medications
Coadministration with St. John’s wort and with cyclobenzaprine
Coadministration with dextromethorphan because of risk of episode of psychosis or bizarre behavior
Cautions
May cause hypertension (including severe hypertensive syndromes) at recommended doses
May exacerbate hypertension; antihypertensive drugs may require dosage adjustment
May cause hypotension, especially orthostatic
May cause serotonin syndrome when used with antidepressants
Daytime drowsiness and somnolence reported during activities of daily living
May cause or exacerbate dyskinesia; decreasing the levodopa dose may lessen or eliminate this side effect
Hallucinations and psychotic-like behavior reported
Impulse control/compulsive behaviors reported; case reports describe patients with intense urges to gamble, increased sexual urges, intense urges to spend money, or binge eat
Withdrawal-emergent hyperpyrexia and confusion reported with rapid dose reduction of drugs that increase central dopaminergic tone; this is characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability
Patients with Parkinson disease have a higher risk (2 to 6-fold higher) of developing melanoma than the general population; unclear if this is due to the disease or other factors (eg, drug therapy); monitor for melanomas frequently and on a regular basis
Pregnancy and lactation
Pregnancy category: C
Lactation: may inhibit lactation; use caution
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Azilect (rasagiline)
Mechanism of action
Monoamine oxidase inhibitor, selective Type-B; inhibits dopamine depletion in striatal region of the brain, which in turn reduces symptomatic motor deficits of Parkinson's disease
Absorption
Peak Plasma Time: 1 hr
Onset of action: Within 1 hr
Bioavailability: 36%
Distribution
Protein Bound: 88-94%
Vd: 87 L
Metabolism
Via liver, primarily CYP1A2 (in vitro data)
Metabolites: 1-aminoindan, 3-hydroxy-N-propargyl-1-aminoindan, 3-hydroxy-1-aminoindan
Elimination
Half-life: 1.3-3 hr
Excretion: 62% urine; 7% feces
