Rasagiline

Indications

Rasagiline is used for: Parkinson Disease

Adult Dose

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 Hepatic impairment Mild (Child-Pugh A): Not to exceed 0.5 mg/day Moderate-to-severe (Child-Pugh B/C): Do not use

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment: No dosage adjustment required for mild-to-moderate; not studied in severe

Administration

May be taken with or without food. Avoid tyramine-rich foods, beverages or dietary supplements & amines (from cough/cold prep).

Contra Indications

Severe hepatic impairment. Concomitant use w/ other MAOIs and pethidine w/in 14 days after discontinuation of therapy; St John's wort.

Precautions

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 Lactation There are no data on presence of drug in human milk or effects on breastfed infant; in rats, rasagiline was shown to inhibit prolactin secretion; the clinical relevance in humans is unknown, and there are no data on effects of rasagiline on prolactin secretion in humans The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and potential adverse effects on breastfed infant from drug or from underlying maternal condition

Pregnancy-Lactation

Pregnancy There are no adequate data on developmental risks associated with use in pregnant women; in animal studies, oral administration to rats during gestation and lactation resulted in decreased survival and reduced body weight in offspring at doses similar to those used clinically; when administered to pregnant animals in combination with levodopa/carbidopa, there were increased incidences of fetal skeletal variations in rats and increases in embryofetal death and cardiovascular abnormalities in rabbits Lactation There are no data on presence of drug in human milk or effects on breastfed infant; in rats, rasagiline was shown to inhibit prolactin secretion; the clinical relevance in humans is unknown, and there are no data on effects of rasagiline on prolactin secretion in humans The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and potential adverse effects on breastfed infant from drug or from underlying maternal condition

Interactions

Increased plasma levels w/ potent CYP1A2 inhibitors (e.g. ciprofloxacin). Increased clearance w/ entacapone. Potentially Fatal: Increased risk of non-selective MAO inhibition w/ other MAOIs and pethidine that may lead to hypertensive crises.

Adverse Effects

Side effects of Rasagiline : >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% CV MI Bundle branch block Gastrointestinal hemorrhage

Mechanism of Action

Rasagiline is a potent, irreversible monoamine oxidase (MAO)-B selective inhibitor which may cause an increase in extracellular levels of dopamine in the striatum, leading to reduced symptomatic motor deficits of Parkinson's disease.