GOCOVRI

Clinical summary

Indications and usage 1 INDICATIONS AND USAGE GOCOVRI ® is indicated: For the treatment of dyskinesia in patients with Parkinson's disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications As adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes GOCOVRI ® is indicated: For the treatment of dyskinesia in patients with Parkinson's disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications ( 1 ) As adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes ( 1 ) Dosage and administration 2 DOSAGE AND ADMINISTRATION Administer orally once daily at bedtime ( 2.1 , 2.3 ) The initial daily dosage is 137 mg; after 1 week, increase to the recommended daily dosage of 274 mg ( 2.1 ) Swallow whole; may sprinkle contents on soft food ( 2.2 ) May be taken with or without food; avoid use with alcohol ( 2.2 ) A lower dosage is recommended for patients with moderate or severe renal impairment ( 2.3 ) 2.1 Dosing Information The initial daily dosage of GOCOVRI is 137 mg, administered orally once daily at bedtime. After one week, increase to the recommended dosage of 274 mg (two 137 mg capsules) once daily at bedtime. GOCOVRI is not substitutable with other amantadine immediate- or extended-release products. 2.2 Administration Information GOCOVRI should be swallowed whole. Do not crush, chew or divide capsules. If needed, GOCOVRI may be administered by carefully opening and sprinkling the entire contents on a small amount (teaspoonful) of soft food, such as applesauce. The drug/food mixture should be swallowed immediately without chewing. Do not store mixture for future use. GOCOVRI can be taken with or without food [see Clinical Pharmacology ( 12.3 )]. Concomitant use of GOCOVRI with alcohol is not recommended [see Drug Interactions ( 7.4 )]. It is recommended to avoid sudden discontinuation of GOCOVRI [see Dosage and Administration ( 2.4 )]. 2.3 Dosing in Patients with Renal Impairment The initial and maximum recommended daily dosage of GOCOVRI for patients with renal impairment (creatinine clearance estimated by Modification of Diet in Renal Disease (MDRD) method) is provided below. 1 Increase, if needed, after one week of the initial dosage Creatinine Clearance Dosage Mild renal impairment (60 to 89 mL/min/1.73 m 2 ) Initial dosage: 137 mg once daily at bedtime. After one week, increase to recommended dosage of 274 mg once daily at bedtime. Moderate renal impairment (30 to 59 mL/min/1.73 m 2 ) Initial dosage: 68.5 mg once daily at bedtime Maximum recommended dosage: 137 mg once daily at bedtime 1 Severe renal impairment (15 to 29 mL/min/1.73 m 2 ) 68.5 mg once daily at bedtime End Stage Renal Disease (below 15 mL/min/1.73 m 2 ) Contraindicated 2.4 Discontinuation and Missed Dose Rapid dose reduction or withdrawal of GOCOVRI may cause adverse reactions [see Warnings and Precautions ( 5.5 )]. Therefore, to discontinue GOCOVRI in patients who have been on the drug for more than 4 weeks, GOCOVRI dosage should, if possible, be reduced by half for the final week of dosing. If a dose of GOCOVRI is missed, the next dose should be taken as scheduled. Warnings and cautions 5 WARNINGS AND PRECAUTIONS Falling Asleep During Activities of Daily Living : Advise patients prior to treatment; ordinarily discontinue if occurs ( 5.1 ) Suicidality and Depression : Monitor patients for depressed mood, depression, or suicidal ideation or behavior ( 5.2 ) Hallucinations/Psychotic Behavior: Patients with major psychotic disorder should ordinarily not be treated with GOCOVRI; observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases ( 5.3 ) Dizziness and Orthostatic Hypotension : Monitor patients for dizziness and orthostatic hypotension, especially after starting GOCOVRI or increasing the dose ( 5.4 ) Withdrawal-Emergent Hyperpyrexia and Confusion : Avoid sudden discontinuation ( 5.5 ) Corneal Edema : Monitor patients for new changes in vision, including blurred vision, with or without eye pain, or vision loss. Taper and discontinue if corneal edema occurs ( 5.6 ) Impulse Control/Compulsive Behaviors : Ask patients about increased gambling urges, sexual urges, uncontrolled spending or other urges; consider dose reduction or discontinuation if occurs ( 5.7 ) 5.1 Falling Asleep During Activities of Daily Living and Somnolence Patients treated for Parkinson's disease have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes has resulted in accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. In controlled clinical trials, somnolence and fatigue were reported as adverse reactions in 4% of patients treated with GOCOVRI 274 mg and 1% for placebo.