Data from FDA - Curated by EPG Health - Last updated 28 September 2017

Indication(s)

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. 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)

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

ALP Lab Assessment

ALP Lab Assessment

Discover and overview of hypophosphatasia and details required to facilitate the timely and accurate detection of low alkaline phosphatase.

Acute and Advanced Heart Failure

Acute and Advanced Heart Failure

What are the most effective treatments for acute heart failure? Can you define advanced heart failure? Discover here...

+ 3 more

Allergic Rhinitis

Allergic Rhinitis

Allergic rhinitis causes great strain on the workforce. Help to reduce sick days and improve productivity with appropriate treatment options.

+ 4 more

Load more

Related Content

Advisory information

contraindications
4 CONTRAINDICATIONS GOCOVRI is contraindicated in patients with end stage renal disease (ie., creatinine clearance below 15 mL/min/1.73 m2) [see Clinical Pharmacology (12.3)]. GOCOVRI is contraindicated in patients with end stage renal disease (4)
Adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described in more detail elsewhere in the labeling: Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions (5.1)] Suicidality and Depression [see Warnings and Precautions (5.2)] Hallucinations/Psychotic Behavior [see Warnings and Precautions (5.3)] Dizziness and Orthostatic Hypotension [see Warnings and Precautions (5.4)] Withdrawal-Emergent Hyperpyrexia and Confusion [see Warnings and Precautions (5.5)] Impulse Control/Compulsive Behaviors [see Warnings and Precautions (5.6)] The most commonly observed adverse reactions occurring at a frequency of >10% and greater than placebo were hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Adamas Pharma, LLC at 1-833-223-2627 or FDA at 1-800-FDA-1088 or http://www.fda.gov/medwatch. 6.1. Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Placebo-Controlled Trials GOCOVRI was evaluated in two double-blind, placebo-controlled efficacy trials of similar design and population: Study 1 (123 patients) and Study 2 (75 patients). The study population was approximately 56% male and 94% white, with a mean age of 65 years (age range from 34 years to 82 years). The mean duration of levodopa-induced dyskinesia was 4 years (range 0.1 to 14 years). Active treatment started at 137 mg once daily for one week, followed by a dose increase to 274 mg once daily. The treatment duration was 25 weeks for Study 1 and 13 weeks for Study 2. Of the 100 patients in the safety population described below, 39 patients were treated with GOCOVRI for 24 weeks. The safety data for these trials were pooled. The most common adverse reactions reported in >10% of GOCOVRI-treated patients and more frequently than on placebo were: hallucination, dizziness, dry mouth, peripheral edema, constipation, falls, and orthostatic hypotension. The overall rate of discontinuation because of adverse reactions for GOCOVRI-treated patients was 20%, compared to 8% for placebo-treated patients. Adverse reactions that led to treatment discontinuation in at least 2% of patients were hallucination (8% GOCOVRI vs. 0% placebo), dry mouth (3% GOCOVRI vs. 0% placebo), peripheral edema (3% GOCOVRI vs. 0% placebo), blurred vision (GOCOVRI 3% vs. 0% placebo), postural dizziness and syncope (GOCOVRI 2% vs. 0% placebo), abnormal dreams (GOCOVRI 2% vs. 1% placebo), dysphagia (GOCOVRI 2% vs. 0% placebo), and gait disturbance (GOCOVRI 2% vs. 0% placebo). Table 1: Adverse Reactions Reported for ≥ 3% of Patients Treated with 274 mg GOCOVRI in Study 1 and Study 2 (Pooled Analysis) a=Includes visual hallucinations and auditory hallucinations b=Includes anxiety and generalized anxiety c=Includes orthostatic hypotension, postural dizziness, syncope, presyncope, and hypotension d=The denominator is all male patients in the safety population randomized to GOCOVRI (n=54) or placebo (n=57) Adverse Reactions GOCOVRI 274 mg N=100 % Placebo N=98 % Psychiatric disorders Hallucinationa 21 3 Anxietyb 7 3 Insomnia 7 2 Depression/Depressed mood 6 1 Abnormal dreams 4 2 Confusional state 3 2 Nervous system disorders Dizziness 16 1 Headache 6 4 Dystonia 3 1 Gastrointestinal disorders Dry mouth 16 1 Constipation 13 3 Nausea 8 3 Vomiting 3 0 General disorders and administration site conditions Peripheral edema 16 1 Gait disturbance 3 0 Injury, poisoning and procedural complications Fall 13 7 Contusion 6 1 Infections and infestations Urinary tract infection 10 5 Skin and subcutaneous tissue disorders Livedo reticularis 6 0 Pigmentation disorder 3 0 Metabolism and nutrition disorders Decreased appetite 6 1 Vascular disorders Orthostatic hypotensionc 13 1 Eye disorders Blurred vision 4 1 Cataract 3 1 Dry eye 3 0 Musculoskeletal and connective tissue disorders Joint swelling 3 0 Muscle spasms 3 0 Reproductive system and breast disorders Benign prostatic hyperplasiad 6 2 Respiratory, thoracic and mediastinal disorders Cough 3 0 Other clinically relevant adverse reactions observed at <3% included somnolence, fatigue, suicide ideation or attempt, apathy, delusions, illusions, and paranoia [see Warnings and Precautions (5.1, 5.2, 5.3)]. Difference in the Frequency of Adverse Reactions by Gender Adverse reactions reported more frequently in women treated with 274 mg of GOCOVRI (n=46), compared to men (n=54), were: dry mouth (22% women, 11% men), nausea (13% women, 4% men), livedo reticularis (13% women, 0% men), abnormal dreams (9% women, 0% men) and cataracts (7% women, 0% men). Men treated with 274 mg of GOCOVRI reported the following adverse reactions more frequently than women: dizziness (20% men, 11% women), peripheral edema (19% men, 11% women), anxiety (11% men, 2% women), orthostatic hypotension (7% men, 2% women) and gait disturbance (6% men, 0% women). Difference in the Frequency of Adverse Reactions by Age Hallucinations (visual or auditory) were reported in 31% of GOCOVRI-treated patients age 65 years and over (n=52), compared to 10% in patients below the age of 65 years (n=48). Falls were reported in 17% of GOCOVRI-treated patients age 65 and over, compared to 8% of patients below age 65. Orthostatic hypotension was reported in 8% of patients age 65 and over, compared to 2% of patients below age 65.

Usage information

Dosing 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. 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 m2) 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 m2) Initial dosage: 68.5 mg once daily at bedtime Maximum recommended dosage: 137 mg once daily at bedtime1 Severe renal impairment (15 to 29 mL/min/1.73 m2) 68.5 mg once daily at bedtime End Stage Renal Disease (below 15 mL/min/1.73 m2) 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 stop GOCOVRI in patients who have been on the drug for more than 4 weeks, their dose should typically, if possible, be reduced by half for their final week of dosing. If a dose of GOCOVRI is missed, the next dose should be taken as scheduled.
Use in special populations
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm (8.1) 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with use of amantadine in pregnant women. Animal studies suggest a potential risk for fetal harm with amantadine. In mice and rats, adverse developmental effects (embryolethality, increased incidence of malformations, and reduced fetal body weight) were observed when amantadine was administered to pregnant animals at clinically relevant doses [see Data]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk for major birth defects and miscarriage in patients with Parkinson’s disease is unknown. Data Animal Data The effects of amantadine on development have not been tested in studies conducted in animals using currently recommended methodology; however, developmental toxicity studies of amantadine have been reported in the published literature. In mice, oral administration of amantadine (0, 10, or 40 mg/kg/day) to pregnant animals during organogenesis (gestation days 7-12) resulted in embryolethality and reduced fetal body weight at the highest dose tested, which was associated with maternal toxicity. The no-effect dose for developmental toxicity in mice (10 mg/kg/day) is less than the recommended human dose (RHD) of 274 mg/day, based on body surface area (mg/m2). In rats, oral administration of amantadine (0, 40 or 120 mg/kg/day) to pregnant animals during organogenesis (gestation days 7-12) resulted in embryolethality and reduced fetal body weight at the highest dose. The no-effect dose for developmental toxicity in this study (40 mg/kg/day) is approximately equal to the RHD on a mg/m2 basis. In another study in pregnant rats, oral administration of amantadine during organogenesis (gestation days 7-14) resulted in an increase in visceral and skeletal malformations at oral doses of 50 and 100 mg/kg/day. The no-effect dose for teratogenicity in this study (37 mg/kg/day) is approximately equal to the RHD on a mg/m2 basis. Evaluation of parturition, lactation, and post-natal development in a limited number of litters from the mouse and rat studies described above revealed reductions in live litter size and pup weights at birth at 40 mg/kg/day in mice and 120 mg/kg/day in rats. 8.2 Lactation Risk Summary Amantadine is excreted into human milk, but amounts have not been quantified. There is no information on the risk to a breastfed infant. Amantadine may alter breast milk production or excretion [see Data]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for GOCOVRI and any potential adverse effects on the breastfed infant from GOCOVRI or from the underlying maternal condition. Data In published studies, amantadine reduced serum prolactin levels and the symptoms of galactorrhea in patients taking neuroleptic drugs. The effect of amantadine on milk supply has not been evaluated in nursing mothers. 8.4 Pediatric Use The safety and effectiveness of GOCOVRI in pediatric patients have not been established. 8.5 Geriatric Use The majority of people with Parkinson’s disease are 65 years and older. In Phase 3 clinical trials, the mean age of patients at study entry was 65 years. Of the total number of patients in clinical studies of GOCOVRI, 46% were less than 65 years of age, 39% were 65-74 years of age, and 15% were 75 years of age or older. Hallucinations and falls occurred more frequently in patients 65 years of age or older, compared to those less than 65 years of age [see Adverse Reactions (6.1)]. No dose adjustment is recommended on the basis of age. GOCOVRI is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see Dosage and Administration (2.3)]. 8.6. Renal Impairment GOCOVRI is contraindicated for use in patients with end-stage renal disease (creatinine clearance lower than 15 mL/min/1.73 m2). For patients with moderate renal impairment (creatinine clearance between 30 and 59 mL/min/1.73 m2), a 50% dose reduction of GOCOVRI dosage to a starting daily dose of 68.5 mg daily at bedtime for a week, to a maximum dosage of 137 mg daily at bedtime is recommended. For patients with severe renal impairment (creatinine clearance between 15 and 29 mL/min/1.73 m2), a daily dose of 68.5 mg at bedtime is the recommended initial and maximum dosage [see Dosage and Administration (2.3)]. Creatinine clearance values are estimated by the Modification of Diet in Renal Disease (MDRD) method.

Interactions

7 DRUG INTERACTIONS Other Anticholinergic Drugs: Doses should be reduced if atropine-like effects occur (7.1) Drugs Affecting Urinary pH: Excretion increases with acidic urine; possible accumulation with urine change towards alkaline (7.2) Live Attenuated Influenza Vaccines: Not recommended during use (7.3) Alcohol: Concomitant use not recommended (7.4) 7.1 Other Anticholinergic Drugs Products with anticholinergic properties may potentiate the anticholinergic-like side effects of amantadine. The dose of anticholinergic drugs or of GOCOVRI should be reduced if atropine-like effects appear when these drugs are used concurrently. 7.2 Drugs Affecting Urinary pH The pH of the urine has been reported to influence the excretion rate of amantadine. Urine pH is altered by diet, drugs (e.g., carbonic anhydrase inhibitors, sodium bicarbonate), and clinical state of the patient (e.g., renal tubular acidosis or severe infections of the urinary tract). Since the excretion rate of amantadine increases rapidly when the urine is acidic, the administration of urine acidifying drugs may increase the elimination of the drug from the body. Alterations of urine pH towards the alkaline condition may lead to an accumulation of the drug with a possible increase in adverse reactions. Monitor for efficacy or adverse reactions under conditions that alter the urine pH to more acidic or alkaline, respectively. 7.3 Live Attenuated Influenza Vaccines Because of its antiviral properties, amantadine may interfere with the efficacy of live attenuated influenza vaccines. Therefore, live vaccines are not recommended during treatment with GOCOVRI. Inactivated influenza vaccines may be used, as appropriate. 7.4 Alcohol Concomitant use with alcohol is not recommended, as it may increase the potential for CNS effects such as dizziness, confusion, lightheadedness, and orthostatic hypotension [see Warnings and Precautions (5.4)], and may result in dose-dumping [see Clinical Pharmacology (12.3)].

More information

Category Value
Authorisation number NDA208944
Agency product number BF4C9Z1J53
Orphan designation No
Product NDC 70482-170,70482-085
Date Last Revised 07-09-2017
Type HUMAN PRESCRIPTION DRUG
RXCUI 1944382
Storage and handling 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Marketing authorisation holder Adamas Pharma, LLC