Adverse reactions: Pooled Study 1 and Study 21

Adverse Reactions (≥3%) PLACEBO
n = 98
%
GOCOVRI® 274 mg
n = 100
%
Psychiatric disorders
Hallucinationa 3 21
Anxietyb 3 7
Insomnia 2 7
Depression/depressed mood 1 6
Abnormal dreams 2 4
Confusional state 2 3
Nervous system disorders
Dizziness 1 16
Headache 4 6
Dystonia 1 3
Gastrointestinal disorders
Dry mouth 1 16
Constipation 3 13
Nausea 3 8
Vomiting 0 3
General disorders and administration site conditions
Peripheral edema 1 16
Gait disturbance 0 3
Injury, poisoning, and procedural complications
Fall 7 13
Contusion 1 6
Infections and infestations
Urinary tract infection 5 10
Skin and subcutaneous tissue disorders
Livedo reticularis 0 6
Pigmentation disorder 0 3
Metabolism and nutrition disorders
Decreased appetite 1 6
Vascular disorders
Orthostatic hypotensionc 1 13
Eye disorders
Blurred vision 1 4
Cataract 1 3
Dry eye 0 3
Musculoskeletal and connective tissue disorders
Joint swelling 0 3
Muscle spasms 0 3
Reproductive system and breast disorders
Benign prostatic hyperplasiad 2 6
Respiratory, thoracic, and mediastinal disorders
Cough 0 3

ARs, adverse reactions.

Other clinically relevant ARs observed at <3% included somnolence, fatigue, suicide ideation or attempt, apathy, delusions, illusions, and paranoia.

If your patient reports any adverse reactions, you should report them to the FDA at 1-800-FDA-1088 or fda.gov/medwatch.

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).

Most hallucinations were rated as mild and the majority (86%) were fully resolved

HALLUCINATIONS (POOLED SAFETY DATA)1-3

HALLUCINATIONS
21/100 (21%)

Investigator rating:

  • 13 (62%) as mild
  • 6 (29%) as moderate
  • 2 (10%) as severe

Resolution of hallucinations:

  • 18 (86%) fully resolved
  • 12 (57%) resolved in ≤2 weeks
  • 0 (0%) required hospitalization or
    treatment with antipsychotics
  • Patients <65 years old: 5/48 (10%)2
  • Patients ≥65 years old: 16/52 (31%)2
  • Majority of patients with PD are elderly and are more likely to have decreased renal function, which may put these patients at greater risk of adverse effects1
  • Care should be taken in dose selection; observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases1

Pooled ARs leading to treatment discontinuations1

The overall pooled rate of discontinuation in at least 2% of patients due to ARs for patients treated with placebo was 8% vs 20% with GOCOVRI®1

ADVERSE REACTIONS GOCOVRI® 274 mg
n = 100
%
Placebo
n = 98
%
Hallucination 8 0
Dry mouth 3 0
Insomnia 7 2
Peripheral edema 3 0
Blurred vision 3 0
Postural dizziness and syncope 2 0
Abnormal dreams 2 1
Dysphagia 2 0
Gait disturbance 2 0
In the EASE-LID 2 OLE study

The safety profile of GOCOVRI® in this long-term study remained consistent with the pivotal trials4

ADVERSE EVENTS AND DISCONTINUATIONS DUE TO ADVERSE EVENTS (SAFETY POPULATION)

ADVERSE EVENTS CONTINUING GOCOVRI®
(n = 60)
PREVIOUS PLACEBO
(n = 78)
ALL PATIENTS
(N = 223)
Summary
Any AE 57 (95.0%) 70 (89.7%) 205 (91.9%)
Study-drug related 31 (51.7%) 45 (57.7%) 124 (55.6%)
Any SAE 16 (26.7%) 21 (26.9%) 60 (26.9%)
Study-drug related 1 (1.7%) 3 (3.8%) 5 (2.2%)
Any leading to study-drug discontinuation or death 12 (20.0%) 21 (26.9%) 49 (22.0%)
Study-drug related 4 (6.7%) 15 (19.2%) 31 (13.9%)
By preferred term*
Fall 13 (21.7%) 29 (37.2%) 73 (32.7%)
Hallucination 15 (25.0%) 24 (30.8%) 54 (24.2%)
Visual 14 (23.3%) 24 (30.8%) 52 (23.3%)
Auditory 1 (1.7%) 1 (1.3%) 5 (2.2%)
Peripheral edema 10 (16.7%) 12 (15.4%) 36 (16.1%)
Constipation 9 (15.0%) 12 (15.4%) 30 (13.5%)
Urinary tract infection 7 (11.7%) 8 (10.3%) 23 (10.3%)
Dizziness 4 (6.7%) 10 (12.8%) 22 (9.9%)
Nausea 7 (11.7%) 8 (10.3%) 22 (9.9%)
Insomnia 8 (13.3%) 5 (6.4%) 21 (9.4%)
Livedo reticularis 6 (10.0%) 5 (6.4%) 20 (9.0%)
ON and OFF phenomenon 7 (11.7%) 4 (5.1%) 18 (8.1%)
Dry mouth 4 (6.7%) 6 (7.7%) 17 (7.6%)
* Includes all preferred terms with an incidence ≥7.5% among all patients.
AE, adverse event; SAE, serious adverse event.
  • Discontinuations due to adverse events occurred more frequently among patients initiating GOCOVRI® in this study, compared to those who continued on GOCOVRI® from phase 3 trials4
  • Discontinuations tended to occur in the first weeks of treatment around dose initiation and titration4
  • No new safety signals were observed in this open-label extension4

INDICATION and important safety information

GOCOVRI® (amantadine) extended release capsules 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

It is not known if GOCOVRI is safe and effective in children.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS
GOCOVRI is contraindicated in patients with creatinine clearance below 15 mL/min/1.73 m2.

WARNINGS AND PRECAUTIONS

Falling Asleep During Activities of Daily Living and Somnolence: Patients treated with Parkinson’s disease medications have reported falling asleep during activities of daily living. If a patient develops daytime sleepiness during activities that require full attention (e.g., driving a motor vehicle, conversations, eating), GOCOVRI should ordinarily be discontinued or the patient should be advised to avoid potentially dangerous activities.

Suicidality and Depression: Monitor patients for depression, including suicidal ideation or behavior. Prescribers should consider whether the benefits outweigh the risks of treatment with GOCOVRI in patients with a history of suicidality or depression.

Hallucinations/Psychotic Behavior: Patients with a major psychotic disorder should ordinarily not be treated with GOCOVRI because of the risk of exacerbating psychosis. Observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases.

Dizziness and Orthostatic Hypotension: Monitor patients for dizziness and orthostatic hypotension, especially after starting GOCOVRI or increasing the dose.

Withdrawal-Emergent Hyperpyrexia and Confusion: Rapid dose reduction or abrupt discontinuation of GOCOVRI, may cause an increase in the symptoms of Parkinson’s disease or cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, or slurred speech. Avoid sudden discontinuation of GOCOVRI.

Impulse Control/Compulsive Behaviors: Patients may experience urges (e.g. gambling, sexual, money spending, binge eating) and the inability to control them. It is important for prescribers to ask patients or their caregivers about the development of new or increased urges. Consider dose reduction or stopping medications.

ADVERSE REACTIONS
The most common adverse reactions (>10%) were hallucination, dizziness, dry mouth, peripheral edema, constipation, fall, and orthostatic hypotension.

View the full Prescribing Information.

References:
  1. GOCOVRI® (amantadine) [Prescribing Information]. Emeryville, CA. Adamas Pharma LLC; 2021.
  2. Elmer LW, Juncos JL, Singer C, et al. Pooled analyses of phase III studies of ADS-5102 (amantadine) extended-release capsules for dyskinesia in Parkinson’s disease. CNS Drugs. 2018;32(4):387-398.
  3. Data on file. Adamas Pharma LLC, Emeryville, CA.
  4. Tanner CM, Pahwa R, Hauser RA, et al. EASE LID 2: a 2-year open-label trial of Gocovri (amantadine) extended release for dyskinesia in Parkinson’s disease. J Parkinsons Dis. 2020;10(2):543–558.