Amantadine Extended Release Capsules, for Oral Use

Dosage Forms And Strengths

GOCOVRI is available as extended release capsules for oral administration. Each capsule contains 68.5 mg or 137 mg of amantadine.

The 68.5 mg capsule is a white opaque size #2 capsule, with black printing of ‘ADAMAS’ on front and ‘85’ on back of the cap and three black bands printed on body of capsule. The 137 mg capsule is a light blue opaque size #0 capsule, with black printing of ‘ADAMAS’ on front and ‘170’ on back of the cap and three black bands printed on body of capsule.

GOCOVRI is supplied as extended release capsules in the following configurations:

The 68.5 mg capsule is a white opaque size #2 capsule, with black printing of ‘ADAMAS’ on front and ‘85’ on back of the cap and three black bands printed on body of capsule.

• 60 count bottles NDC# 70482-085-60

The 137 mg capsule is a light blue opaque size #0 capsule, with black printing of ‘ADAMAS’ on front and ‘170’ on back of the cap and three black bands printed on body of capsule.

• 60 count bottles NDC# 70482-170-60

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].

Manufactured for: Adamas Pharma LLC. Emeryville, CA 94608. Revised: Aug 2017

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]
• Suicidality and Depression [see WARNINGS AND PRECAUTIONS]
• Hallucinations/Psychotic Behavior [see WARNINGS AND PRECAUTIONS]
• Dizziness and Orthostatic Hypotension [see WARNINGS AND PRECAUTIONS]
• Withdrawal-Emergent Hyperpyrexia and Confusion [see WARNINGS AND PRECAUTIONS]
• Impulse Control/Compulsive Behaviors [see WARNINGS AND PRECAUTIONS]

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.

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)

Other clinically relevant adverse reactions observed at <3% included somnolence, fatigue, suicide ideation or attempt, apathy, delusions, illusions, and paranoia [see WARNINGS AND PRECAUTIONS].

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 in (7% men, 2% women) and gait disturbance (6% men, 0% women).

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.

Included as part of the "PRECAUTIONS" Section

Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 1 gram of amantadine hydrochloride (equivalent to 0.8 g amantadine). Acute toxicity may be attributable to the anticholinergic effects of amantadine. Drug overdose has resulted in cardiac, respiratory, renal, or central nervous system toxicity. Pulmonary edema and respiratory distress (including adult respiratory distress syndrome, ARDS) have been reported with amantadine; renal dysfunction, including increased BUN and decreased creatinine clearance, can occur.

Central nervous system effects that have been reported with overdose include agitation, aggressive behavior, hypertonia, hyperkinesia, ataxia, tremor, disorientation, depersonalization, fear, delirium, psychotic reactions, lethargy, and coma. Seizures may be exacerbated in patients with prior history of seizure disorders. Hyperthermia has occurred with amantadine overdose.

For acute overdosing, general supportive measures should be employed along with immediate gastric decontamination if appropriate. Give intravenous fluids if necessary. The excretion rate of amantadine increases with acidification of urine, which may increase the elimination of the drug. Monitor patients for arrhythmias and hypotension. Electrocardiographic monitoring may be needed after ingestion because arrhythmias have been reported after overdose, including arrhythmias with fatal outcomes. Adrenergic agents, such as isoproterenol, in patients with an amantadine overdose has been reported to induce arrhythmias.

Monitor blood electrolytes, urine pH, and urinary output. Although amantadine is not efficiently removed by hemodialysis, this procedure may be useful in the treatment of amantadine toxicity in patients with renal failure.

GOCOVRI
(goh-KUV-ree)
(amantadine) Extended Release Capsules, for Oral Use

What is GOCOVRI?

GOCOVRI is a prescription medicine used for the treatment of:

• dyskinesia (sudden uncontrolled movements) in people with Parkinson’s disease who are treated with levodopa therapy or levodopa therapy with other medicines that increase the effects of dopamine in the brain.

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

Do not take GOCOVRI if you have severe kidney problems

Before you take GOCOVRI, tell your doctor about all of your medical conditions, including if you:

• have kidney problems.
• have daytime sleepiness from a sleep disorder, have unexpected or unpredictable sleepiness or periods of sleep, take a medicine to help you sleep, or take any medicine that makes your drowsy.
• have mental problems, such as suicidal thoughts, depression, or hallucinations.
• have unusual urges including gambling, increased sex drive, compulsive eating, or compulsive shopping.
• drink alcoholic beverages. This may increase your chances of becoming drowsy or sleepy while taking GOCOVRI.
• are pregnant or plan to become pregnant. GOCOVRI may harm your unborn baby.
• are breastfeeding or plan to breastfeed. GOCOVRI can pass into your breastmilk. Talk to your doctor about the best way to feed your baby if you take GOCOVRI.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Especially tell your doctor if you:

• take medicines like sodium bicarbonate.
• have had or are planning to have a live flu (influenza) vaccination (nasal spray). You can receive the influenza vaccination shot but should not get a live influenza vaccine while taking GOCOVRI.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take GOCOVRI?

• Take GOCOVRI as exactly as your doctor tells you to.
• Start GOCOVRI with 1 capsule at bedtime. Your doctor may change your dose if needed. If your doctor tells you to take 2 capsules, take them together at bedtime.
• Do not stop or change GOCOVRI before talking with your doctor. Call your doctor if you have symptoms of withdrawal such as fever, confusion, or severe muscle stiffness.
• GOCOVRI may be taken with food or without food.
• Swallow GOCOVRI capsules whole. Do not crush, chew, or divide.
• GOCOVRI capsules may be opened and sprinkled on applesauce before swallowing. Sprinkle all of the medicine in the capsule on the applesauce. Take all of the medicine right away without chewing.
• If you miss a dose of GOCOVRI, do not take an extra dose. Take your usual dose of GOCOVRI on the next day at bedtime.
• If you have forgotten to take GOCOVRI for several days, contact your doctor.
• Do not drink alcohol with your dose of GOCOVRI.
• Do not use GOCOVRI capsules that are damaged or show signs of tampering.
• If you take too much GOCOVRI, call your doctor or go to the nearest hospital emergency room right away.

What should I avoid while taking GOCOVRI?

• Do not drive, operate machinery, or do other dangerous activities until you know how GOCOVRI affects you.
• Do not drink alcohol while taking GOCOVRI. It can increase your chances of getting serious side effects.

What are the possible side effects of GOCOVRI?

GOCOVRI may cause serious side effects, including:

• falling asleep during normal activities. You may fall asleep while doing normal activities such as driving a car, talking, or eating while taking GOCOVRI or other medicines that treat Parkinson’s disease. You may fall asleep without being drowsy or without warning. This may result in having accidents. Your chances of falling asleep while doing normal activities while taking GOCOVRI are greater if you take other medicines that cause drowsiness. Tell your doctor right away if this happens.
• suicidal thoughts or actions and depression. Some people taking GOCOVRI have had suicidal thoughts, attempted suicide, or depression. Tell your doctor if you have new or sudden changes in mood, behaviors, thoughts, or feelings, including thoughts about hurting yourself or ending your life.
• hallucinations. GOCOVRI can cause or worsen hallucinations (seeing or hearing things that are not real) or psychotic behavior. Contact your doctor if you have hallucinations.
• feeling dizzy, faint or light headed, especially when you stand up (orthostatic hypotension). Light headedness or fainting may happen when getting up too quickly from a sitting or lying position especially after long periods of time, when first starting GOCOVRI, or if your dose has been increased. Contact your doctor if you become light headed or faint when standing up.
• unusual urges. Some people taking GOCOVRI get urges to behave in a way unusual for them. Examples of this are an unusual urge to gamble, increased sexual urges, strong urges to spend money, binge eating and the inability to control these urges. If you notice or your family notices that you are developing any unusual behaviors, talk to your doctor.

The most common side effects of GOCOVRI include dry mouth, swelling of legs and feet, constipation, and falls.

These are not all the possible side effects of GOCOVRI. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store GOCOVRI?

• Store GOCOVRI at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep GOCOVRI out of the reach of children.

General information about the safe and effective use of GOCOVRI.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use GOCOVRI for a condition for which it was not prescribed. Do not give GOCOVRI to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or doctor for information about GOCOVRI that is written for health professionals.

What are the ingredients in GOCOVRI?

Active ingredient: amantadine hydrochloride

Inactive ingredients: copovidone, ethylcellulose, hypromellose, magnesium stearate, medium chain triglycerides, microcrystalline cellulose, povidone, and talc

This Patient Information has been approved by the U.S. Food and Drug Administration