GOCOVRI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for GOCOVRI (GOCOVRI).

How it works

GOCOVRI (amantadine) is an NMDA receptor antagonist that modulates glutamate-mediated excitotoxicity and increases dopamine release by inhibiting the vesicular monoamine transporter 2 (VMAT2) and potentiating dopaminergic function. It also has anticholinergic properties.

What the body does with it

Metabolism	Amantadine is primarily excreted unchanged in the urine via glomerular filtration and tubular secretion. It undergoes minimal hepatic metabolism, with less than 10% of the dose metabolized. Renal excretion accounts for approximately 90% of elimination.
Excretion	Renal excretion accounts for approximately 80% of elimination, with about 60% as unchanged drug and 20% as metabolites. Fecal excretion is minimal (<5%).
Half-life	The terminal elimination half-life is approximately 60–70 hours in healthy subjects, which supports once-daily dosing. Half-life may be prolonged in renal impairment.
Protein binding	Approximately 60–70% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd/F (apparent volume of distribution) is approximately 5–7 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral bioavailability is approximately 70–80% in healthy subjects; food does not significantly alter absorption.
Onset of Action	Oral: Onset of clinical effect (reduction in levodopa-induced dyskinesia) is typically observed within 2–4 weeks of initiating therapy.
Duration of Action	The duration of effect on dyskinesia is sustained over 24 hours with once-daily dosing, as reflected in clinical trials showing continuous benefit throughout the day.

Classification & Brands

Dosing & administration

Initial: 68.5 mg orally once daily at bedtime for 1 week; then increase to 137 mg once daily.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	eGFR 30–59 mL/min: 68.5 mg once daily; eGFR 15–29 mL/min: 68.5 mg every other day; eGFR <15 mL/min: not recommended.
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: 68.5 mg once daily; Child-Pugh Class C: not recommended.
Pediatric use	Not approved for patients <18 years; no established dosing.
Geriatric use	Initial dose 68.5 mg once daily with gradual titration; monitor for confusion, hallucinations, and falls.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for GOCOVRI (GOCOVRI).

Breastfeeding	No human data; M/P ratio unknown. Consider risk of galactorrhea and potential dopaminergic effects on infant. Decision: cautious use or avoid breastfeeding.
Teratogenic Risk	Insufficient human data; animal studies show no teratogenicity at clinically relevant doses. Risk cannot be excluded in first trimester. Second and third trimester: potential for premature labor or decreased fetal heart rate variability due to dopaminergic effects.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Patients with end-stage renal disease (eGFR < 15 mL/min/1.73 m²) or requiring hemodialysis.","Hypersensitivity to amantadine or any component of the formulation."]

Clinical Precautions

Precautions

["Suicidality and depression: Monitor for behavioral changes, depression, and suicidal ideation.","Falls and fractures: Increased risk due to dizziness, orthostatic hypotension, and gait disturbances.","Hallucinations and psychosis: May cause or exacerbate psychotic symptoms, especially in elderly patients.","Dizziness and orthostatic hypotension: Common, especially upon standing; monitor blood pressure.","Impulse control disorders: Pathological gambling, increased libido, hypersexuality, and compulsive behaviors have been reported.","Renal impairment: Dose adjustment required; contraindicated in patients with CrCl < 30 mL/min.","Abrupt discontinuation: May precipitate neuroleptic malignant syndrome (NMS) or withdrawal symptoms; taper gradually.","Ophthalmologic effects: Blurred vision; caution in patients with narrow-angle glaucoma."]

Clinical Tips & Counseling

Drug interactions

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GOCOVRI

Clinical safety rating: caution

Comprehensive clinical and safety monograph for GOCOVRI (GOCOVRI).

How it works

What the body does with it

Metabolism	Amantadine is primarily excreted unchanged in the urine via glomerular filtration and tubular secretion. It undergoes minimal hepatic metabolism, with less than 10% of the dose metabolized. Renal excretion accounts for approximately 90% of elimination.
Excretion	Renal excretion accounts for approximately 80% of elimination, with about 60% as unchanged drug and 20% as metabolites. Fecal excretion is minimal (<5%).
Half-life	The terminal elimination half-life is approximately 60–70 hours in healthy subjects, which supports once-daily dosing. Half-life may be prolonged in renal impairment.
Protein binding	Approximately 60–70% bound to plasma proteins, primarily albumin.
Volume of Distribution	Vd/F (apparent volume of distribution) is approximately 5–7 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral bioavailability is approximately 70–80% in healthy subjects; food does not significantly alter absorption.
Onset of Action	Oral: Onset of clinical effect (reduction in levodopa-induced dyskinesia) is typically observed within 2–4 weeks of initiating therapy.
Duration of Action	The duration of effect on dyskinesia is sustained over 24 hours with once-daily dosing, as reflected in clinical trials showing continuous benefit throughout the day.

Classification & Brands

Dosing & administration

Initial: 68.5 mg orally once daily at bedtime for 1 week; then increase to 137 mg once daily.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	eGFR 30–59 mL/min: 68.5 mg once daily; eGFR 15–29 mL/min: 68.5 mg every other day; eGFR <15 mL/min: not recommended.
Liver impairment	Child-Pugh Class A: no adjustment; Child-Pugh Class B: 68.5 mg once daily; Child-Pugh Class C: not recommended.
Pediatric use	Not approved for patients <18 years; no established dosing.
Geriatric use	Initial dose 68.5 mg once daily with gradual titration; monitor for confusion, hallucinations, and falls.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for GOCOVRI (GOCOVRI).

Breastfeeding	No human data; M/P ratio unknown. Consider risk of galactorrhea and potential dopaminergic effects on infant. Decision: cautious use or avoid breastfeeding.
Teratogenic Risk	Insufficient human data; animal studies show no teratogenicity at clinically relevant doses. Risk cannot be excluded in first trimester. Second and third trimester: potential for premature labor or decreased fetal heart rate variability due to dopaminergic effects.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Patients with end-stage renal disease (eGFR < 15 mL/min/1.73 m²) or requiring hemodialysis.","Hypersensitivity to amantadine or any component of the formulation."]