SYMADINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SYMADINE (SYMADINE).

How it works

SYMADINE (amantadine) is a tricyclic amine that inhibits influenza A virus replication by blocking the viral M2 ion channel, which prevents uncoating of viral RNA. It also increases dopamine release and inhibits dopamine reuptake in the CNS, providing antiparkinsonian effects.

What the body does with it

Metabolism	Amantadine is primarily excreted unchanged in urine via glomerular filtration and tubular secretion. Minor metabolism via N-acetylation and hydroxylation has been reported, but specific enzymes are not well characterized.
Excretion	Renal elimination of unchanged drug accounts for approximately 90% of the administered dose. Biliary/fecal excretion is minimal (<5%).
Half-life	The terminal elimination half-life is approximately 24 hours in patients with normal renal function. In patients with renal impairment (CrCl <50 mL/min), the half-life is significantly prolonged, requiring dose adjustment. The long half-life allows for once-daily dosing.
Protein binding	Approximately 67% bound to plasma proteins, primarily albumin.
Volume of Distribution	The apparent volume of distribution is approximately 5–10 L/kg, indicating extensive tissue distribution and penetration into the CNS.
Bioavailability	Oral bioavailability is 90–100%, indicating nearly complete absorption. No significant first-pass metabolism.
Onset of Action	For oral administration, clinical effect typically begins within 48 hours. For intravenous administration (if applicable), onset is more rapid, within hours. In Parkinson's disease, improvement in symptoms may be observed within the first few days.
Duration of Action	Duration of clinical effect is approximately 24 hours, supporting once-daily dosing. Clinical benefits are maintained with consistent dosing. In antiviral use, duration covers the treatment course.

Classification & Brands

Dosing & administration

100 mg orally every 12 hours; immediate-release formulation.

Dosage form	CAPSULE
Renal impairment	CrCl 30-50 mL/min: 100 mg every 24 hours; CrCl 15-29 mL/min: 100 mg every 48 hours; CrCl <15 mL/min or hemodialysis: 200 mg every 7 days.
Liver impairment	No specific Child-Pugh based adjustments are established; use with caution in severe hepatic impairment.
Pediatric use	1-9 years: 4.4-8.8 mg/kg/day divided every 12 hours, max 150 mg/day; ≥10 years: same as adult.
Geriatric use	Reduce dose or extend interval due to age-related renal decline; consider starting at 100 mg daily.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SYMADINE (SYMADINE).

Breastfeeding	Unknown if excreted in human breast milk. M/P ratio not established. Caution advised due to potential for adverse effects in nursing infants, such as bradycardia or hypotension.
Teratogenic Risk	Pregnancy Category C. First trimester: Risk of teratogenicity cannot be ruled out; animal studies show fetal harm but human data insufficient. Second and third trimesters: Potential for neonatal hypotension, bradycardia, respiratory depression, and hypoglycemia with chronic use.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to amantadine or any component; end-stage renal disease (CrCl <15 mL/min) due to accumulation; concurrent use with live attenuated influenza vaccine (intranasal) due to risk of vaccine virus replication; caution in patients with epilepsy (may increase seizure frequency), congestive heart failure, or history of recurrent eczematoid dermatitis.

Clinical Precautions

Precautions

May cause CNS effects including dizziness, confusion, and hallucinations; caution in elderly and patients with renal impairment; neuroleptic malignant syndrome-like symptoms reported with abrupt discontinuation; suicidal ideation and depression; orthostatic hypotension; peripheral edema; rare episodes of acute angle-closure glaucoma in patients with untreated narrow-angle glaucoma.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

SYMADINE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for SYMADINE (SYMADINE).

How it works

What the body does with it

Metabolism	Amantadine is primarily excreted unchanged in urine via glomerular filtration and tubular secretion. Minor metabolism via N-acetylation and hydroxylation has been reported, but specific enzymes are not well characterized.
Excretion	Renal elimination of unchanged drug accounts for approximately 90% of the administered dose. Biliary/fecal excretion is minimal (<5%).
Half-life	The terminal elimination half-life is approximately 24 hours in patients with normal renal function. In patients with renal impairment (CrCl <50 mL/min), the half-life is significantly prolonged, requiring dose adjustment. The long half-life allows for once-daily dosing.
Protein binding	Approximately 67% bound to plasma proteins, primarily albumin.
Volume of Distribution	The apparent volume of distribution is approximately 5–10 L/kg, indicating extensive tissue distribution and penetration into the CNS.
Bioavailability	Oral bioavailability is 90–100%, indicating nearly complete absorption. No significant first-pass metabolism.
Onset of Action	For oral administration, clinical effect typically begins within 48 hours. For intravenous administration (if applicable), onset is more rapid, within hours. In Parkinson's disease, improvement in symptoms may be observed within the first few days.
Duration of Action	Duration of clinical effect is approximately 24 hours, supporting once-daily dosing. Clinical benefits are maintained with consistent dosing. In antiviral use, duration covers the treatment course.

Classification & Brands

Dosing & administration

100 mg orally every 12 hours; immediate-release formulation.

Dosage form	CAPSULE
Renal impairment	CrCl 30-50 mL/min: 100 mg every 24 hours; CrCl 15-29 mL/min: 100 mg every 48 hours; CrCl <15 mL/min or hemodialysis: 200 mg every 7 days.
Liver impairment	No specific Child-Pugh based adjustments are established; use with caution in severe hepatic impairment.
Pediatric use	1-9 years: 4.4-8.8 mg/kg/day divided every 12 hours, max 150 mg/day; ≥10 years: same as adult.
Geriatric use	Reduce dose or extend interval due to age-related renal decline; consider starting at 100 mg daily.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for SYMADINE (SYMADINE).

Breastfeeding	Unknown if excreted in human breast milk. M/P ratio not established. Caution advised due to potential for adverse effects in nursing infants, such as bradycardia or hypotension.
Teratogenic Risk	Pregnancy Category C. First trimester: Risk of teratogenicity cannot be ruled out; animal studies show fetal harm but human data insufficient. Second and third trimesters: Potential for neonatal hypotension, bradycardia, respiratory depression, and hypoglycemia with chronic use.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

None

Side Effect Profile

Serious Effects

Absolute Contraindications

Clinical Precautions

Precautions

Clinical Tips & Counseling

Drug interactions

Loading safety data…