amantadine (Endantadine, Symmetrel)
Classes: Antivirals, Influenza; Antiparkinson Agents, Dopamine Agonists
Dosing and uses of Endantadine, Symmetrel (amantadine)
Adult dosage forms and strengths
capsule/tablet
- 100mg
syrup
- 50mg/5mL
Parkinson Disease
Serious illness or high dose of other antiparkinson agents: 100 mg/day PO initially; may be increased to 100 mg q12hr after at least 1 week
Up to 400 mg/day, but only in special circumstances
Drug-Induced Extrapyramidal Symptoms
100 mg PO q12hr; not to exceed 300 mg/day
Levodopa-induced Dyskinesia (Orphan)
Orphan designation for treatment of levodopa-induced dyskinesia
Sponsor
- Osmotica Pharmaceutical Corporation; Regulatory, Clinical Operations & Legal; Lumina Station #2, Suite 209-A; Wilmington, NC 28403
Dosage modifications
Renal impairment
- CrCl 30-50 mL/min: 200 mg PO on 1st day, then 100 mg/day PO
- CrCl 15-29 mL/min: 200 mg PO on 1st day, then 100 mg PO every other day
- CrCl <15 mL/min; hemodialysis: 200 mg PO weekly
Administration
Administer in 2 divided doses to decrease adverse CNS effects; administer 2nd dose several hours before bedtime to minimize insomnia
Pediatric dosage forms and strengths
capsule/tablet
- 100mg
syrup
- 50mg/5mL
Influenza A Treatment
NOTE: Because of resistance, amantadine is no longer recommended for prophylaxis or treatment of influenza A; refer to current ACIP recommendations
1-9 years or <40 kg (any age): 5 mg/kg/day PO in single dose or divided q12 hr; not to exceed 150 mg/day
≥10 years and <40 kg: 5 mg/kg/day PO divided q12hr
≥10 years and ≥40 kg: 100 mg PO q12hr
Geriatric dosage forms and strengths
Parkinson Disease
>65 years: Therapy should be based on renal function
Endantadine, Symmetrel (amantadine) adverse (side) effects
1-10%
Agitation
Anorexia
Anxiety
Ataxia
Confusion
Constipation
Depression
Diarrhea
Dizziness
Dream abnormality
Dry nose
Fatigue
Hallucinations
Headache
Insomnia
Irritability
Livedo reticularis
Nausea
Nervousness
Orthostatic hypotension
Peripheral edema
Somnolence
Xerostomia
<1%
Amnesia
CHF
Decreased libido
Dyspnea
Eczematoid dermatitis
Euphoria
Hyperkinesis
Hypertension
Instances of convulsions
Leukopenia
Neutropenia
Oculogyric episodes
Psychosis
Rash
Slurred speech
Urinary retention
Visual disturbances
Vomiting
Weakness
Warnings
Contraindications
Hypersensitivity to amantadine, rimantadine
Untreated narrow-angle glaucoma
Breastfeeding
Cautions
Since 2008-09 influenza season, Centers for Disease Control and Prevention (CDC) advises against use for treatment or prophylaxis of influenza in Us
CHF, peripheral edema, orthostatic hypotension
Renal impairment, liver disease
Advanced age
History of seizures, eczematoid rash, severe psychosis or psychoneurosis
Dosages >200 mg/day
Consider reducing anticholinergic dosages before initiating amantadine therapy
Avoid abrupt withdrawaL
Risk of neuroleptic malignant syndrome (NMS) with dosage reduction or withdrawaL
May impair ability to perform hazardous tasks
Possibility of reduced effectiveness after several months; may regain efficacy if dosage is increased
Parkinson patients
- Risk of uncontrollable sexual, gambling, or other urges
- May be linked to higher melanoma risk
Pregnancy and lactation
Pregnancy category: C
Lactation: Drug enters breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Endantadine, Symmetrel (amantadine)
Mechanism of action
Prevents release of infectious viral nucleic acid
May promote dopamine release from presynaptic fibers or block reuptake of dopamine into presynaptic neurons
Absorption
Bioavailability: 86-90%
Onset: Within 48 hr (antidyskinetic)
Peak plasma time: 2-4 hr
Peak plasma concentration (100-mg single dose): 0.24 mcg/mL
Distribution
Protein bound: 67%
Vd: 1.5-6.1 L/kg (normal renal function)
Metabolism
Not appreciably metabolized; small amounts of acetyl metabolite identified
Elimination
Half-life: 16 hr (average with normal renal function)
Total body clearance: 0.2-0.3 L/hr/kg
Excretion: Urine (80-90% unchanged) by glomerular filtration and tubular secretion
