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2010 4:34PM

AMANTADINE
THERAPEUTICS symptoms, including autonomic symptoms
such as postural hypotension, depression,
Brands and bladder dysfunction, do not improve.
*
Symmetrel If the patient has significantly impaired
functioning, add levodopa or a dopamine
Generic? agonist
Yes *
Fatigue – MS-related fatigue may respond to
pemoline or modafinil
Class Best Augmenting Combos
*
Antiparkinson agent for Partial Response or
Commonly Prescribed for Treatment-Resistance
(FDA approved in bold)
*
For suboptimal effectiveness add carbidopa-
*
Parkinson’s disease (PD) levodopa with or without a COMT inhibitor or
*
Drug-induced extrapyramidal reactions dopamine agonist depending on disease
*
Influenza-A prophylaxis/treatment severity. Monoamine oxidase (MAO)-B
*
Post-encephalitic Parkinsonism inhibitors may also be beneficial
*
Vascular Parkinsonism
*
For younger pat0ients with bothersome
*
Fatigue in multiple sclerosis (MS) tremor: anticholinergics may help
*
Enhancing arousal after traumatic brain
*
For severe motor fluctuations and/or
injury dyskinesias with good “on” time, functional
*
Attention deficit hyperactivity disorder neurosurgery is an option
*
SSRI-related sexual dysfunction
*
Depression is common in PD and may
respond to low dose selective serotonin
reuptake inhibitors
*
Cognitive impairment/dementia is common
How the Drug Works in mid-late stage PD and may improve with
*
The mechanism of action in PD is poorly acetylcholinesterase inhibitors
understood but animal studies suggest *
For patients with late-stage PD
either that it induces release or decreases experiencing hallucinations or delusions,
reuptake of dopamine. Also is a weak withdraw amantadine and consider oral
N-methyl-D-aspartic acid (NMDA) receptor atypical neuroleptics (quetiapine,
antagonist which in animals decreases olanzapine, clozapine). Acute psychosis is
release of acetylcholine from the striatum. a medical emergency that may require
Treats and prevents influenza-A by hospitalization
preventing the release of viral nucleic
acid into the host cell due to interfering Tests
with the function of a viral M2 protein. It *
None required
may also prevent virus assembly during
replication

How Long Until It Works ADVERSE EFFECTS (AEs)

*
PD – 48 hours or less
How Drug Causes AEs
If It Works *
Effects on dopamine concentrations and
*
PD – most patients require dose adjustment possible anticholinergic effects
over time and most PD patients will need to
take other agents, such as levodopa Notable AEs
*
Nausea, dizziness, insomnia, and blurry
If It Doesn’t Work vision most common. Depression, anxiety,
*
PD – Motor symptoms, such as confusion, livedo reticularis, dry mouth,
bradykinesia, gait, and tremor should constipation, peripheral edema, orthostatic
improve. Reduces extrapyramidal reactions, hypotension, nervousness, and headache
such as dyskinesias, and can allow reduction can occur. Can exacerbate preexisting
of carbidopa-levodopa doses. Non-motor seizure disorders

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AMANTADINE (continued)

Overdose
Life-Threatening or *
Symptoms relate to anticholinergic effects.
Dangerous AEs May include renal, respiratory, or CNS AEs
*
Abrupt discontinuation has been associated or cardiac effects, including arrhythmia,
with the development of neuroleptic tachycardia, or hypertension. Deaths have
malignant syndrome been reported with as little as 1 g
*
Rare suicide attempts or ideation, even in
those with no history of psychiatric Long-Term Use
disorders *
Safe for long-term use. Effectiveness may
decrease over time
Weight Gain
*
Unusual Habit Forming
*
No
unusual not unusual common problematic

Sedation How to Stop

*
Taper slowly and monitor for parkinsonian
*
Not unusual
crisis. Abrupt withdrawal may also
precipitate delirium, hallucinations, agitation,
unusual not unusual common problematic depression, pressured speech, anxiety,
stupor, or paranoia
What to Do About AEs
*
Titrate slowly to avoid GI side effects. Most
AEs require reducing dose or stopping
Pharmacokinetics
medication
*
Most of the drug is excreted unchanged in
the urine. Peak effect is at 1.5–8 hours and
Best Augmenting Agents for AEs half-life an average of 17 hours. Doses
*
Most AEs cannot be improved by use of an over 200 mg may cause greater than
augmenting agent proportional increases in levels

DOSING AND USE Drug Interactions

*
Anticholinergics can increase the
Usual Dosage Range mild anticholinergic effects of
*
PD – 100–200 mg in divided doses. amantadine
Occasionally up to 400 mg/day *
Quinidine, triamterene, thiazide diuretics,
and trimethoprim/sulfamethoxazole impair
Dosage Forms renal clearance of amantadine and can
*
Tablets/Capsules: 100 mg increase plasma concentrations
*
`Syrup: 50 mg/5ml *
Thioridazine with amantadine can increase
PD tremor
How to Dose
*
Start at 100 mg daily or 100 mg twice daily in
patients on no other PD medications with no
other major medical problems. In 1 week or Other Warning Precautions
more can increase by 100 mg *
May cause mydriasis due to anticholinergic
*
Occasional patients will require doses of AEs. Do not give to patients with
300 mg or 400 mg in divided doses to untreated angle closure glaucoma
achieve optimal clinical effect
Do Not Use
*
Known hypersensitivity to the drug
Dosing Tips
*
Initial sedation may improve with time or
dividing doses

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(continued) AMANTADINE

SPECIAL POPULATIONS THE ART OF NEUROPHARMACOLOGY

Renal Impairment Potential Advantages
*
Decrease dose for impaired function. *
Relief of dyskinesias in PD. Relatively
Creatinine clearance 30–50 mL/min: 200 day quick-acting and less sedation than other
1 then 100 daily. 15–29: 200 day 1 then treatments
100 every other day. <15 or hemodialysis:
200 mg every 7 days Potential Disadvantages
Hepatic Impairment
*
Usually not first-line treatment. No
evidence of neuroprotection against PD.
*
May cause elevation of liver enzymes. Use
Generally less effective than levodopa and
with caution
risks significant CNS AEs including
Cardiac Impairment hallucinations
*
Infrequently causes congestive heart failure
or peripheral edema. Use with caution Primary Target Symptoms
*
PD – motor dysfunction and
Elderly dyskinesias
*
There is reduced drug clearance, but no dose
adjustment needed as the dose used is the
lowest that provides clinical improvement
Pearls
*
Useful for PD patients with dyskinesias
Children and Adolescents *
Can cause anticholinergic AEs (dry mouth,
*
Use for influenza treatment in children aged 1 urinary retention) despite no known action
or greater. (PD is rare in pediatrics.) on receptors. This and hallucinations may
limit treatment
*
Used for the treatment of MS-related fatigue
at doses of 200–400 mg/day
Pregnancy *
May be useful in the treatment of traumatic
*
Category C. Teratogenic in some animal brain injury, including children, at doses of
studies. Risks may include cardiovascular 200–400 mg/daily
maldevelopment. Use only if benefits of
medication outweigh risks

Breast Feeding
*
Excreted in breast milk. Do not use

Suggested Reading
Abdel-Salam OM. Drugs used to treat Pucci E, Branãs P, D’Amico R, Giuliani G, Solari A,
Parkinson’s disease, present status and future Taus C. Amantadine for fatigue in multiple sclerosis.
directions. CNS Neurol Disord Drug Targets Cochrane Database Syst Rev 2007;(1):CD002818.
2008;7(4):321–42.
Sawyer E, Mauro LS, Ohlinger MJ. Amantadine
Chen JJ, Swope DM. Pharmacotherapy for enhancement of arousal and cognition after
Parkinson’s disease. Pharmacotherapy traumatic brain injury. Ann Pharmacother
2007;27(12 Pt 2):161S–173S. 2008;42(2):247–52.

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