DrugindexOnline^{2nd edition}

Pronouncation: (uh-MAN-tuh-deen HIGH-droe-KLOR-ide)
Class: Antiparkinson, Antiviral

Trade Names:
Symmetrel
- Tablets 100 mg
- Syrup 50 mg/5 mL

Trade Names:
Amantadine Hydrochloride
- Capsules 100 mg

Endantadine (Canada)
Gen-Amantadine (Canada)
Symmetrel (Canada)

Mechanism of Action

Pharmacology

Exact mechanism is unknown; thought to facilitate dopamine release from intact dopaminergic terminals, increasing dopamine concentration at dopaminergic terminals. Exhibits antiviral activity against influenza A virus by inhibiting entry of virus into host cell.

Pharmacokinetics

Absorption

Well absorbed. C _max is about 0.22 mcg/mL and T _max is about 3.3 h.

Distribution

Vd is 3 to 8 L/kg and about 67% protein bound.

Metabolism

8 metabolites were identified.

Elimination

Primarily excreted unchanged in the urine. Cl is about 0.28 L/h/kg. The t _½ is about 17 h. Excretion increases when urine is acidic.

Special Populations

Renal Function Impairment

Elimination t _½ increased 2- to 3-fold or greater when Ccr is less than 40 mL/min/1.73 m ² .

Elderly

Cl reduced and plasma t _½ and concentrations are increased.

Indications and Usage

Symptomatic treatment of several forms of Parkinson disease or syndrome and drug-induced extrapyramidal reactions; prevention and treatment of influenza A viral respiratory illness, especially in high-risk patients.

Contraindications

Standard considerations.

Dosage and Administration

Parkinson Disease
Adults

PO 100 mg twice daily when used as single agent.

Initial dose

PO 100 mg/day if patient is debilitated or receiving high doses of other antiparkinson drugs. If necessary, dose may be titrated to max of 400 mg/day.

Drug-Induced Extrapyramidal Reactions
Adults

PO 100 mg twice daily; up to 300 mg/day may be given in divided doses.

Influenza A Viral Infection (Symptomatic Treatment)
Adults

PO 200 mg/day as single dose or 100 mg twice daily. If CNS effects develop on a once-daily dosage, split dosage schedule may reduce complaints.

Elderly over 65 yr of age

PO 100 mg every day.

Children 9 to 12 yr of age

PO 100 mg twice daily.

Children 1 to 9 yr of age

PO 4.4 to 8.8 mg/kg/day; not to exceed 150 mg/day.

Renal Impairment
Adults

PO Ccr 30 to 50 mL/min: Administer 200 mg first day followed by 100 mg/day thereafter; Ccr 15 to 29 mL/min: Administer 200 mg first day followed by 100 mg on alternate days; Ccr less than 15 mL/min and hemodialysis patients: Administer 200 mg every 7 days.

Influenza A Viral Infection (Prophylaxis)

Same dosages as for symptomatic treatment. However, start in anticipation of contact or as soon as possible after exposure. Continue drug administration for at least 10 days after known exposure. When influenza A virus vaccine is unavailable or contraindicated, administer amantadine for up to 90 days. In conjunction with the vaccine, administer amantadine for 2 to 3 wk after vaccination.

Storage/Stability

Store tablets, capsules, and syrup at controlled room temperature (59° to 86°F).

Drug Interactions

Anticholinergic agents, quinidine, quinine, triamterene, thiazide diuretics, trimethoprim-sulfamethoxazole

May increase the effects of amantadine.

CNS stimulants

The effects of the CNS stimulant may be increased by amantadine.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Orthostatic hypotension (1% to 5%); cardiac arrest, arrhythmias (including malignant arrhythmias), hypotension, tachycardia (postmarketing).

CNS

Dizziness, lightheadedness, insomnia (5% to 10%); depression, anxiety, irritability, hallucinations, confusion, headache, somnolence, nervousness, abnormal dreams, agitation (1% to 5%); coma, stupor, delusions, aggressive behavior, paranoid reaction, manic reaction, involuntary muscle contractions, abnormal gait, paresthesia, EEG changes, tremor, (postmarketing).

Dermatologic

Pruritus, diaphoresis (postmarketing).

EENT

Dry nose (1% to 5%); keratitis, mydriasis (postmarketing).

GI

Nausea (5% to 10%); dry mouth, constipation, diarrhea (1% to 5%); dysphagia (postmarketing).

Hematologic

Leukocytosis (postmarketing).

Lab Tests

Elevated CPK, BUN, serum creatinine, alkaline phosphatase, LDH, bilirubin, glucose tolerance test, AST, ALT.

Respiratory

Acute respiratory failure, pulmonary edema, tachypnea (postmarketing).

Miscellaneous

Ataxia, livedo reticularis, peripheral edema, fatigue (1% to 5%); allergic reactions (including anaphylactic reactions, edema, and fever), neuroleptic malignant syndrome (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Safety and efficacy in newborns and infants under 1 yr not established.

Elderly

Decreased dosage is necessary.

Renal Function

Reduced dose is required in renal function impairment.

Hepatic Function

Use with caution.

Special Risk Patients

Use with caution in patients with a history of recurrent eczematoid rash, psychosis, or severe psychoneurosis not controlled by chemotherapeutic agents.

CHF

CHF has developed in patients taking amantadine.

Glaucoma

Because amantadine has anticholinergic effects and may cause mydriasis, do not give to patients with untreated angle-closure glaucoma.

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome may occur in association with dose reduction or withdrawal of amantadine therapy.

Seizures

Reduced dose is necessary in patients with prior seizure disorders, including epilepsy.

Suicide

Successful suicide and suicide attempts have been reported in patients with and without a history of psychiatric illness.

Overdosage

Symptoms

Death, cardiac, respiratory, renal, or CNS toxicity, cardiac dysfunction (including arrhythmia, tachycardia, and hypertension), pulmonary edema, respiratory distress (including adult respiratory distress syndrome), renal dysfunction (including increased BUN, decreased Ccr and renal insufficiency), CNS effects (including insomnia, anxiety, agitation, aggressive behavior, hypertonia, hyperkinesias, ataxia, gait abnormality, tremor, confusion, disorientation, depersonalization, fear, delirium, hallucinations, psychotic reactions, lethargy, somnolence, and coma), seizures, hyperthermia.

Patient Information

• Advise patient to take dose every day or twice daily as prescribed and not to stop taking or change the dose unless advised by health care provider.
• Advise patient to take without regard to meals but to take with food if GI upset occurs.
• Caution patient taking amantadine for Parkinson disease that rapid discontinuation of the medication can worsen Parkinson symptoms and cause other severe neurological changes (eg, agitation, delusions, hallucinations). Advise patient that if medication needs to be discontinued, it should be done by slowly reducing the dose.
• Caution patient to avoid alcohol and other CNS depressants (eg, sedatives) while using this medication.
• Caution patient that drug may cause blurred vision and impaired mental alertness and to use caution driving or performing other tasks requiring mental alertness until tolerance is determined.
• Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Advise patient to arise slowly from a lying or sitting position to reduce the chances of dizziness occurring.
• Advise patient to report any of the following to health care provider: mood changes or changes in thinking or behavior, dizziness or lightheadedness when arising from a sitting or lying position, swelling of the arms or legs, difficulty urinating, shortness of breath.