Amantadine

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Amantadine
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Adeel Jamil, M.D. [2]

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Overview

Amantadine is a adamantane, anticholinergic and antiparkinsonian agent that is FDA approved for the treatment of Influenza A, Influenza A prophylaxis, Parkinson's syndrome, drug-Induced extrapyramidal reactions. Common adverse reactions include orthostatic hypotension, peripheral edema, constipation, diarrhea, loss of appetite, nausea, xerostomia, ataxia, confusion, dizziness, headache, insomnia, somnolence, agitation, anxiety, depression. dream disorder, feeling nervous, hallucinations, irritability and fatigue..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Influenza A prophylaxis
Influenza A Treatment
Parkinson’s disease/Syndrome
Drug-Induced Extrapyramidal Reactions
Dosing Information
Dosage for prophylaxis and Treatment of Uncomplicated influenza A virus Illness
  • The adult daily dosage of amantadine hydrochloride capsules is 200 mg; two 100 mg capsules as a single daily dose. The daily dosage may be split into one capsule of 100 mg twice a day. If central nervous system effects develop in once-a-day dosage, a split dosage schedule may reduce such complaints. In persons 65 years of age or older, the daily dosage of amantadine hydrochloride capsules is 100 mg.
  • A 100 mg daily dose has also been shown in experimental challenge studies to be effective as prophylaxis in healthy adults who are not at high risk for influenza-related complications. However, it has not been demonstrated that a 100 mg daily dose is as effective as a 200 mg daily dose for prophylaxis, nor has the 100 mg daily dose been studied in the treatment of acute influenza illness. In recent clinical trials, the incidence of central nervous system (CNS) side effects associated with the 100 mg daily dose was at or near the level of placebo. The 100 mg dose is recommended for persons who have demonstrated intolerance to 200 mg of amantadine hydrochloride daily because of CNS or other toxicities.
Dosage for Parkinsonism
  • The usual dose of amantadine hydrochloride capsules is 100 mg twice a day when used alone. Amantadine has an onset of action usually within 48 hours.
  • The initial dose of amantadine hydrochloride capsules is 100 mg daily for patients with serious associated medical illnesses or who are receiving high doses of other antiparkinson drugs. After one to several weeks at 100 mg once daily, the dose may be increased to 100 mg twice daily, if necessary.
  • Occasionally, patients whose responses are not optimal with amantadine hydrochloride capsules at 200 mg daily may benefit from an increase up to 400 mg daily in divided doses. However, such patients should be supervised closely by their physicians.
  • Patients initially deriving benefit from amantadine hydrochloride capsules not uncommonly experience a fall-off of effectiveness after a few months. Benefit may be regained by increasing the dose to 300 mg daily. Alternatively, temporary discontinuation of amantadine hydrochloride capsules for several weeks, followed by reinitiation of the drug, may result in regaining benefit in some patients. A decision to use other antiparkinson drugs may be necessary.
Dosage for Concomitant Therapy
  • Some patients who do not respond to anticholinergic antiparkinson drugs may respond to amantadine hydrochloride capsules. When amantadine hydrochloride capsules or anticholinergic antiparkinson drugs are each used with marginal benefit, concomitant use may produce additional benefit.
  • When amantadine and levodopa are initiated concurrently, the patient can exhibit rapid therapeutic benefits. Amantadine hydrochloride capsules should be held constant at 100 mg daily or twice daily while the daily dose of levodopa is gradually increased to optimal benefit.
  • When amantadine is added to optimal well-tolerated doses of levodopa, additional benefit may result, including smoothing out the fluctuations in improvement which sometimes occur in patients on levodopa alone. Patients who require a reduction in their usual dose of levodopa because of development of side effects may possibly regain lost benefit with the addition of amantadine hydrochloride capsules.
Dosage for Drug Induced Extrapyramidal Reactions
  • The usual dose of amantadine hydrochloride capsules is 100 mg twice a day. Occasionally, patients whose responses are not optimal with amantadine hydrochloride capsules at 200 mg daily may benefit from an increase up to 300 mg daily in divided doses.
Dosage for Impaired Renal Function
This image is provided by the National Library of Medicine.
  • The recommended dosage for patients on hemodialysis is 200 mg every 7 days.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Amantadine hydrochloride in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Dosing Information
1 yr. to 9 yrs. of age
  • The total daily dose should be calculated on the basis of 2 to 4 mg/lb/day (4.4 to 8.8 mg/kg/day), but not to exceed 150 mg per day.
9 yrs. to 12 yrs. of age
  • The total daily dose is 200 mg given as one capsule of 100 mg twice a day. The 100 mg daily dose has not been studied in this pediatric population. Therefore, there are no data which demonstrate that this dose is as effective as or is safer than the 200 mg daily dose in this patient population.
  • Amantadine hydrochloride capsules should be continued daily for at least 10 days following a known exposure. If amantadine is used chemoprophylactically in conjunction with inactivated influenza A virus vaccine until protective antibody responses develop, then it should be administered for 2 to 4 weeks after the vaccine has been given. When inactivated influenza A virus vaccine is unavailable or contraindicated, amantadine hydrochloride capsules should be administered for the duration of known influenza A in the community because of repeated and unknown exposure.
  • Treatment of influenza A virus illness should be started as soon as possible, preferably within 24 to 48 hours after onset of signs and symptoms, and should be continued for 24 to 48 hours after the disappearance of signs and symptoms.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Amantadine hydrochloride in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Amantadine hydrochloride in pediatric patients.

Contraindications

  • Amantadine hydrochloride capsules, USP are contraindicated in patients with known hypersensitivity to amantadine hydrochloride or to any of the other ingredients in Amantadine hydrochloride capsules, USP.

Warnings

Deaths=

Suicide Attempts
CNS Effects
Other
PRECAUTIONS
Neuroleptic Malignant Syndrome (NMS)

Adverse Reactions

Clinical Trials Experience

  • The adverse reactions reported most frequently at the recommended dose of amantadine (5 to 10%) are: nausea, dizziness (lightheadedness), and insomnia.
  • Other adverse reactions reported during postmarketing experience with amantadine usage include:
Nervous System/Psychiatric
Cardiovascular
Respiratory
Gastrointestinal
Hematologic
Special Senses
Skin and Appendages
Miscellaneous
Laboratory Test

Postmarketing Experience

There is limited information regarding Clinical Trial Experience of Amantadine hydrochloride in the drug label.

Drug Interactions

  • Coadministration of thioridazine has been reported to worsen the tremor in elderly patients with Parkinson’s disease, however, it is not known if other phenothiazines produce a similar response. Coadministration of triamterene and hydrochlorothiazide capsules resulted in a higher plasma amantadine concentration in a 61-year-old man receiving amantadine (hydrochloride capsules) 100 mg t.i.d. for Parkinson’s disease.1 It is not known which of the components of triamterene and hydrochlorothiazide capsules contributed to the observation or if related drugs produce a similar response.
  • Coadministration of quinine or quinidine with amantadine was shown to reduce the renal clearance of amantadine by about 30%.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • The effect of amantadine on embryofetal and peri-postnatal development has not been adequately tested, that is, in studies conducted under Good Laboratory Practice (GLP) and according to current recommended methodology. However, in two non-GLP studies in rats in which females were dosed from 5 days prior to mating to Day 6 of gestation or on Days 7 to 14 of gestation, amantadine produced increases in embryonic death at an oral dose of 100 mg/kg (or 3 times the maximum recommended human dose on a mg/m2 basis). In the non-GLP rat study in which females were dosed on Days 7 to 14 of gestation, there was a marked increase in severe visceral and skeletal malformations at oral doses of 50 and 100 mg/kg (or 1.5 and 3 times, respectively, the maximum recommended human dose on a mg/m2 basis). The no-effect dose for teratogenicity was 37 mg/kg (equal to the maximum recommended human dose on a mg/m2 basis). The safety margins reported may not accurately reflect the risk considering the questionable quality of the study on which they are based. There are no adequate and well-controlled studies in pregnant women. Human data regarding teratogenicity after maternal use of amantadine is scarce. Tetralogy of Fallot and tibial hemimelia (normal karyotype) occurred in an infant exposed to amantadine during the first trimester of pregnancy (100 mg P.O. for 7 days during the 6th and 7th week of gestation). Cardiovascular maldevelopment (single ventricle with pulmonary atresia) was associated with maternal exposure to amantadine (100 mg/d) administered during the first 2 weeks of pregnancy.
  • Amantadine should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus.


Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Amantadine hydrochloride in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Amantadine hydrochloride during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Amantadine hydrochloride with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Amantadine hydrochloride with respect to pediatric patients.

Geriatic Use

Gender

There is no FDA guidance on the use of Amantadine hydrochloride with respect to specific gender populations.

Race

There is no FDA guidance on the use of Amantadine hydrochloride with respect to specific racial populations.

Renal Impairment

  • Because amantadine is mainly excreted in the urine, it accumulates in the plasma and in the body when renal function declines. Thus, the dose of amantadine should be reduced in patients with renal impairment and in individuals who are 65 years of age or older.

Hepatic Impairment

  • Care should be exercised when administering amantadine to patients with liver disease. Rare instances of reversible elevation of liver enzymes have been reported in patients receiving amantadine, though a specific relationship between the drug and such changes has not been established.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Amantadine hydrochloride in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Amantadine hydrochloride in patients who are immunocompromised.

Others

Melanoma
  • For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using amantadine for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).

Administration and Monitoring

Administration

  • Oral

Monitoring

Neuroleptic Malignant Syndrome (NMS)=

  • Sporadic cases of possible Neuroleptic Malignant Syndrome (NMS) have been reported in association with dose reduction or withdrawal of amantadine therapy. Therefore, patients should be observed carefully when the dosage of amantadine is reduced abruptly or discontinued, especially if the patient is receiving neuroleptics.
  • The management of NMS should include: 1) intensive symptomatic treatment and medical monitoring, and 2) treatment of any concomitant serious medical problems for which specific treatments are available. Dopamine agonists, such as bromocriptine, and muscle relaxants, such as dantrolene are often used in the treatment of NMS, however, their effectiveness has not been demonstrated in controlled studies.
Melanoma
  • For the reasons stated above, patients and providers are advised to monitor for melanomas frequently and on a regular basis when using amantadine for any indication. Ideally, periodic skin examinations should be performed by appropriately qualified individuals (e.g., dermatologists).

IV Compatibility

There is limited information regarding IV Compatibility of Amantadine hydrochloride in the drug label.

Overdosage

  • Deaths have been reported from overdose with amantadine. The lowest reported acute lethal dose was 1 gram. Because some patients have attempted suicide by overdosing with amantadine, prescriptions should be written for the smallest quantity consistent with good patient management.

Pharmacology

Template:Px
Template:Px
Amantadine
Systematic (IUPAC) name
adamantan-1-amine
Identifiers
CAS number 768-94-5
ATC code N04BB01
PubChem 2130
DrugBank DB00915
Chemical data
Formula Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox 
Mol. mass 151.249 g/mol
SMILES eMolecules & PubChem
Synonyms 1-Adamantylamine
Pharmacokinetic data
Bioavailability 86-90%[1]
Protein binding 67%[1]
Metabolism Minimal (mostly to acetyl metabolites)[1]
Half life 10-31 hours[1]
Excretion Urine[1]
Therapeutic considerations
Pregnancy cat.

B3(AU) C(US)

Legal status

Prescription Only (S4)(AU) ?(CA) POM(UK) [[Prescription drug|Template:Unicode-only]](US)

Routes oral

Mechanism of Action

Antiviral
  • The mechanism by which amantadine exerts its antiviral activity is not clearly understood. It appears to mainly prevent the release of infectious viral nucleic acid into the host cell by interfering with the function of the transmembrane domain of the viral M2 protein. In certain cases, amantadine is also known to prevent virus assembly during virus replication. It does not appear to interfere with the immunogenicity of inactivated influenza A virus vaccine.
Parkinson’s disease

Structure

  • Amantadine hydrochloride is designated chemically as 1-adamantanamine hydrochloride. Its molecular weight is 187.71 with a molecular formula C10H18NCl. It has the following structural formula:
This image is provided by the National Library of Medicine.

Pharmacodynamics

Antiviral Activity=

  • Amantadine inhibits the replication of influenza A virus isolates from each of the subtypes, i.e., H1N1, H2N2 and H3N2. It has very little or no activity against influenza B virus isolates. A quantitative relationship between the in vitro susceptibility of influenza A virus to amantadine and the clinical response to therapy has not been established in man. Sensitivity test results, expressed as the concentration of amantadine required to inhibit by 50% the growth of virus (ED50) in tissue culture vary greatly (from 0.1 mcg/mL to 25.0 mcg/mL) depending upon the assay protocol used, size of virus inoculum, isolates of influenza A virus strains tested, and the cell type used. Host cells in tissue culture readily tolerated amantadine up to a concentration of 100 mcg/mL.
Drug Resistance
  • Influenza A variants with reduced in vitro sensitivity to amantadine have been isolated from epidemic strains in areas where adamantane derivatives are being used. Influenza viruses with reduced in vitro sensitivity have been shown to be transmissible and to cause typical influenza illness. The quantitative relationship between the in vitro sensitivity of Influenza A variants to amantadine and the clinical response to therapy has not been established.

Pharmacokinetics

  • Amantadine is well absorbed orally. Maximum plasma concentrations are directly related to dose for doses up to 200 mg/day. Doses above 200 mg/day may result in a greater than proportional increase in maximum plasma concentrations. It is primarily excreted unchanged in the urine by glomerular filtration and tubular secretion. Eight metabolites of amantadine have been identified in human urine. One metabolite, an N-acetylated compound, was quantified in human urine and accounted for 5 to 15% of the administered dose. Plasma acetylamantadine accounted for up to 80% of the concurrent amantadine plasma concentration in 5 of 12 healthy volunteers following the ingestion of a 200 mg dose of amantadine. Acetylamantadine was not detected in the plasma of the remaining seven volunteers. The contribution of this metabolite to efficacy or toxicity is not known.
  • There appears to be a relationship between plasma amantadine concentrations and toxicity. As concentration increases, toxicity seems to be more prevalent, however, absolute values of amantadine concentrations associated with adverse effects have not been fully defined.
  • Amantadine pharmacokinetics were determined in 24 normal adult male volunteers after the oral administration of a single amantadine hydrochloride 100 mg soft gel capsule. The mean ± SD maximum plasma concentration was 0.22 ± 0.03 mcg/mL (range: 0.18 to 0.32 mcg/mL). The time to peak concentration was 3.3 ± 1.5 hours (range 1.5 to 8.0 hours). The apparent oral clearance was 0.28 ± 0.11 L/hr/kg (range: 0.14 to 0.62 L/hr/kg). The half-life was 17 ± 4 hours (range: 10 to 25 hours). Across other studies, amantadine plasma half-life has averaged 16 ± 6 hours (range: 9 to 31 hours) in 19 healthy volunteers.
  • After oral administration of a single dose of 100 mg amantadine syrup to five healthy volunteers, the mean ± SD maximum plasma concentration Cmax was 0.24 ± 0.04 mcg/mL and ranged from 0.18 to 0.28 mcg/mL. After 15 days of amantadine 100 mg b.i.d., the Cmax was 0.47 ± 0.11 mcg/mL in four of the five volunteers. The administration of amantadine tablets as a 200 mg single dose to 6 healthy subjects resulted in a Cmax of 0.51 ± 0.14 mcg/mL. Across studies, the time to Cmax (Tmax) averaged about 2 to 4 hours.
  • Plasma amantadine clearance ranged from 0.2 to 0.3 L/hr/kg after the administration of 5 mg to 25 mg intravenous doses of amantadine to 15 healthy volunteers.
  • In six healthy volunteers, the ratio of amantadine renal clearance to apparent oral plasma clearance was 0.79 ± 0.17 (mean ± SD).
  • The volume of distribution determined after the intravenous administration of amantadine to 15 healthy subjects was 3 to 8 L/kg, suggesting tissue binding. Amantadine, after single oral 200 mg doses to 6 healthy young subjects and to 6 healthy elderly subjects has been found in nasal mucus at mean ± SD concentrations of 0.15 ± 0.16, 0.28 ± 0.26, and 0.39 ± 0.34 mcg/g at 1, 4 and 8 hours after dosing, respectively. These concentrations represented 31 ± 33%, 59 ± 61% and 95 ± 86% of the corresponding plasma amantadine concentrations. Amantadine is approximately 67% bound to plasma proteins over a concentration range of 0.1 to 2.0 mcg/mL. Following the administration of amantadine 100 mg as a single dose, the mean ± SD red blood cell to plasma ratio ranged from 2.7 ± 0.5 in 6 healthy subjects to 1.4 ± 0.2 in 8 patients with renal insufficiency.
  • The apparent oral plasma clearance of amantadine is reduced and the plasma half-life and plasma concentrations are increased in healthy elderly individuals age 60 and older. After single dose administration of 25 to 75 mg to 7 healthy, elderly male volunteers, the apparent plasma clearance of amantadine was 0.10 ± 0.04 L/hr/kg (range 0.06 to 0.17 L/hr/kg) and the half-life was 29 ± 7 hours (range 20 to 41 hours). Whether these changes are due to decline in renal function or other age related factors is not known.
  • In a study of young healthy subjects (n=20), mean renal clearance of amantadine, normalized for body mass index, was 1.5 fold higher in males compared to females (p<0.032).
  • Compared with otherwise healthy adult individuals, the clearance of amantadine is significantly reduced in adult patients with renal insufficiency. The elimination half-life increases two to three fold or greater when creatinine clearance is less than 40 mL/min/1.73 m2 and averages eight days in patients on chronic maintenance hemodialysis. Amantadine is removed in negligible amounts by hemodialysis.
  • The pH of the urine has been reported to influence the excretion rate of amantadine. Since the excretion rate of amantadine increases rapidly when the urine is acidic, the administration of urine acidifying drugs may increase the elimination of the drug from the body.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Amantadine hydrochloride in the drug label.

Clinical Studies

Carcinogenesis and Mutagenesis
  • Long-term in vivo animal studies designed to evaluate the carcinogenic potential of amantadine have not been performed. In several in vitro assays for gene mutation, amantadine did not increase the number of spontaneously observed mutations in four strains of Salmonella typhimurium (Ames Test) or in a mammalian cell line (Chinese Hamster Ovary cells) when incubations were performed either with or without a liver metabolic activation extract.
  • Further, there was no evidence of chromosome damage observed in an in vitro test using freshly derived and stimulated human peripheral blood lymphocytes (with and without metabolic activation) or in an in vivo mouse bone marrow micronucleus test (140 to 550 mg/kg; estimated human equivalent doses of 11.7 to 45.8 mg/kg based on body surface area conversion).
Impairment of Fertility
  • The effect of amantadine on fertility has not been adequately tested, that is, in a study conducted under Good Laboratory Practice (GLP) and according to current recommended methodology. In a three litter, non-GLP, reproduction study in rats, amantadine at a dose of 32 mg/kg/day (equal to the maximum recommended human dose on a mg/m2 basis) administered to both males and females slightly impaired fertility. There were no effects on fertility at a dose level of 10 mg/kg/day (or 0.3 times the maximum recommended human dose on a mg/m2 basis); intermediate doses were not tested.

How Supplied

  • Amantadine hydrochloride capsules, USP for oral administration are available as:
  • 100 mg: Red capsules imprinted GG 634 and supplied as:
    • NDC 51079-247-20 - Unit dose blister packages of 100 (10 cards of 10 capsules each).

Storage

  • Store at 20° to 25°C (68° to 77°F).

Images

Drug Images

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Package and Label Display Panel

NDC 51079-247-20

AMANTADINE HYDROCHLORIDE CAPSULES, USP 100 mg

100 Capsules (10 x 10)

Each capsule contains: Amantadine Hydrochloride, USP 100 mg

Usual Dosage: See accompanying prescribing information.

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature].

Manufactured by: Sandoz Inc. Princeton, NJ 08540

Rx only

S-11371

Packaged and Distributed by:

UDL LABORATORIES, INC.

ROCKFORD, IL 61103

This unit dose package is not child resistant.

For institutional use only.

Keep this and all drugs out of the reach of children.

This container provides light-resistance.

See window for lot number and expiration date. {{#ask: Label Page::Amantadine |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}

Patient Counseling Information

Patients should be advised of the following information:

  • Blurry vision and/or impaired mental acuity may occur.
  • Gradually increase physical activity as the symptoms of Parkinson’s disease improve.
  • Avoid excessive alcohol usage, since it may increase the potential for CNS effects such as dizziness, confusion, light-headedness and orthostatic hypotension.
  • Avoid getting up suddenly from a sitting or lying position. If dizziness or lightheadedness occurs, notify physician.
  • Notify physician if mood/mental changes, swelling of extremities, difficulty urinating and/or shortness of breath occur.
  • Do not take more medication than prescribed because of the risk of overdose. If there is no improvement in a few days, or if medication appears less effective after a few weeks, discuss with a physician.
  • Consult physician before discontinuing medication.
  • Seek medical attention immediately if it is suspected that an overdose of medication has been taken.
  • There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges, and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease, including amantadine. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges or other urges while being treated with amantadine. Patients should inform their physician if they experience new or increased gambling urges, increased sexual urges or other intense urges while taking amantadine. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking amantadine.

Precautions with Alcohol

Alcohol-Amantadine hydrochloride interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • Symmetrel®

Look-Alike Drug Names

  • amantadine® - amiodarone®

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "SYMMETREL® (amantadine hydrochloride)" (PDF). TGA eBusiness Services. NOVARTIS Pharmaceuticals Australia Pty Limited. 29 June 2011. Retrieved 24 February 2014.


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References

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