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Amantadine

Brand name: Gocovri Osmolex ER
Drug class: Adamantanes
VA class: AM800
CAS number: 665-66-7

Medically reviewed by Drugs.com on Feb 14, 2022. Written by ASHP.

Introduction

Antiviral; antiparkinsonian agent; adamantane derivative.

Uses for Amantadine

Treatment of Seasonal Influenza A Virus Infections

Has been used for treatment of uncomplicated respiratory tract illness caused by susceptible influenza A virus in adults, adolescents, and children ≥1 year of age.

Amantadine and rimantadine have little or no activity against influenza B; not used for treatment of influenza B infection.

Beginning in the 2005–2006 influenza season, most strains of influenza A (H3N2) circulating in the US were resistant to adamantanes (amantadine, rimantadine), and resistance to these drugs among seasonal influenza A (H3N2) isolates has remained high during subsequent influenza seasons. In addition, the influenza A (H1N1)pdm09 virus circulating during recent influenza seasons is resistant to amantadine and rimantadine.

CDC and other experts recommend that adamantanes (amantadine, rimantadine) not be used for treatment of seasonal influenza in the US until susceptibility to these antiviral agents has been reestablished in circulating influenza A viruses.

Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for treatment of seasonal influenza. Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve.

CDC issues recommendations concerning use of antivirals for treatment of influenza, and these recommendations are updated as needed during each influenza season. Information regarding influenza surveillance and updated recommendations for treatment of seasonal influenza are available from CDC at [Web].

Prevention of Seasonal Influenza A Virus Infections

Has been used for prophylaxis of signs and symptoms of influenza infection caused by susceptible influenza A in adults, adolescents, and children ≥1 year of age.

Amantadine and rimantadine have little or no activity against influenza B; not used for prevention of influenza B infection.

Annual vaccination with seasonal influenza virus vaccine, as recommended by the US Public Health Service Advisory Committee on Immunization Practices (ACIP), is the primary means of preventing seasonal influenza and its severe complications. Prophylaxis with an appropriate antiviral active against circulating influenza strains is considered an adjunct to vaccination for control and prevention of influenza in certain individuals.

CDC and other experts recommend that adamantanes (amantadine, rimantadine) not be used for prevention of influenza in the US until susceptibility to these antiviral agents has been reestablished in circulating influenza A viruses.

Consider viral surveillance data available from local and state health departments and the CDC when selecting an antiviral for prophylaxis of influenza. The most appropriate antiviral for prevention of influenza is selected based on information regarding the likelihood that the influenza strain is susceptible and the known adverse effects of the drug. Strains of circulating influenza viruses and the antiviral susceptibility of these strains constantly evolve.

CDC issues recommendations concerning use of antivirals for prophylaxis of influenza, and these recommendations are updated as needed during each influenza season. Information regarding influenza surveillance and updated recommendations for prevention of seasonal influenza are available from CDC at [Web].

Avian Influenza A Virus Infections

Has been recommended as alternative for treatment or prophylaxis of avian influenza A virus infections in certain situations.

CDC and WHO recommend use of a neuraminidase inhibitor (oseltamivir, zanamivir) for treatment or prophylaxis of avian influenza A infections.

If neuraminidase inhibitors unavailable, use of amantadine or rimantadine might be considered an alternative if local surveillance data indicate the strain is known or likely to be susceptible. Avian influenza A (H5N1) and avian influenza A (H7N9) generally have been resistant to adamantanes.

Parkinsonian Syndrome

Symptomatic treatment of parkinsonian syndrome, including idiopathic parkinson disease, postencephalitic parkinsonism, and parkinsonism resulting from carbon monoxide intoxication or cerebral arteriosclerosis.

Has been used as monotherapy or adjunctive therapy in the treatment of parkinson disease.

Levodopa is currently the most effective drug for relieving motor symptoms of parkinson disease; however, long-term use associated with motor complications. Strategies for reducing these complications include adjusting dosage of levodopa, adding other antiparkinsonian agents (e.g., amantadine), or initiating other antiparkinsonian agents first to postpone use of levodopa.

While amantadine may be effective as initial monotherapy, particularly for resting tremors, symptomatic benefits may last only a few weeks.

As adjunctive therapy, amantadine is typically used for levodopa-induced dyskinesia; however, evidence of efficacy is mixed and based principally on small randomized controlled studies.

Drug-induced Extrapyramidal Effects

Symptomatic treatment of antipsychotic-induced extrapyramidal effects.

Generally used in patients with antipsychotic-induced pseudoparkinsonism; appears to be as effective as anticholinergic agents. May be particularly useful when anticholinergics should be avoided (e.g., in patients with glaucoma or urinary retention).

May be effective in some patients with antipsychotic-induced akathisia; however, evidence is limited and tolerance may occur.

Amantadine Dosage and Administration

Administration

Oral Administration

Administer orally as conventional (immediate-release) tablets, capsules, or oral solution. Also available in extended-release tablet or capsule formulations for the treatment of parkinson disease.

Conventional Preparations

Commercially available as tablets or liquid-filled capsules containing 100 mg of the drug and as an oral solution containing 50 mg/5 mL.

Extended-release Capsules

Administer orally once daily at bedtime with or without food.

Swallow capsules whole; do not crush, chew, or divide. If necessary, may open capsules and sprinkle contents on a small amount (e.g., teaspoonful) of soft food such as applesauce; swallow drug/food mixture immediately without chewing. Do not store mixture for later use.

Extended-release Tablets

Administer orally once daily in the morning with or without food.

Swallow tablets whole; do not crush, chew, or divide.

Dosage

Available as amantadine hydrochloride; dosage of conventional preparations expressed in terms of amantadine hydrochloride and dosage of extended-release preparations expressed in terms of amantadine.

Reduced dosage recommended in geriatric adults ≥65 years of age and in patients with renal impairment. (See Special Populations under Dosage and Administration.) Reduction of usual dosage also may be needed in patients with CHF, peripheral edema, or orthostatic hypotension.

Pediatric Patients

Treatment of Seasonal Influenza A Virus Infections
Oral

Children 1–9 years of age: Manufacturer recommends 4.4–8.8 mg/kg (up to 150 mg) daily as conventional preparations. AAP recommends 5 mg/kg (up to 150 mg) daily in 2 divided doses.

Children 9–12 years of age: Manufacturer recommends 100 mg twice daily as conventional preparations.

Children ≥10 years of age: AAP recommends 5 mg/kg daily in 2 divided doses in those weighing <40 kg or 100 mg twice daily in those weighing ≥40 kg as conventional preparations.

Children and adolescents ≥12 years of age: Manufacturer recommends 200 mg once daily or 100 mg twice daily as conventional preparations.

Initiate as soon as possible, preferably within 24–48 hours after onset of symptoms, and continue for 24–48 hours after symptoms disappear.

Prevention of Seasonal Influenza A Virus Infections
Oral

Children 1–9 years of age: Manufacturer recommends 4.4–8.8 mg/kg (up to 150 mg) daily as conventional preparations. AAP recommends 5 mg/kg (up to 150 mg) daily in 2 divided doses.

Children 9–12 years of age: Manufacturer recommends 100 mg twice daily as conventional preparations.

Children ≥10 years of age: AAP recommends 5 mg/kg daily in 2 divided doses in those weighing <40 kg or 100 mg twice daily in those weighing ≥40 kg as conventional preparations.

Children and adolescents ≥12 years of age: Manufacturer recommends 200 mg once daily or 100 mg twice daily as conventional preparations.

Alternatively, AAP states children weighing >20 kg can receive 100 mg daily.

Continue prophylaxis for at least 10 days following a known exposure. If used as adjunct to influenza vaccination, continue for 2–4 weeks after vaccine is given to provide prophylaxis until protective antibody response develops. (See Interactions.)

Adults

Treatment of Seasonal Influenza A Virus Infections
Oral

Adults <65 years of age: 200 mg once daily or 100 mg twice daily as conventional preparations.

Dosage may be decreased to 100 mg daily in those who experience CNS or other toxicities with 200 mg daily; relative efficacy of lower dosage not elucidated.

Initiate as soon as possible, preferably within 24–48 hours after onset of symptoms, and continue for 24–48 hours after symptoms disappear.

Prevention of Seasonal Influenza A Virus Infections
Oral

Adults <65 years of age: 200 mg once daily or 100 mg twice daily as conventional preparations.

Dosage may be decreased to 100 mg daily in those who experience CNS or other toxicities with 200 mg daily; relative efficacy of lower dosage not elucidated.

Continue prophylaxis for at least 10 days following a known exposure. If used as adjunct to influenza vaccination, continue for 2–4 weeks after vaccine is given to provide prophylaxis until protective antibody response develops. (See Interactions.)

Parkinsonian Syndrome
Oral

Conventional tablets, capsules, or oral solution: Usually, 100 mg twice daily. In patients with serious illness or receiving high dosages of other antiparkinsonian agents, initial dosage of 100 mg daily recommended; after one to several weeks, may increase to 100 mg twice daily if necessary. Occasionally, patients may benefit from an increase up to 400 mg daily in divided doses; monitor patients receiving such high dosages closely.

If loss of effectiveness occurs after a few months of therapy, may increase dosage to 300 mg daily to regain benefit; alternatively, some patients may respond to temporary discontinuance of drug for several weeks, followed by reinstitution of therapy.

Extended-release capsules: Initially, 137 mg once daily at bedtime. After 1 week, increase to recommended dosage of 274 mg (given as two 137-mg capsules) once daily at bedtime. When discontinuing therapy in patients who have been receiving the drug for >4 weeks, reduce dosage by half, if possible, during final week of dosing. If a dose is missed, take next dose at regularly scheduled time.

Extended-release tablets: Initially, 129 mg once daily in the morning. May increase in weekly intervals to maximum recommended dosage of 322 mg once daily (given as a 129-mg and a 193-mg tablet) in the morning. When discontinuing therapy, reduce dosage to 129 mg daily for 1–2 weeks before drug is discontinued. If a dose is missed, take next dose at regularly scheduled time.

Drug-induced Extrapyramidal Effects
Oral

Conventional tablets, capsules, or oral solution: Usually, 100 mg twice daily; may increase up to 300 mg daily (in divided doses) if necessary.

Extended-release tablets: Initially, 129 mg once daily in the morning. May increase in weekly intervals to maximum recommended dosage of 322 mg once daily (given as a 129-mg and a 193-mg tablet) in the morning. When discontinuing therapy, reduce dosage to 129 mg daily for 1–2 weeks before drug is discontinued. If a dose is missed, take next dose at regularly scheduled time.

Prescribing Limits

Pediatric Patients

Oral

Treatment or Prevention of Seasonal Influenza A Virus Infections in children 1–9 years of age: Maximum 150 mg daily as conventional preparations.

Adults

Oral

Extended-release capsules: Do not exceed maximum recommended dosages in patients with renal impairment. (See Renal Impairment under Dosage and Administration.)

Extended-release tablets: Maximum daily dosage of 322 mg in all patients. (See Renal Impairment under Dosage and Administration.)

Special Populations

Renal Impairment

Table 1: Dosage of Conventional Capsules, Tablets, and Oral Solution in Adults with Renal Impairment126

Clcr (mL/minute per 1.73 m2)

Dosage

30–50

200 mg on first day, then 100 mg daily

15–29

200 mg on first day, then 100 mg every other day

<15

200 mg every 7 days

Hemodialysis patients

200 mg every 7 days

Table 2: Dosage of Extended-release Capsules in Adults with Renal Impairment227

Clcr (mL/minute per 1.73 m2)

Dosage

30–59

Initially, 68.5 mg once daily at bedtime; increase if needed after 1 week up to maximum of 137 mg once daily at bedtime

15–29

68.5 mg once daily at bedtime

<15

Contraindicated

Table 3: Dosage of Extended-release Tablets in Adults with Renal Impairment228

Clcr (mL/minute per 1.73 m2)

Dosing Interval and Titration Interval

30–59

Modify frequency of dosing to once every 48 hours; modify interval between dosage increases to every 3 weeks

15–29

Modify frequency of dosing to once every 96 hours; modify interval between dosage increases to every 4 weeks

<15

Use contraindicated

Geriatric Patients

100 mg once daily for treatment or prophylaxis of influenza A virus infection in those ≥65 years of age. Dosage may need to be further reduced in some patients.

Cautions for Amantadine

Contraindications

  • Known hypersensitivity to amantadine or any ingredient in the formulation.

  • Extended-release capsules and tablets are contraindicated in patients with end-stage renal disease.

Warnings/Precautions

Warnings

Fatalities, Acute Toxicity, and Suicide Risk

Fatalities reported following overdosage. Overdosage has resulted in cardiac (arrhythmia, tachycardia, hypertension), respiratory, renal, or CNS toxicity; may be related to anticholinergic effects of the drug.

Deaths due to drug accumulation (overdosage) reported in patients with renal impairment who received higher than recommended dosages for their degree of renal impairment. (See Renal Impairment under Cautions.)

Suicide attempts (including some fatalities) reported rarely; many patients received short courses of the drug for influenza treatment or prophylaxis.

Suicide ideation or attempts reported in patients with or without a prior history of psychiatric disorders. Amantadine can exacerbate symptoms in patients with a history of psychiatric disorders or substance abuse. Patients with suicidal tendencies may exhibit abnormal mental states including disorientation, confusion, depression, personality changes, agitation, aggressive behavior, hallucinations, paranoia, other psychotic reactions, somnolence, or insomnia.

Monitor for depression and suicidal ideation/behavior during therapy. Weigh risks versus benefits in patients with a history of suicidality or depression.

Use with caution in patients with psychosis or severe psychoneurosis.

Lowest reported lethal dose is 1 g. Prescriptions should be written for smallest quantity consistent with good patient management.

Hallucinations and Psychotic Behavior

Hallucinations and other psychiatric symptoms or behaviors reported during treatment or when drug was abruptly discontinued in patients with parkinson disease.

Use generally not advised in patients with major psychotic disorders because of risk of exacerbating psychosis.

Monitor for hallucinations during therapy, particularly after initiation and when dosage is increased or decreased.

Falling Asleep During Activities of Daily Living and Somnolence

Episodes of falling asleep while engaged in activities of daily living (e.g., driving) reported in patients with parkinson disease; sometimes resulted in accidents. Some patients perceived no warning signs (e.g., excessive drowsiness) and believed they were alert immediately prior to the event.

Ask patients about any factors that may increase the risk of somnolence (e.g., concomitant sedating drugs or alcohol, presence of sleep disorders).

In general, discontinue therapy if a patient develops daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating). If the drug is continued, advise patient not to drive and to avoid other potentially dangerous activities. (See Advice to Patients.) Insufficient information to establish whether dosage reduction will eliminate this adverse event.

CNS Effects

Patients with a history of epilepsy or other seizure disorders should be observed closely for possible increased seizure activity.

Cardiovascular Effects

CHF reported; monitor patients with a history of CHF or peripheral edema. Dosage adjustment may be needed.

Orthostatic hypotension and dizziness may occur. Monitor patients for signs and symptoms of orthostatic hypotension, particularly after initiation of therapy and when dosage is increased. Concomitant use of extended-release preparations with alcohol not recommended.

Use with caution and adjust dosage as needed in patients with CHF, peripheral edema, or orthostatic hypotension.

Ocular Effects

May cause mydriasis; do not use in patients with untreated angle-closure glaucoma.

Sensitivity Reactions

Allergic reactions, including anaphylactic reaction, rash, eczematoid dermatitis, photosensitization, pruritus, and diaphoresis, reported rarely.

Use with caution in patients with recurrent eczematoid dermatitis.

General Precautions

Abrupt Withdrawal of Therapy

Do not abruptly discontinue amantadine in patients with parkinsonian syndrome; some patients have developed parkinsonian crises after abrupt discontinuance of the drug. Abrupt discontinuance also may precipitate delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, and slurred speech.

Hyperpyrexia and Confusion

A symptom complex resembling neuroleptic malignant syndrome (NMS; e.g., elevated temperature, muscular rigidity, altered consciousness, autonomic instability) reported; associated with rapid dosage reduction or withdrawal of drugs that increase central dopaminergic tone. Observe patients closely when dosage is reduced or the drug discontinued; this precaution is especially important in patients receiving concomitant therapy with an antipsychotic agent. (See Abrupt Withdrawal of Therapy under Cautions.)

Impulse Control and Compulsive Behaviors

Intense urges (e.g., urge to gamble, increased sexual urges, intense urges to spend money uncontrollably, other intense urges) and inability to control these urges reported in some patients receiving drugs that increase central dopaminergic tone. In some cases, urges stopped when dosage was reduced or drug was discontinued.

Because patients may not recognize these behaviors as abnormal, ask patients and/or their caregivers whether new or increased gambling urges, sexual urges, uncontrolled spending, or other urges have developed during amantadine treatment; advise them of the importance of reporting such urges. Consider reducing dosage or discontinuing amantadine if a patient develops such urges while receiving the drug. (See Advice to Patients.)

Melanoma

Epidemiologic studies indicate patients with parkinsonian syndrome have a twofold to sixfold higher risk of developing melanoma than the general population. Unclear whether increased risk is due to parkinsonian syndrome or other factors (e.g., drugs used to treat parkinson disease).

Monitor for melanoma frequently and on a regular basis. Periodic skin examinations by appropriately qualified individuals (e.g., dermatologists) recommended.

Resistance

Seasonal influenza A (H3N2) and influenza A (H1N1)pdm09 viruses circulating during recent influenza seasons have been resistant to adamantanes (amantadine, rimantadine).

CDC and other experts recommend that adamantanes (amantadine, rimantadine) not be used for treatment or prevention of influenza in the US until susceptibility to these antiviral agents has been reestablished in circulating influenza A viruses.

Differential Diagnosis

Serious bacterial infections may present with influenza-like symptoms or may coexist with or occur as complications of influenza. No evidence that amantadine prevents such complications.

Not effective for treatment or prophylaxis of viral respiratory tract illnesses other than those due to susceptible influenza A virus.

Influenza Vaccination

Not a substitute for annual vaccination with a seasonal influenza vaccine (influenza virus vaccine inactivated, influenza vaccine recombinant, influenza vaccine live intranasal).

Although antivirals used for treatment or prevention of influenza, including amantadine, may be used concomitantly with or at any time before or after influenza virus vaccine inactivated, these antivirals may inhibit the vaccine virus contained in influenza vaccine live intranasal. (See Specific Drugs under Interactions.)

Specific Populations

Pregnancy

No adequate data in pregnant women; in animal studies, adverse developmental effects (e.g., embryolethality, malformations, reduced fetal body weight) observed.

Lactation

Do not use in nursing women. Distributed into milk.

Pediatric Use

Safety and efficacy not established in neonates or infants <1 year of age.

Geriatric Use

Substantially eliminated by the kidneys. Consider age-related decreases in renal function and the potential for concomitant disease when selecting dosage. (See Geriatric Patients under Dosage and Administration.)

Hepatic Impairment

Use with caution in patients with liver disease. Increased concentrations of liver enzymes reported.

Renal Impairment

Deaths due to drug accumulation (overdosage) reported in patients with renal impairment who received amantadine dosage higher than recommended for their degree of renal impairment. Use reduced dosage in those with Clcr ≤50 mL/minute. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Nausea, dizziness (lightheadedness), insomnia.

Interactions for Amantadine

Specific Drugs

Drug

Interaction

Comments

Alcohol

Potential for increased CNS effects (dizziness, confusion, lightheadedness, orthostatic hypotension)

Avoid excessive usage of alcohol

Manufacturers of extended-release preparations state concomitant use not recommended

Anticholinergic agents

Potential for increased adverse anticholinergic and CNS effects

Dosage adjustment of both drugs may be needed

Antihistamines

Potential for increased CNS effects

Antipsychotic agents

Possible increased risk of NMS (see Neuroleptic Malignant Syndrome under Cautions)

Observe closely if amantadine dosage is reduced or amantadine discontinued

CNS agents

Potential for increased adverse effects

Use with caution

CNS stimulants

Possibility of additive CNS stimulant effects

Use with caution

Co-trimoxazole

Toxic delirium reported in an individual who received co-trimoxazole and amantadine concomitantly

Hydrochlorothiazide

Fixed combination of triamterene and hydrochlorothiazide (co-triamterzide): Possible increased amantadine plasma concentrations

Influenza virus vaccines

Influenza virus vaccine inactivated: Amantadine does not interfere with the antibody response to the vaccine

Influenza vaccine live intranasal: Potential interference with antibody response to the live vaccine; no specific studies

Influenza virus vaccine inactivated: May be administered concomitantly with or at any interval before or after amantadine

Influenza vaccine live intranasal: Do not administer the live vaccine until ≥48 hours after amantadine is discontinued; do not administer amantadine until ≥2 weeks after administration of the vaccine, unless medically indicated; if amantadine given within 2 weeks after the vaccine, repeat vaccine dose ≥48 hours after last antiviral dose; alternatively, if amantadine given 2 days before to 14 days after the vaccine, revaccinate using the parenteral inactivated vaccine or parenteral recombinant vaccine

Quinidine or quinine

Reduction in renal clearance of amantadine

Thioridazine

Worsened tremor in geriatric patients with parkinsonian syndrome reported; not known whether similar effect could occur with other phenothiazines

Urine acidifying drugs

Possible increased elimination of amantadine

Amantadine Pharmacokinetics

Absorption

Bioavailability

Well absorbed from GI tract; peak plasma concentrations achieved in 2–4 hours following administration of conventional preparations.

Onset

When used for parkinsonian syndrome, onset of action usually within 48 hours.

Plasma Concentrations

Peak plasma concentrations are directly related to amantadine hydrochloride dosage up to 200 mg daily; dosages >200 mg daily may result in a greater than proportional increase in peak plasma concentration.

Following oral administration of the extended-release tablet, dose-proportional pharmacokinetics observed over dose range of 129–322 mg. Peak plasma concentrations achieved in a median of 7.5 hours.

Following oral administration of the extended-release capsule, dose-proportional pharmacokinetics observed over dose range of 68.5–274 mg. After a single bedtime dose, median time to reach peak plasma concentration was approximately 12 hours and steady-state concentrations were achieved 4 days following initiation of therapy.

There appears to be a relationship between plasma concentrations of amantadine and toxicity. As concentrations increase, toxicity becomes more prevalent.

Food

Extended-release tablets: Food does not affect rate or extent of absorption.

Extended-release capsules: No effect of food on pharmacokinetics observed; administration of capsule contents with applesauce also had no effect on pharmacokinetics.

Special Populations

Plasma concentrations increased in patients with renal impairment.

Plasma concentrations in geriatric patients receiving a dosage of 100 mg daily approximate those attained in younger adults receiving a dosage of 200 mg daily.

Distribution

Extent

Not fully characterized.

Distributed into nasal secretions, erythrocytes, CSF, and milk.

Plasma Protein Binding

67%.

Elimination

Metabolism

Undergoes N-acetylation.

Elimination Route

Principally excreted unchanged in urine by glomerular filtration and tubular secretion; about 5–15% excreted in urine as acetylamantadine.

Only minimally removed by hemodialysis.

Half-life

16 hours (range 9–31 hours).

Special Populations

Half-life prolonged in patients with renal impairment (Clcr <40 mL/minute). Half-life of 18.5–81.3 hours reported in patients with Clcr 13.7–43.1 mL/minute; half-life averages 8.3 days (range: 7–10.3 days) in patients undergoing chronic hemodialysis.

Half-life prolonged in healthy geriatric adults. Half-life of 29 hours (range: 20–41 hours) reported in geriatric men 60–76 years of age.

Stability

Storage

Oral

Conventional Capsules

20–25°C; in tight, light-resistant containers.

Conventional Tablets

20–25°C (may be exposed to 15–30°C); in tight, light-resistant containers.

Extended-release Capsules

20–25°C (may be exposed to 15–30°C).

Extended-release Tablets

20–25°C (may be exposed to 15–30°C); in tight containers.

Oral Solution

20–25°C (may be exposed to 15–30°C); in tight containers.

Actions and Spectrum

  • Adamantane-derivative (a symmetric tricyclic amine); structurally related to rimantadine.

  • Has antiviral activity against some strains of influenza A, including susceptible H1N1, H2N2, and H3N2.

  • Has little or no activity against influenza B.

  • Beginning in the 2005–2006 influenza season, most influenza A (H3N2) strains circulating in the US were resistant to amantadine and rimantadine. Resistance to amantadine and rimantadine among seasonal influenza A (H3N2) circulating during recent influenza seasons has remained high.

  • Although amantadine and rimantadine were active against most seasonal influenza A (H1N1) viruses circulating in the US during the 2008–2009 and 2009–2010 influenza seasons, the influenza A (H1N1)pdm09 virus circulating during recent influenza seasons is resistant to amantadine and rimantadine.

  • Although some strains of avian influenza A (H5N1) have been susceptible to amantadine, avian influenza A virus strains tested (including H5N1 and H7N9) generally are resistant to adamantanes.

  • Inhibits viral replication by interfering with the influenza A virus M2 protein, an integral membrane protein.

  • Strains of influenza A virus with reduced susceptibility to amantadine have been produced in vitro and have emerged during therapy with the drug.

  • Amantadine-resistant influenza A viruses also are resistant to rimantadine and vice versa.

  • Mechanism of action in treatment of parkinsonian syndrome and drug-induced extrapyramidal reactions unknown. May enhance extracellular concentrations of dopamine at dopaminergic neurons, directly stimulating the dopamine receptor, or increasing sensitivity at receptors.

Advice to Patients

  • Risk of CNS effects and blurred vision; use caution when alertness and motor coordination is needed.

  • Advise patients with parkinsonian syndrome to gradually increase physical activity as symptoms improve.

  • Importance of avoiding excessive alcohol usage.

  • Importance of not getting up suddenly from a sitting or lying position; notify clinician if dizziness or lightheadedness occurs.

  • Importance of notifying clinician if mood/mental changes, swelling of extremities, difficulty urinating, and/or dyspnea occur.

  • Importance of taking amantadine as prescribed; importance of not taking more drug than prescribed. Importance of consulting clinician if there is no improvement after a few days or if drug appears less effective after a few weeks.

  • Importance of seeking immediate medical attention for suspected overdose.

  • Importance of consulting clinician before discontinuing amantadine.

  • Importance of informing clinician if new or increased gambling urges, sexual urges, or other urges occur while receiving amantadine.

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal products, as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Amantadine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules, liquid-filled

100 mg*

Amantadine Hydrochloride Capsules

Capsules, extended-release

68.5 mg (of amantadine)

Gocovri

Adamas

137 mg (of amantadine)

Gocovri

Adamas

Solution

50 mg/5 mL*

Amantadine Hydrochloride Oral Solution

Tablets

100 mg*

Amantadine Hydrochloride Tablets

Tablets, extended-release

129 mg (of amantadine)

Osmolex ER

Vertical

193 mg (of amantadine)

Osmolex ER

Vertical

258 mg (of amantadine)

Osmolex ER

Vertical

AHFS DI Essentials™. © Copyright 2022, Selected Revisions February 14, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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Frequently asked questions

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