amantadine (Rx)

Brand and Other Names:Osmolex ER, Gocovri

Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

capsule or tablet, immediate-release (generic)

  • 100mg

syrup (generic)

  • 50mg/5mL

capsule, extended-release (Gocovri)

  • 68.5mg
  • 137mg

tablet, extended-release (Osmolex ER)

  • 129mg
  • 193mg
  • 258mg

Parkinson Disease

Immediate-release tablet/capsule or syrup

  • Indicated for the treatment of idiopathic Parkinson disease (Paralysis Agitans), postencephalitic Parkinsonism, and symptomatic Parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication
  • Monotherapy: 100 mg/day PO initially; may be increased to 100 mg q12hr after at least 1 week; may increase dose up to 400 mg/day in divided doses
  • Serious concomitant illness or those receiving high doses of other antiparkinson drugs: 100 mg PO qDay; may increase to 100 mg q12hr, if needed, after one to several week

Extended-release tablet (Osmolex ER)

  • Indicated for treatment of Parkinson disease
  • 129 mg PO qDay qAM initially; may increase dose in weekly intervals, not to exceed 322 mg/day (one 129-mg and 193-mg tablet)
  • For patients unable to tolerate >100 mg/day of immediate-release amantadine, there is no equivalent dose or dosing regimen of extended-release tablets

Extended-release capsule (Gocovri)

  • Indicated for adjunctive treatment to levodopa/carbidopa for Parkinson disease in patients experiencing “off” episodes
  • 137 mg PO qHS; increase to recommended dose of 274 mg PO qHS after 1 week

Dyskinesia Associated with Parkinson Disease

Gocovri only

Indicated for dyskinesia in patients with Parkinson disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications

137 mg PO qHS; increase to recommended dose of 274 mg PO qHS after 1 week

Drug-induced Extrapyramidal Symptoms

Indicated in the treatment of drug-induced extrapyramidal reactions

Immediate-release tablet/capsule or syrup

  • 100 mg PO q12hr; not to exceed 300 mg/day

Extended-release tablet (Osmolex ER)

  • 129 mg PO qDay qAM initially; may increase dose in weekly intervals, not to exceed 322 mg/day (one 129-mg and 193-mg tablet)
  • For patients unable to tolerate >100 mg/day of immediate-release amantadine, there is no equivalent dose or dosing regimen of extended-release tablets

Influenza A Prophylaxis or Treatment

Immediate-release tablet/capsule or syrup only

NOTE: Because of resistance, amantadine is no longer recommended for prophylaxis or treatment of influenza A; refer to current CDC recommendations

200 mg PO as a single daily dose; may split daily dosage to one 100 mg q12hr; if central nervous system effects develop in once-a-day dosage, a split dosage schedule may reduce such complaints

Dosage Modifications

Renal impairment

  • Immediate-release tablet/capsule or syrup
    • 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 or hemodialysis: 200 mg PO weekly
  • Extended-release capsule (Gocovri)
    • Mild (CrCl 60-89 ml/min/1.73 m2): No dosage adjustment necessary
    • Moderate (CrCl 30-59 mL/min/1.73m2): 68.5 mg qHS initially; may increase to 137 mg qHS after 1 week if necessary; not to exceed 137 mg qHS
    • Severe (CrCl 15-29 mL/min/1.73m2): 68.5 mg qHS
    • End-stage renal disease (CrCl <15 mL/min/1.73m2): Contraindicated
    • Hemodialysis: Inefficiently removed
  • Extended-release tablet (Osmolex ER)
    • No modifications for the recommended initial and maximum dose in renal impairment; however, modifications are recommended for the titration interval and frequency of dosing in patients with moderate and severe renal impairment
    • Mild (CrCl 60-89 mL/min/1.73 m2): May increase dose weekly; take 1 dose qDay
    • Moderate (CrCl 30-59 mL/min/1.73 m2): May increase q3Weeks; take 1 dose q48hr
    • Severe (CrCl 15-29 mL/min/1.73 m2): May increase q4Weeks; take 1 dose q96hr
    • End-stage renal disease (CrCl<15 mL/min/1.73 m2): Contraindicated
    • Monitor changes in renal function, especially in those with severe renal impairment receiving a daily dosage of 322 mg

Dosing Considerations

Amantadine immediate- or extended-release products are not interchangeable

Concomitant use of alcohol when using amantadine extended-release is not recommended owing to increased CNS effects and may result in dose-dumping

Osmolex ER: Do not discontinue abruptly; gradually reduce dose from higher doses to 129 mg daily for 1-2 weeks before discontinuing

Gocovri: Do not discontinue abruptly; to stop therapy in patients who have been on the drug for more than 4 weeks, their dose should typically, if possible, be reduced by half for their final week of dosing

Dosage Forms & Strengths

capsule or tablet, immediate-release (generic)

  • 100mg

syrup (generic)

  • 50mg/5mL

Influenza A Prophylaxis or Treatment

NOTE: Because of resistance, amantadine is no longer recommended for prophylaxis or treatment of influenza A; refer to current CDC recommendations

1-9 years: 2-4 mg/kg/day PO in single dose or divided q12 hr; not to exceed 150 mg/day

9-12 years: 100 mg PO q12hr; 100 mg/day has not been studied in this pediatric population; continue treatment for at least 10 days following a known exposure

Parkinson Disease

>65 years: Therapy should be based on renal function

Influenza A Prophylaxis or Treatment

≥65 years: 100 mg PO as a single dose

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Interactions

Interaction Checker

and amantadine

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              Serious - Use Alternative (8)

              • amisulpride

                amisulpride, amantadine. Either decreases effects of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid use of amisulpride, a dopamine receptor antagonist, with dopamine agonists.

              • ethanol

                ethanol will increase the level or effect of amantadine by Other (see comment). Avoid or Use Alternate Drug. Coadministration of amantadine with alcohol is not recommended, as it may increase the potential for CNS effects such as dizziness, confusion, lightheadedness, and orthostatic hypotension. Alcohol may result in dose-dumping if coadministered with extended-release amantadine.

              • influenza virus vaccine quadrivalent, intranasal

                amantadine, influenza virus vaccine quadrivalent, intranasal. Other (see comment). Avoid or Use Alternate Drug. Comment: Because of its antiviral properties, amantadine may interfere with the efficacy of live attenuated influenza vaccines (LAIV). Coadministration of LAIV and amantadine is not recommended. Inactivated influenza vaccines may be used, as appropriate.

              • mefloquine

                mefloquine increases toxicity of amantadine by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

              • metoclopramide intranasal

                metoclopramide intranasal, amantadine. dopaminergic effects. Avoid or Use Alternate Drug. Opposing effects of metoclopramide and the interacting drug on dopamine. Potential exacerbation of symptoms (eg, parkinsonian symptoms) or decreased therapeutic effects of metoclopramide.

              • olopatadine intranasal

                amantadine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

              • tafenoquine

                tafenoquine will increase the level or effect of amantadine by Other (see comment). Avoid or Use Alternate Drug. Tafenoquine inhibits organic cation transporter-2 (OCT2) and multidrug and toxin extrusion (MATE) transporters in vitro. Avoid coadministration with OCT2 or MATE substrates. If coadministration cannot be avoided, monitor for substrate-related toxicities and consider dosage reduction if needed based on product labeling of the coadministered drug.

              • trilaciclib

                trilaciclib will increase the level or effect of amantadine by Other (see comment). Avoid or Use Alternate Drug. Avoid coadministration of trilaciclib (OCT2, MATE1, and MATE-2K inhibitor) with substrates where minimal increased concentration in kidney or blood may lead to serious or life-threatening toxicities.

              Monitor Closely (60)

              • acetazolamide

                acetazolamide will decrease the level or effect of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Excretion rate of amantadine increases rapidly when urine is acidic, administration of urine acidifying drugs may increase elimination of amantadine from the body. Monitor for efficacy of amantadine.

              • aclidinium

                aclidinium, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • amifampridine

                amantadine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

              • anticholinergic/sedative combos

                anticholinergic/sedative combos, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • atropine

                atropine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • atropine IV/IM

                atropine IV/IM, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced CNS side effects.

              • belladonna alkaloids

                belladonna alkaloids, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • belladonna and opium

                belladonna and opium, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • benztropine

                benztropine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • brinzolamide

                brinzolamide will decrease the level or effect of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Excretion rate of amantadine increases rapidly when urine is acidic, administration of urine acidifying drugs may increase elimination of amantadine from the body. Monitor for efficacy of amantadine.

              • bupropion

                amantadine, bupropion. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential CNS toxicity d/t synergistic central dopamine effect.

              • calcium acetate

                calcium acetate will increase the level or effect of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Urine pH changes towards alkalinic conditions may lead to an accumulation of amantadine with a possible increase in adverse reactions. Monitor for adverse reactions of amantadine.

              • calcium carbonate

                calcium carbonate will increase the level or effect of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Urine pH changes towards alkalinic conditions may lead to an accumulation of amantadine with a possible increase in adverse reactions. Monitor for adverse reactions of amantadine.

              • calcium citrate

                calcium citrate will increase the level or effect of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Urine pH changes towards alkalinic conditions may lead to an accumulation of amantadine with a possible increase in adverse reactions. Monitor for adverse reactions of amantadine.

              • cyclizine

                cyclizine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • cyclobenzaprine

                cyclobenzaprine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • daridorexant

                amantadine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

              • darifenacin

                darifenacin, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • dicyclomine

                dicyclomine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • difelikefalin

                difelikefalin and amantadine both increase sedation. Use Caution/Monitor.

              • diphenhydramine

                diphenhydramine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • dorzolamide

                dorzolamide will decrease the level or effect of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Excretion rate of amantadine increases rapidly when urine is acidic, administration of urine acidifying drugs may increase elimination of amantadine from the body. Monitor for efficacy of amantadine.

              • erdafitinib

                erdafitinib increases levels of amantadine by decreasing renal clearance. Modify Therapy/Monitor Closely. Consider alternatives that are not OCT2 substrates or consider reducing the dose of OCT2 substrates based on tolerability.

              • fesoterodine

                fesoterodine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • flavoxate

                flavoxate, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • glycopyrrolate

                glycopyrrolate, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • glycopyrrolate inhaled

                glycopyrrolate inhaled increases levels of amantadine by unknown mechanism. Use Caution/Monitor.

                glycopyrrolate inhaled, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • henbane

                henbane, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced CNS side effects.

              • homatropine

                homatropine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced CNS side effects.

              • hyoscyamine

                hyoscyamine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • hyoscyamine spray

                hyoscyamine spray, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced CNS side effects.

              • ipratropium

                ipratropium, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • lurasidone

                lurasidone increases effects of amantadine by Other (see comment). Use Caution/Monitor. Comment: Antipsychotics may diminish the therapeutic effect of anti-parkinson's agents.

              • meclizine

                meclizine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • memantine

                memantine, amantadine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Combination may lead to additive adverse effects. If coadministration cannot be avoided, monitor for increased adverse effects such as agitation, dizziness and other CNS events.

              • methazolamide

                methazolamide will decrease the level or effect of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Excretion rate of amantadine increases rapidly when urine is acidic, administration of urine acidifying drugs may increase elimination of amantadine from the body. Monitor for efficacy of amantadine.

              • methscopolamine

                methscopolamine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • onabotulinumtoxinA

                onabotulinumtoxinA, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • oxybutynin

                oxybutynin, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • oxybutynin topical

                oxybutynin topical, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • oxybutynin transdermal

                oxybutynin transdermal, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • potassium citrate

                potassium citrate will increase the level or effect of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Urine pH changes towards alkalinic conditions may lead to an accumulation of amantadine with a possible increase in adverse reactions. Monitor for adverse reactions of amantadine.

              • propantheline

                propantheline, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • quinidine

                quinidine will increase the level or effect of amantadine by decreasing renal clearance. Use Caution/Monitor. Coadministration of quinine or quinidine with amantadine was shown to reduce the renal clearance of amantadine by ~30%.

              • quinine

                quinine will increase the level or effect of amantadine by decreasing renal clearance. Use Caution/Monitor. Coadministration of quinine or quinidine with amantadine was shown to reduce the renal clearance of amantadine by ~30%.

              • scopolamine

                scopolamine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • sodium bicarbonate

                sodium bicarbonate will increase the level or effect of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Urine pH changes towards alkalinic conditions may lead to an accumulation of amantadine with a possible increase in adverse reactions. Monitor for adverse reactions of amantadine.

              • solifenacin

                solifenacin, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • solriamfetol

                amantadine and solriamfetol both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor.

              • sulfamethoxazole

                sulfamethoxazole increases levels of amantadine by decreasing elimination. Use Caution/Monitor. Coadministration may impair renal clearance of amantadine, resulting in higher plasma concentrations.

              • tiotropium

                tiotropium, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • tolterodine

                tolterodine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • triamterene

                triamterene increases levels of amantadine by decreasing elimination. Use Caution/Monitor.

              • trihexyphenidyl

                trihexyphenidyl, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • trimethoprim

                trimethoprim increases levels of amantadine by decreasing elimination. Use Caution/Monitor. Coadministration may impair renal clearance of amantadine, resulting in higher plasma concentrations.

              • trospium chloride

                trospium chloride, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • ublituximab

                ublituximab decreases effects of amantadine by immunosuppressive effects; risk of infection. Use Caution/Monitor.

              • umeclidinium bromide

                umeclidinium bromide, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • umeclidinium bromide/vilanterol inhaled

                umeclidinium bromide/vilanterol inhaled, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

              • vandetanib

                vandetanib increases levels of amantadine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Vandetanib inhibits the uptake of substrates of organic cation transporter type 2 (OCT2).

              Minor (19)

              • armodafinil

                amantadine, armodafinil. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • atropine IV/IM

                atropine IV/IM increases levels of amantadine by unknown mechanism. Minor/Significance Unknown.

              • caffeine

                amantadine, caffeine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • dexmethylphenidate

                amantadine, dexmethylphenidate. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • dextroamphetamine

                amantadine, dextroamphetamine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • influenza virus vaccine quadrivalent

                amantadine decreases effects of influenza virus vaccine quadrivalent by Other (see comment). Minor/Significance Unknown. Comment: Because of its antiviral properties, amantadine may interfere with the efficacy of live attenuated influenza vaccines (LAIV). Coadministration of LAIV and amantadine is not recommended. Inactivated influenza vaccines may be used, as appropriate.

              • influenza virus vaccine quadrivalent, cell-cultured

                amantadine decreases effects of influenza virus vaccine quadrivalent, cell-cultured by Other (see comment). Minor/Significance Unknown. Comment: Because of its antiviral properties, amantadine may interfere with the efficacy of live attenuated influenza vaccines (LAIV). Coadministration of LAIV and amantadine is not recommended. Inactivated influenza vaccines may be used, as appropriate.

              • influenza virus vaccine quadrivalent, recombinant

                amantadine decreases levels of influenza virus vaccine quadrivalent, recombinant by Other (see comment). Minor/Significance Unknown. Comment: Because of its antiviral properties, amantadine may interfere with the efficacy of live attenuated influenza vaccines (LAIV). Coadministration of LAIV and amantadine is not recommended. Inactivated influenza vaccines may be used, as appropriate.

              • isavuconazonium sulfate

                isavuconazonium sulfate will increase the level or effect of amantadine by Other (see comment). Minor/Significance Unknown. Isavuconazonium sulfate, an OCT2 inhibitor, may increase the effects or levels of OCT2 substrates.

              • lisdexamfetamine

                amantadine, lisdexamfetamine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • methamphetamine

                amantadine, methamphetamine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • methylphenidate

                amantadine, methylphenidate. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • modafinil

                amantadine, modafinil. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • oxybutynin

                amantadine increases effects of oxybutynin by pharmacodynamic synergism. Minor/Significance Unknown.

              • oxybutynin topical

                amantadine increases effects of oxybutynin topical by pharmacodynamic synergism. Minor/Significance Unknown.

              • oxybutynin transdermal

                amantadine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Minor/Significance Unknown.

              • phentermine

                amantadine, phentermine. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • serdexmethylphenidate/dexmethylphenidate

                amantadine, serdexmethylphenidate/dexmethylphenidate. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Potential for additive CNS stimulation.

              • thioridazine

                amantadine increases toxicity of thioridazine by pharmacodynamic synergism. Minor/Significance Unknown. May increase Parkinsonian tremor.

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              Adverse Effects

              >10%

              Extended-release capsule (Gocovri)

              • Hallucinations (21%)
              • Dizziness (16%)
              • Dry mouth (16%)
              • Peripheral edema (16%)
              • Constipation (13%)
              • Fall (13%)
              • Orthostatic hypotension (13%)

              1-10%

              Extended-release capsule (Gocovri)

              • Urinary tract infection (10%)
              • Nausea (8%)
              • Anxiety (7%)
              • Insomnia (7%)
              • Livedo reticularis (6%)
              • Contusion (6%)
              • Depression/depressed mood (6%)
              • Headache (6%)
              • Benign prostate hyperplasia (6%)
              • Decreased appetite (6%)
              • Abnormal dreams (4%)
              • Blurred vision (4%)
              • Cough (3%)
              • Pigmentation disorder (3%)
              • Dystonia (3%)
              • Confusional state (3%)
              • Vomiting (3%)
              • Gait disturbance (3%)
              • Cataract (3%)
              • Dry eye (3%)
              • Joint swelling (3%)
              • Muscle spasms (3%)

              Immediate-release tablet/capsule or syrup

              • 5-10%
                • Nausea
                • Dizziness/lightheadedness
                • Insomnia
              • 1-5%
                • Depression
                • Anxiety and irritability
                • Hallucinations
                • Confusion
                • Anorexia
                • Dry mouth
                • Constipation
                • Ataxia
                • Livedo reticularis
                • Peripheral edema
                • Orthostatic hypotension
                • Headache
                • Somnolence
                • Nervousness
                • Dream abnormality
                • Agitation
                • Dry nose
                • Diarrhea
                • Fatigue

              <1%

              Immediate-release tablet/capsule or syrup

              • Congestive heart failure
              • Psychosis
              • Urinary retention
              • Dyspnea
              • Skin rash
              • Vomiting
              • Weakness
              • Slurred speech
              • Euphoria
              • Thinking abnormality
              • Amnesia
              • Hyperkinesia
              • Hypertension
              • Decreased libido
              • Visual disturbance
              • Corneal edema
              • Decreased visual acuity
              • Sensitivity to light
              • Optic nerve palsy
              • Convulsion
              • Leukopenia
              • Neutropenia
              • Eczematoid dermatitis
              • Suicide/ suicide ideation

              Postmarketing Reports

              Extended-release capsule (Gocovri)

              • Seizures
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              Warnings

              Contraindications

              Tablet, syrup, capsule

              • Hypersensitivity to amantadine, rimantadine
              • Untreated narrow-angle glaucoma
              • Breastfeeding

              Extended-release capsule or tablet

              • End-stage renal disease (CrCl<15 mL/min/1.73m²)

              Cautions

              Reports of falling asleep while engaged in activities of daily living (eg, operation of motor vehicles); patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event; advise patients of the potential to develop drowsiness

              Avoid abrupt withdrawal; abrupt discontinuation of amantadine may cause an increase in symptoms of Parkinson disease or cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, or slurred speech

              In clinical trials, suicidal ideation, depression, and/or depressed mood were reported; monitor for depression, including suicidal ideation or behavior

              Tablet, syrup, capsule

              • Since 2008-09 influenza season, Centers for Disease Control and Prevention (CDC) advises against use for treatment or prophylaxis of influenza in US
              • Reports of congestive heart failure (CHF), peripheral edema, and hypotension with amantadine; monitor patients with history of CHF, peripheral edema, and/or orthostatic hypotension
              • Amantadine may accumulate in the plasma and body when renal function declines; see Dosing Considerations
              • Rare instances of reversible elevation of liver enzymes have been reported in patients receiving amantadine, though the mechanism is unknown
              • History of seizures, eczematoid rash, severe psychosis or psychoneurosis
              • Consider reducing anticholinergic dosages before initiating amantadine therapy
              • Risk of neuroleptic malignant syndrome (NMS) with dosage reduction or withdrawal; management of NMS should include intensive symptomatic treatment, medical monitoring, and treatment of any concomitant serious medical problems for which specific treatments are available
              • Possibility of reduced effectiveness after several months; may regain efficacy if dosage is increased

              Extended-release capsule or tablet

              • Patients with a major psychotic disorder should ordinarily not be treated with amantadine because of the risk of exacerbating psychosis; observe patients for the occurrence of hallucinations throughout treatment, especially at initiation and after dose increases
              • In controlled clinical trials, patients experienced dizziness, syncope, orthostatic hypotension, presyncope, postural dizziness or hypotension; monitor patients for dizziness and orthostatic hypotension, especially after starting amantadine extended-release or increasing the dose

              Parkinson patients

              • Patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and inability to control these urges while taking one or more of the medications, including amantadine, that increase central dopaminergic tone
              • May be linked to higher melanoma risk; monitor for melanomas frequently and on a regular basis when using amantadine for any indication; periodic skin examinations should be performed by appropriately qualified individuals

              Drug interactions overview

              • Extended-release capsules or tablets
                • Products with anticholinergic properties may potentiate anticholinergic-like side effects of amantadine, reduce dose of anticholinergic drugs or of extended-release amantadine if atropine-like effects appear when these drugs are used concurrently
                • Since excretion rate of amantadine increases rapidly when urine is acidic, coadministration of urine acidifying drugs may increase elimination of amantadine from the body; alterations of urine pH towards the alkaline condition may lead to drug accumulation with a possible increase in adverse reactions; monitor for efficacy or adverse reactions under conditions that alter the urine pH to more acidic or alkaline, respectively
                • Because of its antiviral properties, amantadine may interfere with the efficacy of live attenuated influenza vaccines; live vaccines are not recommended during treatment; inactivated influenza vaccines may be used, as appropriate
                • Concomitant use with alcohol is not recommended, as it may potentiate central nervous system effects (eg, somnolence, dizziness, confusion, lightheadedness, and orthostatic hypotension)
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              Pregnancy & Lactation

              Pregnancy

              No adequate data on developmental risk associated with amantadine use in pregnant women; animal studies suggest a potential risk for fetal harm with amantadine; in mice and rats, adverse developmental effects (embryo lethality, increased incidence of malformations, and reduced fetal body weight) were observed when amantadine was administered to pregnant animals at clinically relevant doses

              In mice, oral administration of amantadine (0, 10, or 40 mg/kg/day) to pregnant animals during organogenesis (gestation days 7-12) resulted in embryo lethality and reduced fetal body weight at highest dose tested, which was associated with maternal toxicity; the no-effect dose for developmental toxicity in mice (10 mg/kg/day) is less than the recommended human dose (RHD) of 274 mg/day, based on body surface area (mg/m²)

              Lactation

              Amantadine is excreted into human milk, but amounts have not been quantified; there is no information on the risk to a breastfed infant; amantadine may alter breast milk production or excretion

              In published studies, amantadine reduced serum prolactin levels and symptoms of galactorrhea in patients taking neuroleptic drugs; the effect of amantadine on milk supply has not been evaluated in nursing mothers

              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.

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              Pharmacology

              Mechanism of Action

              Antiviral

              • The mechanism of antiviral activity is unknown; appears to primarily prevent the release of infectious viral nucleic acid into the host cell by interfering with transmembrane domain of viral M2 protein; amantadine is also known to prevent viral assembly during replication and inhibits replication of influenza A virus isolates from each of the subtypes (ie, H1N1, H2N2 and H3N2), but has very little or no activity against influenza B virus isolates

              Parkinson disease

              • The exact mechanism of amantadine in the treatment of Parkinson disease, drug-induced extrapyramidal reactions, dyskinesia associated with Parkinson disease is not known; amantadine is a weak, noncompetitive NMDA receptor antagonist
              • Data from early animal studies suggest that amantadine may have direct and indirect effects on dopamine neurons; amantadine may have direct and indirect effects on dopamine neurons; it exerts dopaminergic-like side effects (eg, hallucinations and dizziness) in humans; although amantadine has not been shown to possess direct anticholinergic activity, clinically, it exhibits anticholinergic-like side effects (eg, dry mouth, urinary retention, and constipation)

              Absorption

              Bioavailability: 86-90%

              Onset: Within 48 hr (antidyskinetic)

              Peak plasma time: 2-4 hr (capsule, tablets, syrup); 12 hr (extended-release capsule)

              Peak plasma concentration : 0.24 mcg/mL (100-mg single dose); 328 ng/mL (129-mg single extended-release tablet dose)

              AUC : 20-30% higher (steady-state for single ER capsule dose); 8263 ng·hr/mL (129-mg single extended-release tablet dose)

              Distribution

              Protein bound: 67%

              Vd: 1.5-6.1 L/kg (capsule, tablet, syrup); 3-8 L/kg (IV administration)

              Metabolism

              Not appreciably metabolized; small amounts of acetyl metabolite identified

              Elimination

              Half-life: 16 hr

              Clearance: 0.2-0.3 L/hr/kg (capsule, tablet, syrup); 0.27 L/hr/kg (capsule, ER)

              Excretion: Urine (80-90% unchanged) by glomerular filtration and tubular secretion

              Excretion, extended-release tablets: Urine (85% [unchanged]; 0-15% (N-acetylated compound)

              Metabolism accounts for 5-18% total clearance of amantadine

              Urine pH reported to influence excretion rate of amantadine

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              Administration

              Oral Administration

              Administer daily dose in 2 divided doses to decrease adverse CNS effects

              Administer 2nd dose several hours before bedtime to minimize insomnia

              Amantadine immediate- or extended-release products are not interchangeable

              Extended-release capsule

              Administer with or without food

              Swallow capsule whole; do not crush, chew, or divide capsules

              Missed dose: Take next dose as scheduled

              • Unable to swallow capsule
                • Administer by carefully opening and sprinkling the entire contents on small amount (teaspoonful) of soft food, such as applesauce; drug/food mixture should be swallowed immediately without chewing
                • Do not store mixture for future use

              Extended-release tablet

              • Swallow capsule whole
              • Do not chew, crush, or divide tablets; administered without regard to food
              • Missed dose: Take next dose as scheduled

              Storage

              All formulations: Store at 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F)

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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              amantadine HCl oral
              -
              100 mg capsule
              amantadine HCl oral
              -
              100 mg capsule
              amantadine HCl oral
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              100 mg capsule
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              100 mg capsule
              amantadine HCl oral
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              100 mg capsule
              amantadine HCl oral
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              100 mg tablet
              amantadine HCl oral
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              100 mg capsule
              amantadine HCl oral
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              100 mg tablet
              amantadine HCl oral
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              50 mg/5 mL solution
              amantadine HCl oral
              -
              100 mg tablet
              amantadine HCl oral
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              100 mg capsule
              amantadine HCl oral
              -
              100 mg tablet
              amantadine HCl oral
              -
              100 mg tablet
              amantadine HCl oral
              -
              50 mg/5 mL solution
              amantadine HCl oral
              -
              100 mg capsule
              amantadine HCl oral
              -
              100 mg capsule
              amantadine HCl oral
              -
              100 mg capsule
              amantadine HCl oral
              -
              50 mg/5 mL solution
              amantadine HCl oral
              -
              50 mg/5 mL solution
              Gocovri oral
              -
              137 mg capsule
              Gocovri oral
              -
              68.5 mg capsule

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

              Patient Education
              amantadine HCl oral

              AMANTADINE - ORAL

              (a-MAN-ta-deen)

              COMMON BRAND NAME(S): Symmetrel

              USES: Amantadine is used to treat Parkinson's disease, as well as side effects caused by drugs (such as drug-induced extrapyramidal symptoms), chemicals, and other medical conditions. In these cases, this medication may help to improve your range of motion and ability to exercise. For the treatment of these conditions, amantadine is believed to work by restoring the balance of natural chemicals (neurotransmitters) in the brain.Amantadine is used to prevent or treat a certain type of flu (influenza A). If you have been infected with the flu, this medication may help make your symptoms less severe and shorten the time it will take you to get better. Taking amantadine if you have been or will be exposed to the flu may help to prevent you from getting the flu. This medication is an antiviral that is believed to work by stopping growth of the flu virus. This medication is not a vaccine. To increase the chance that you will not get the flu, it is important to get a flu shot once a year at the beginning of every flu season, if possible.Based on the recommendation from the Centers for Disease Control (CDC) in the US, amantadine should not be used to treat or prevent influenza A because the current influenza A virus in the United States and Canada is resistant to this medication. For more details, talk to your doctor or pharmacist.

              HOW TO USE: Take this medication by mouth with or without food as directed by your doctor, usually once or twice daily. If you are taking this medication twice a day and have trouble sleeping after taking it, take the second dose several hours before bedtime.If you are using the liquid form of this medication, carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose.Dosage is based on your medical condition and response to therapy. In children, the dosage is also based on body weight. Do not take more than prescribed by your doctor.This medication works best when the amount of medicine in your body is kept at a constant level. Take this medication at evenly spaced intervals throughout the day and night.If you are taking amantadine for a viral infection, begin taking it as soon as possible. Continue taking it until the full prescribed amount is finished, even if symptoms disappear after a few days. Stopping the medication too early may result in a relapse of the infection.In Parkinson's disease, the effects of the medication may not be noticed for several weeks. Do not suddenly stop taking the medication because symptoms or side effects may worsen. Your doctor may want to reduce your dose gradually. This medication may not work as well after it has been taken for several months. Tell your doctor if this medication stops working well.

              SIDE EFFECTS: Blurred vision, nausea, stomach upset, drowsiness, dizziness, headache, dry mouth, constipation, nervousness, or trouble sleeping may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: purplish-red blotchy spots on the skin, swelling of the ankles/feet, difficulty urinating, vision changes, shortness of breath, mental/mood changes (such as depression, suicidal thoughts/attempts), muscle stiffness, uncontrolled muscle movements, unusual sweating, fast heartbeat, unexplained fever, unusual strong urges (such as increased gambling, increased sexual urges).Get medical help right away if you have any very serious side effects, including: seizures.Some people taking amantadine have fallen asleep suddenly during their usual daily activities (such as talking on the phone, driving). In some cases, sleep occurred without any feelings of drowsiness beforehand. This sleep effect may occur anytime during treatment with amantadine even if you have used this medication for a long time. If you experience increased sleepiness or fall asleep during the day, do not drive or take part in other possibly dangerous activities until you have discussed this effect with your doctor. Your risk of this sleep effect is increased by using alcohol or other medications that can make you drowsy. See also Precautions section.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

              PRECAUTIONS: Before taking amantadine, tell your doctor or pharmacist if you are allergic to it; or to rimantadine; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: glaucoma, swelling of arms/legs (peripheral edema), heart problems (such as heart failure), blood pressure problems (such as dizziness when standing), kidney disease, liver disease, mental/mood conditions (such as depression, psychosis), seizures, a certain skin condition (eczematoid dermatitis).This drug may make you dizzy or drowsy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis). See also Side Effects section.If you are taking this medication for Parkinson's disease, be careful not to overdo physical activity as your condition improves because this may increase your risk of falls. Consult your doctor about a plan to gradually increase your physical activity as symptoms improve.Older adults may be at a greater risk for side effects while taking this drug.During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.This drug passes into breast milk and may have undesirable effects on a nursing infant. Consult with your doctor before breast-feeding.

              DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Amantadine may interfere with the effect of certain vaccines, such as flu vaccine inhaled through the nose. However, you may get a flu shot (flu vaccine given by injection) if recommended by your doctor.

              OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include fast/irregular heartbeats, severe drowsiness, shortness of breath, change in the amount of urine, mental/mood changes (such as anxiety, aggression, confusion, hallucinations), seizures.

              NOTES: Do not share this product with others.

              MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

              STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

              Information last revised September 2022. Copyright(c) 2023 First Databank, Inc.

              IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.