amantadine (Rx)

Brand and Other Names:Osmolex ER, Gocovri
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

capsule or tablet (generic)

  • 100mg

syrup (generic)

  • 50mg/5mL

capsule, extended-release (Gocovri)

  • 68.5mg
  • 137mg

tablet, extended-release (Osmolex ER)

  • 129mg
  • 193mg
  • 258mg
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Parkinson Disease

Tablet/syrup/capsule

  • Monotherapy: 100 mg/day PO initially; may be increased to 100 mg q12hr after at least 1 week; dose may increase up to 400 mg/day in divided doses with close monitory if necessary
  • 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/day PO qDay initially in the morning; may increase dose in weekly intervals, not to exceed 322 mg/day taken in the morning
  • For patients unable to tolerate >100 mg/day of immediate-release amantadine, there is no equivalent dose or dosing regimen of extended-release tablets

Dyskinesia Associated with Parkinson Disease

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

Extended-release capsule (Gocovri): 137 mg PO once qHS; increase to recommended dose of 274 mg (two 137 mg extended-release capsules) PO qHS after 1 week

See Administration

Drug-Induced Extrapyramidal Symptoms

Tablet/syrup/capsule

  • Indicated in the treatment of drug-induced extrapyramidal reactions
  • 100 mg PO q12hr; not to exceed 300 mg/day

Extended-release tablet (Osmolex ER)

  • Indicated in the treatment of drug-induced extrapyramidal reactions
  • 129 mg/day PO qDay initially in the morning; may increase dose in weekly intervals, not to exceed 322 mg/day taken in the morning
  • 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

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

200 mg; two 100 mg tablets (or 4 teaspoonfuls of syrup) as a single daily dose; may split daily dosage to one 100 mg tablet (or 2 teaspoonfuls of syrup) q12hr; if central nervous system effects develop in once-a-day dosage, a split dosage schedule may reduce such complaints

Dosage Modifications

Renal impairment

  • Capsule, tablet, 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; hemodialysis: 200 mg PO weekly
  • Extended-release capsule (Gocovri)
    • CrCl 30-59 mL/min: 68.5 mg PO qHS initially; not to exceed 137 mg PO qHS
    • CrCl 15-29 mL/min: 68.5 mg PO qHS
    • CrCl <15 mL/min: Contraindicated
    • Hemodialysis: Inefficiently removed
  • Extended-release tablet (Osmolex ER)
    • There are 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 59 mL/min/1.73 m²): May increase q4Weeks; take 1 dose q96hr
    • End-stage renal disease (CrCl<15 59 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

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 (generic)

  • 100mg

syrup (generic)

  • 50mg/5mL
more...

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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    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

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            Adverse Effects

            >10%

            Extended-release capsule

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

            1-10% (tablet, syrup, capsule)

            5-10%

            • Nausea
            • Dizziness/ lightheadedness
            • Insomnia

            1-5%

            • Agitation, irritability
            • Anorexia
            • Anxiety, hallucinations, insomnia, depression, confusion, dream abnormality
            • Ataxia
            • Confusion
            • Constipation, diarrhea, xerostomia
            • Depression
            • Diarrhea
            • Dizziness, headache
            • Dry mouth
            • Dry nose
            • Fatigue, somnolence
            • Livedo reticularis
            • Nervousness
            • Orthostatic hypotension, peripheral edema

            1-10% (extended-release capsule)

            Urinary tract infection (10%)

            Anxiety (7%)

            Insomnia (7%)

            Depression/depressed mood (6%)

            Contusion (6%)

            Livedo reticularis (6%)

            Decreased appetite (6%)

            Benign prostatic hyperplasia (6%)

            Blurred vision (4%)

            Abnormal dreams (4%)

            Confusional state (3%)

            Vomiting (3%)

            Dystonia (3%)

            Pigmentation disorder (3%)

            Cataract (3%)

            <1% (tablet, syrup, capsule)

            0.1-1%

            • Amnesia, slurred speech, thinking abnormality
            • Congestive heart failure
            • Corneal edema
            • Decreased visual acuity, sensitivity to light
            • Decreased libido
            • Dyspnea
            • Eczematoid dermatitis
            • Euphoria
            • Hyperkinesis
            • Hypertension, urinary retention
            • Instances of convulsions, psychosis
            • Leukopenia
            • Neutropenia
            • Oculogyric episodes (punctate subepithelial or other corneal opacity, optic nerve palsy), visual disturbances
            • Rash

            <0.1%

            • Convulsion
            • Leukopenia
            • Neutropenia
            • Eczematoid dermatitis
            • Oculogyric episodes
            • Suicidal attempt
            • Suicide
            • Suicidal ideation
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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

            Extended-release capsule

            • Swallow capsule whole; do not crush, chew, or divide capsules
            • Administered by carefully opening and sprinkling the entire contents on a 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
            • Administer with or without food

            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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            Formulary

            FormularyPatient Discounts

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            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.
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            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
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            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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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.