Amantadine Dosage

Usual Adult Dose for Influenza

On the basis of available antiviral testing results, the US Public Health Service Centers for Disease Control and Prevention (CDC) has provided an interim recommendation that amantadine not be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2010 through 2011 influenza season. (During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of influenza.)

Normally recommended dose: 200 mg/day orally in 1 to 2 divided doses

For prophylaxis, 100 mg daily is an acceptable alternative in healthy adults who are not at risk for influenza-related complications. It is recommended for patients who cannot tolerate the 200 mg daily dosage because of central nervous system and other toxicities.

Usual Adult Dose for Influenza Prophylaxis

On the basis of available antiviral testing results, the US Public Health Service Centers for Disease Control and Prevention (CDC) has provided an interim recommendation that amantadine not be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2010 through 2011 influenza season. (During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of influenza.)

Normally recommended dose: 200 mg/day orally in 1 to 2 divided doses

For prophylaxis, 100 mg daily is an acceptable alternative in healthy adults who are not at risk for influenza-related complications. It is recommended for patients who cannot tolerate the 200 mg daily dosage because of central nervous system and other toxicities.

Usual Adult Dose for Parkinson's Disease

100 mg orally twice a day when used alone or 100 mg once daily in patients with serious associated medical illnesses or receiving high dosages of other antiparkinson medications

After a minimum of one week, the dosage may be increased as needed and as tolerated. Some patients may require and tolerate 300 to 400 mg/day, in divided doses, with close supervision.

Amantadine's effectiveness can wane over time, in some cases after just a few months of use. If the patient is not already at the maximum tolerated dosage at that point, increasing the dosage may help. Alternatively, a temporary discontinuation of the drug for several weeks may help to recover some of the drug's effects when it is reinstated. The use of other antiparkinson drugs may be necessary.

If amantadine is initiated concurrently with levodopa, the dosage of amantadine should remain constant at the starting level while the dosage of levodopa is titrated to achieve optimal therapeutic response.

Usual Adult Dose for Extrapyramidal Reaction

100 mg orally twice a day

After a minimum of one week, the dosage may be increased as needed and as tolerated. Some patients may require and tolerate 300 to 400 mg/day, in divided doses, with close supervision.

Usual Geriatric Dose for Influenza

On the basis of available antiviral testing results, the CDC has provided an interim recommendation that amantadine not be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2010 through 2011 influenza season. (During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of influenza.)

Normally recommended dose: 100 mg/day orally in 1 to 2 divided doses

Usual Geriatric Dose for Influenza Prophylaxis

On the basis of available antiviral testing results, the CDC has provided an interim recommendation that amantadine not be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2010 through 2011 influenza season. (During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of influenza.)

Normally recommended dose: 100 mg/day orally in 1 to 2 divided doses

Usual Pediatric Dose for Influenza

On the basis of available antiviral testing results, the CDC has provided an interim recommendation that amantadine not be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2010 through 2011 influenza season. (During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of influenza.)

Normally recommended doses:
1 to 9 years: 4.4 to 8.8 mg/kg orally per day, not to exceed 150 mg/day
10 to 12 years: 200 mg/day orally in 1 to 2 divided doses

To reduce the risk of toxicity, the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) recommend that children 1 to 9 years of age receive 5 mg/kg/day (up to 150 mg/day). Children 10 years of age or older weighing less than 40 kg should also receive 5 mg/kg/day, while those weighing 40 kg or more may receive 200 mg/day. For prophylaxis, 100 mg daily is an acceptable alternative in children weighing more than 20 kg who are not at risk for influenza-related complications.

Usual Pediatric Dose for Influenza Prophylaxis

On the basis of available antiviral testing results, the CDC has provided an interim recommendation that amantadine not be used for the treatment or prophylaxis of influenza A in the United States for the remainder of the 2010 through 2011 influenza season. (During this period, oseltamivir or zanamivir should be selected if an antiviral medication is used for the treatment and prophylaxis of influenza.)

Normally recommended doses:
1 to 9 years: 4.4 to 8.8 mg/kg orally per day, not to exceed 150 mg/day
10 to 12 years: 200 mg/day orally in 1 to 2 divided doses

To reduce the risk of toxicity, the Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) recommend that children 1 to 9 years of age receive 5 mg/kg/day (up to 150 mg/day). Children 10 years of age or older weighing less than 40 kg should also receive 5 mg/kg/day, while those weighing 40 kg or more may receive 200 mg/day. For prophylaxis, 100 mg daily is an acceptable alternative in children weighing more than 20 kg who are not at risk for influenza-related complications.

Renal Dose Adjustments

CrCl 30 to 50 mL/min: 200 mg orally the first day and 100 mg each day thereafter
CrCl 15 to 29 mL/min: 200 mg orally the first day and 100 mg every other day thereafter
CrCl 14 mL/min or less: 200 mg orally every 7 days

Liver Dose Adjustments

Caution is recommended in patients with liver disease. Reversible liver enzyme elevations have been reported.

Dose Adjustments

The dosage may require careful adjustment in patients with congestive heart failure, peripheral edema, or orthostatic hypotension, since amantadine may exacerbate these conditions.

High dosages (e.g., 300 to 400 mg/day) should generally be avoided in patients over the age of 65, even when renal function is adequate, since older patients tend to be more sensitive to the adverse effects of amantadine.

Precautions

Amantadine overdose may cause cardiac, respiratory, and central nervous system toxicity. Fatalities have resulted from doses as low as 1 g.

Amantadine may precipitate or exacerbate psychotic symptoms. Rarely, suicide attempts and suicidal ideation have also been reported, some of which occurred in patients with no prior history of psychiatric illness who were taking short courses of amantadine for influenza. Therapy with amantadine should be administered cautiously in patients with a history of psychiatric disorders, emotional instability, or substance abuse, and particularly if they are elderly. It may be prudent to refrain from dispensing large quantities of amantadine to these patients to prevent intentional overdose, which is potentially fatal.

Amantadine may rarely precipitate or exacerbate seizure activity. Patients with epilepsy or a predisposition for seizures should be monitored closely for increased seizure activity during therapy with amantadine.

Amantadine may infrequently cause edema, orthostatic hypotension and, rarely, congestive heart failure. Patients with these conditions should be monitored closely for increased or worsening symptoms. Dosage adjustments may be necessary.

Because of its anticholinergic and possible mydriatic effects, amantadine should not be used in patients with untreated angle closure glaucoma.

Dose adjustments of amantadine or other concomitant anticholinergic drugs may be required if atropine-like effects occur.

Amantadine therapy should not be stopped abruptly in patients with Parkinson's disease, since sudden withdrawal may result in a parkinsonian crisis. Abrupt discontinuation may also cause delirium, agitation, delusions, hallucinations, paranoid reaction, stupor, anxiety, depression, and slurred speech.

Sporadic cases of possible neuroleptic malignant syndrome (NMS) have been associated with dosage reduction or withdrawal of amantadine therapy. Clinical manifestations of NMS include hyperpyrexia, muscle rigidity, involuntary movements, altered mental status, and autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias). Laboratory findings may include creatine phosphokinase elevation, leukocytosis, and increased serum myoglobin. Clinicians treating patients with amantadine should be aware of the possibility for development of this uncommon but life-threatening syndrome so as to ensure prompt recognition, diagnosis and treatment when necessary.

Studies have indicated that patients with Parkinson's disease have an elevated risk of developing melanoma compared to the general population. Whether the higher risk was due to Parkinson's disease or other factors (such as drugs to treat Parkinson's disease) has not been established. Frequent and regular monitoring for melanomas is recommended when using amantadine for any indication. Preferably, qualified health care providers (e.g., dermatologists) should perform periodic skin examinations.

Intense urges to gamble, increased sexual urges, and other intense urges, and the inability to control these urges have been reported during treatment with 1 or more drugs that increase central dopaminergic tone and are generally used for Parkinson's disease, including amantadine. Patients should be asked about the development of new or increased gambling urges, sexual urges, or other urges and should inform their physician if they experience these urges. Dose reduction or drug discontinuation should be considered if a patient develops such urges during amantadine therapy.

Influenza viruses change over time and the emergence of resistant or more virulent mutations may decrease the efficacy of amantadine. The available influenza drug susceptibility patterns and treatment effects should be considered when deciding whether to use amantadine.

Dialysis

Amantadine is not significantly removed by hemodialysis, thus supplementary dosing is not required following hemodialysis. The recommended dosage for patients on hemodialysis is 200 mg every 7 days.

Other Comments

Influenza treatment: Amantadine should be started within 48 hours after onset of symptoms and discontinued as soon as clinically warranted, generally after 3 to 5 days of treatment or within 24 to 48 hours after symptoms disappear. Patients should be informed that treatment with amantadine has not been shown to reduce the risk of transmission of influenza to others and to avoid contact with uninfected persons as much as possible.

Influenza prophylaxis: Amantadine should be started in anticipation of an outbreak and before or after a known exposure. For maximal effectiveness in an outbreak, the drug should be continued for the entire duration of influenza activity in the community, or at least during the period of peak influenza activity if cost is a concern. When used as an adjunct to influenza vaccination, amantadine may be given for approximately 2 weeks to provide interim protection until development of adequate antibody response. Children receiving influenza virus vaccine for the first time may require amantadine prophylaxis for up to 6 weeks following vaccination or 2 weeks after the second dose of vaccine. Prophylaxis given before or after contact with individuals who have influenza A respiratory tract illness should be continued for at least 10 days following exposure.

Influenza-like illnesses are caused by many different viruses. The activity of amantadine is limited to influenza A.

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