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Amantadine Hydrochloride: Dosage and Administration

Administration

Amantadine hydrochloride is administered orally as a single daily dose or, preferably, in 2 equally divided doses to minimize transitory adverse effects. It has been suggested that if insomnia occurs, the last daily dose should be taken several hours before retiring.

Dosage

Adult Dosage

For symptomatic treatment or prophylaxis of uncomplicated influenza A virus illness, the usual dosage of amantadine hydrochloride for adolescents and adults younger than 65 years of age with normal renal function is 200 mg daily. This dosage can be given as a single daily dose or as 100 mg twice daily; use of 2 equally divided daily doses may minimize adverse CNS effects and therefore is preferred by some experts.

Symmetrel

The usual dosage of amantadine may need to be reduced in patients with congestive heart failure, peripheral edema, orthostatic hypotension, or impaired renal function. Some clinicians currently recommend a maximum dosage of 100 mg daily for the prophylaxis of influenza A infection because limited evidence suggests that a 100-mg daily dosage may be effective for prophylaxis in healthy adults who are not at risk for influenza-related complications and is associated with fewer adverse effects.

The relative efficacy of 100- versus 200-mg daily dosages for the treatment or prophylaxis of influenza virus A infection has not been elucidated. The 100-mg daily dosage is recommended for individuals who have CNS or other toxicities while receiving the 200-mg daily dosage.

Geriatric Dosage

Since renal function normally declines with age and amantadine-induced adverse effects have been reported more frequently in geriatric patients, the usual dosage of amantadine hydrochloride for patients 65 years of age or older without recognized renal disease is 100 mg once daily for the treatment or prophylaxis of influenza A virus infection to minimize the risk of toxicity. The CDC and other clinicians state that 100 mg daily should be the maximum dosage of amantadine hydrochloride for adults 65 years of age or older, and that dosage may need to be further reduced in some geriatric patients.

Pediatric Dosage

The dosage of amantadine hydrochloride recommended by the manufacturer for the symptomatic treatment or prophylaxis of uncomplicated influenza A virus illness in children 9-12 years of age is 100 mg twice daily. The ACIP, American Academy of Pediatrics (AAP), and other clinicians state that children 10 years of age or older who weigh 40 kg or more may receive the drug in a dosage of 200 mg daily given in 1 or 2 divided doses, but that it may be advisable to administer the drug in a dosage of 5 mg/kg daily given in 1 or 2 divided doses to those who weigh less than 40 kg, regardless of age.

While the manufacturer states that a dosage of 100 mg once daily has not been evaluated in children and there are no data demonstrating whether this dosage is as effective or safer than the 200 mg daily dosage in this age group, the AAP suggests that a dosage of 100 mg daily given in 1 or 2 divided doses is an acceptable alternative dosage for the prophylaxis of influenza A illness in children who weigh more than 20 kg.

For children 1-9 years of age, the manufacturer recommends that amantadine hydrochloride be given in a dosage of 4.4-8. mg/kg daily (up to a maximum dosage of 150 mg daily). To reduce the risk of toxicity in this age group, the ACIP, AAP, and other clinicians suggest that children 1-9 years of age receive 5 mg/kg daily given in 1 or 2 divided doses (up to a maximum dosage of 150 mg daily).

Duration of Therapy

Treatment

In the symptomatic treatment of respiratory tract illness caused by influenza A virus, amantadine hydrochloride should be administered as soon as possible, preferably within 24-48 hours after the onset of symptoms. The ACIP currently states that it may be advisable to discontinue amantadine treatment as soon as clinically warranted, generally within 3-5 days or within 24-48 hours after symptoms disappear, since there is some risk that strains of influenza A resistant to amantadine and rimantadine may emerge during treatment with the drug. However, immunocompromised individuals may require a longer course of therapy.

Prophylaxis

When a presumed influenza A outbreak occurs in a hospital, nursing home, or other institution housing high-risk patients, amantadine prophylaxis should be started as soon as possible after recognition of the outbreak and continued at least 2 weeks or until approximately 1 week after the end of the outbreak. When amantadine hydrochloride is used as an adjunct to influenza virus vaccine, the drug usually is administered for 2 weeks after the vaccine is given in order to provide chemoprophylaxis until protective antibody response develops. Children younger than 9 years of age receiving influenza virus vaccine for the first time may require amantadine prophylaxis for up to 6 weeks following vaccination or until 2 weeks after the second dose of vaccine.

When vaccination is contraindicated or otherwise not available, amantadine prophylaxis may be given throughout the period of local influenza A outbreak, which may be as long as 6-12 weeks. Amantadine prophylaxis also can be given throughout the period of outbreak when poor antibody response to influenza vaccine is expected (e.g., in patients with severe immunodeficiency, including acquired immunodeficiency syndrome [AIDS]).

The manufacturer states that prophylaxis with amantadine hydrochloride should be instituted prior to or as soon as possible after the patient has contact with an individual having a respiratory illness thought to be caused by influenza A virus, and should be continued for at least 10 days following a known exposure.

Dosage in Renal Impairment

In patients with renal impairment, amantadine hydrochloride dosage should be carefully adjusted and some clinicians recommend that blood concentrations of the drug be monitored frequently. One manufacturer recommends that patients with creatinine clearances of 15-50 mL/minute per 1.73 m receive 200 mg of amantadine on the first day, followed by 100-mg maintenance doses given once daily in patients with creatinine clearances of 30-50 mL/minute per 1.73 m or once every other day in those with creatinine clearances of 15-29 mL/minute per 1.73 m. This manufacturer recommends that patients with creatinine clearances less than 15 mL/minute per 1.73 m and hemodialysis patients receive 200 mg of amantadine every 7 days.

Because dosage adjustment based on creatinine clearance may provide only an approximation of the optimal dosage for a given patient, such patients should be observed carefully so that adverse reactions can be recognized promptly and either the dose can be reduced further or the drug can be discontinued as necessary. Hemodialysis contributes minimally to clearance of amantadine.

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