Dosage and Administration
Creatinine Clearance
(mL/min/1.73m2) | Dosage Adjustment | | 30–50 | 200 mg on day 1, then 100 mg/day | | 15–29 | 200 mg on day 1, then 100 mg on alternate days | | <15 | 200 mg every 7 days |
Usual dose for all indications is 100 mg/day in divided doses. Further adjust dose based on renal function. See Table 5. Due to the high incidence of resistance, consult current guidelines and recommendations prior to the use of amantadine for prophylaxis or treatment of influenza A. The usual dosage of amantadine may need to be reduced in patients with heart failure, peripheral edema, orthostatic hypotension or impaired renal function.
If insomnia occurs after amantadine administration, the last daily dose should be taken several hours before bedtime.
There are no known interactions between amantadine and food. Prophylaxis and Treatment: 200 mg every 7 days.
| Indication | Age/Weight | Usual Dose | Maximum Dose | Clinical Comment | | Influenza A (treatment) | 1–9 years | 5 mg/kg/day | 150 mg/day | In 2 divided doses. Initiate within 24–48 hours after onset of symptoms; continue for 24–48 hours after symptoms disappear or up to 5 days. | | ≥10 years and <40 kg | 5 mg/kg/day | 200 mg/day | | ≥10 years and ≥40 kg | Refer to adult dosing | 200 mg/day | | Influenza A (prophylaxis) | 1–9 years | 5 mg/kg/day | 150 mg/day | Continue for at least 10 days following a known exposure.
Prophylaxis may be discontinued 2 weeks after vaccination. For children <9 years old who are vaccinated for the first time, continue prophylaxis until 2 weeks after the 2nd dose.
For patients who cannot be vaccinated, continue prophylaxis for the duration of influenza activity in the community. | | ≥10 years and <40 kg | 5 mg/kg/day | 200 mg/day | | ≥10 years and ≥40 kg | Refer to adult dosing | 200 mg/day |
| Indication | Usual Dose | Clinical Comment | | Influenza A (treatment) | 100 mg po twice daily or 200 mg po once daily | Initiate within 24–48 hours after onset of symptoms; continue for 24–48 hours after symptoms disappear or up to 5 days. | | Influenza A (prophylaxis) | 100 mg po twice daily or 200 mg po once daily | Continue for at least 10 days following a known exposure.
Prophylaxis may be discontinued 2 weeks after vaccination.
For patients who cannot be vaccinated, continue prophylaxis for the duration of influenza activity in the community. | | Parkinsonism (monotherapy) | 100 mg po twice daily | May initiate at 100 mg daily and increase after 1–2 weeks to minimize side effects. Maximum: 400 mg/day in divided doses. | | Drug-induced extrapyramidal effects | 100 mg po twice daily | Maximum dose of 300 mg/day in divided doses. |
Adverse Reactionselevation of blood urea nitrogen, creatinine. elevations of alkaline phosphatase, ALT, AST and bilirubin. Allergic reactions including anaphylaxis, pruritus, eczematoid dermatitis, skin rash, photosensitization and diaphoresis have occurred rarely. Urinary retention, which can be an early sign of toxicity. amnesia, euphoria, hyperkinesia, psychosis, seizures, slurred speech, suicidal ideation, suicide, abnormal thinking, weakness, aggressive behaviour, paresthesia, impulsive/compulsive behaviour. dyspnea, pulmonary edema, respiratory failure. visual disturbance including punctate subepithelial or other corneal opacity, corneal edema, decreased visual acuity, sensitivity to light and optic nerve palsy; oculogyric episodes, mydriasis.
| Body System | Effect | Approximate Incidence (%) | | CNS | Dizziness | 5–10 | | Insomnia | 5–10 | | Agitation | 1–5 | | Anxiety and irritability | 1–5 | | Ataxia | 1–5 | | Confusion | 1–5 | | Delirium | 1–5 | | Depression | 1–5 | | Dream abnormality | 1–5 | | Hallucinations | 1–5 | | Headache | 1–5 | | Nervousness | 1–5 | | Somnolence | 1–5 | | Gastrointestinal | Nausea | 5–10 | | Anorexia | 1–5 | | Constipation | 1–5 | | Diarrhea | 1–5 | | Xerostomia | 1–5 | | Dermatologic | Livedo reticularis | 1–5 | | Cardiovascular | Orthostatic hypotension | 1–5 | | Peripheral edema | 1–5 | | Respiratory | Dry nose | 1–5 |
heart failure, hypertension
Indications and Clinical UseAmantadine is indicated for the prevention and treatment of influenza A infections. Due to a high incidence of resistance, current guidelines and recommendations should be consulted to determine susceptibility prior to the use of amantadine. Immunization with trivalent inactivated influenza vaccine remains the primary tool for the prevention of influenza infection and illness.
Amantadine is indicated for the treatment of early stage Parkinson’s disease as monotherapy.
Amantadine is indicated for the treatment of drug-induced extrapyramidal symptoms, including levodopa-induced dyskinesia. OverdosageThere is no specific antidote for amantadine overdosage. General supportive measures should be instituted and cardiovascular status (ECG/telemetry), blood pressure, pulse, respiration, temperature, serum electrolytes, urinary output and urine pH should be monitored. Acute toxic psychosis (disorientation, confusion, visual hallucinations and aggressive behaviour), urinary retention/renal failure, a mixed acid-base disturbance, seizures, arrhythmia (e.g., QT prolongation and torsades de pointes), cardiac arrest and death. Death has been in reported in doses as low as 1 g.
Warnings and PrecautionsCareful attention is required when used in the elderly as they may be more susceptible to CNS effects. Dosage adjustment may be necessary (see Dosage and Administration). Dosage adjustment in renal impairment is recommended (see Dosage and Administration). Use with caution in patients with liver disease. Use with caution in patients with history of epilepsy or other seizures. Monitor patients for increased seizure activity. Avoid simultaneous use of amantadine for prophylaxis and treatment of amantadine-sensitive influenza A within a health care facility as this may increase the development of amantadine resistance. Safety and efficacy of amantadine in neonates and infants less than 1 year old have not been established. Patients should be cautioned about performing tasks which require mental alertness, such as driving or operating heavy machinery, as amantadine can cause decreased alertness and blurred vision. The prevalence of amantadine resistance among strains of influenza A virus varies on a yearly basis depending on the season’s circulating strains. Resistance seems to result from alterations in the transmembrane domain of the viral M2 protein, and can occur spontaneously or emerge rapidly within 2-3 days of initiating therapy. Susceptibility testing is conducted by the National Microbiology Laboratory each year, and current guidelines and recommendations should be consulted prior to the use of amantadine [www.phac-aspc.gc.ca/naci-ccni/index-eng.php]. Increased risk of mydriasis; should not be used in patients with angle-closure glaucoma. Eczematoid rash has been reported and is more likely in those with a history of the condition. Use with caution in patients with recurrent eczematoid dermatitis. There are no adequate and well controlled studies on the effects of amantadine in pregnancy. Although a small number of birth defects have been reported in women using amantadine during the first trimester, a causal relationship has not been established. No specific data is available, but it is expected that amantadine would pass to the placenta based on its small molecular size. Amantadine should be used only when the potential benefits outweigh the possible risks to the fetus. Amantadine is excreted into breast milk. Use is not recommended in nursing mothers. Patients with a history of heart failure or peripheral edema should be followed closely as heart failure has been reported in patients receiving amantadine. Use with caution in patients with a history of psychiatric disorders as symptoms may be exacerbated.
Storage and StabilityStore at controlled room temperature (15 to 30°C) in a tightly closed container. Action and Clinical PharmacologyThe elimination half-life in elderly males is prolonged and ranges from 20 to 41 hours. The volume of distribution of amantadine ranges from 3 to 8 L/kg. Amantadine is distributed into tissues and fluids including saliva, tear film and nasal secretions and crosses the blood brain barrier. Amantadine is 67% protein bound. Amantadine is well absorbed after oral administration. Peak serum concentrations occur within about 2 to 4 hours after administration. Amantadine acts as an antiviral by inhibiting viral uncoating through interference of M2 ion-channel function. In certain influenza strains, the irreversible conversion of hemagglutinin and subsequent prevention of virus release may also contribute to antiviral effects. Amantadine has no appreciable activity against Influenza B virus. The exact mechanism of amantadine in the treatment of parkinsonian syndrome and drug-induced extrapyramidal reactions is not known. Amantadine is a non-competitive N-methyl-D-Aspartic acid (NMDA) receptor antagonist. There is some evidence that amantadine may exert its antiparkinsonian activity through inhibition of the NMDA receptor as well as by augmenting the release of dopamine from nerve terminals and delaying dopamine re-uptake. Principally, amantadine is excreted unchanged in the urine (80-90%). The elimination half-life ranges from 10 to 25 hours. In patients with renal insufficiency (creatinine clearance less than 40 mL/min/ 1.73 m2), the elimination half-life is prolonged by two- to three-fold or greater. Amantadine is minimally removed by hemodialysis. The average elimination half life in patients on chronic maintenance hemodialysis is 8 days. The metabolism of amantadine is minimal though small amounts of N-acetylated metabolites may be identified.
ContraindicationsPatients who are hypersensitive to amantadine hydrochloride or to any ingredient in the formulation or component of the container.
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