Today's med: Amantadine (brand name: Symmetrel)
Index terms: Amantadine HCL, Adamantanamine Hydrochloride)
Drug Class: Anti-Parkinson's Agent, Dopamine Agonist, Antiviral Agent
Other Drugs in this class:
Action: As an antiviral, blocks the uncoating of influenza A virus preventing penetration of virus into host; antiparkinsonian activity may be due to its blocking the reuptake of dopamine into presynaptic neurons or by increasing dopamine release from presynaptic fibers.
Indications:
Contraindications: Hypersensitivity to amantadine or any component of the formulation
Adverse Effects: Most common: Patient may experience presyncope, fatigue, blurred vision, illogical thinking, nausea, or insomnia. Have patient report immediately to prescriber significant change in balance, or rash. Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat).
1% to 10%: Cardiovascular: Orthostatic hypotension, peripheral edema
Central nervous system: Agitation, anxiety, ataxia, confusion, delirium, depression, dizziness, dream abnormality, fatigue, hallucinations, headache, insomnia, irritability, lightheadedness, nervousness, somnolence
Dermatologic: Livedo reticularis
Gastrointestinal: Anorexia, constipation, diarrhea, nausea, xerostomia
Respiratory: Dry nose
<1% (Limited to important or life-threatening): Aggressive behavior, agranulocytosis, alkaline phosphatase increased, allergic reaction, ALT increased, AST increased, amnesia, anaphylaxis, arrhythmia, bilirubin increased, BUN increased, cardiac arrest, coma, CPK increased, creatinine increased, delusions, diaphoresis, dysphagia, dyspnea, eczematoid dermatitis, euphoria, GGT increased, heart failure, hyperkinesis, LDH increased, leukopenia, mania, neutropenia, neuroleptic malignant syndrome (NMS; associated with dosage reduction or abrupt withdrawal of amantadine), oculogyric episodes, paresthesia, photosensitivity, psychosis, pulmonary edema, rash, respiratory failure (acute), seizures, suicidal ideation, suicide, urinary retention, withdrawal reactions (may include delirium, hallucinations, and psychosis), visual disturbances
Reported with dopamine agonists: Impulsive/compulsive behaviors (eg, pathological gambling, hypersexuality, binge eating)
Concerns related to adverse effects:
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• Impulse control disorders: Dopamine agonists used for Parkinson’s disease or restless legs syndrome have been associated with compulsive behaviors and/or loss of impulse control, which has manifested as pathological gambling, libido increases (hypersexuality), and/or binge eating. Causality has not been established, and controversy exists as to whether this phenomenon is related to the underlying disease, prior behaviors/addictions and/or drug therapy. Dose reduction or discontinuation of therapy has been reported to reverse these behaviors in some, but not all cases.
• Melanoma: Risk for melanoma development is increased in Parkinson’s disease patients; drug causation or factors contributing to risk have not been established. Patients should be monitored closely and periodic skin examinations should be performed.
• Neuroleptic malignant syndrome: Has been associated with neuroleptic malignant syndrome (associated with dose reduction or abrupt discontinuation).
• Suicidal ideation: There have been reports of suicidal ideation/attempt in patients with and without a history of psychiatric illness. May exacerbate mental problems in patients with a history of mental illness.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with heart failure, peripheral edema, or orthostatic hypotension; dosage reduction may be required.
• Eczema: Use with caution in patients with a history of recurrent and eczematoid dermatitis.
• Glaucoma: Avoid in untreated angle closure glaucoma.
• Hepatic impairment: Use with caution in patients with hepatic impairment; rarely, elevations in transaminases have been reported.
• Influenza A: Appropriate use: Consult current guidelines. Due to increased resistance, the ACIP has recommended that rimantadine and amantadine no longer be used for the treatment or prophylaxis of influenza A in the United States until susceptibility has been re-established.
• Parkinson's disease: Appropriate use: When treating Parkinson's disease, do not discontinue abruptly. In many patients, the therapeutic benefits of amantadine are limited to a few months.
• Psychosis: Use with caution in patients with uncontrolled psychosis or severe psychoneurosis.
• Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended.
• Seizure disorder: Use with caution in patients with a history of seizure disorder.
Concurrent drug therapy issues:
• CNS stimulants: Use with caution in patients receiving CNS stimulant drugs.
Special populations:
• Elderly: Use with caution in the elderly; may be more susceptible to CNS effects (using 2 divided daily doses may minimize this effect). These patients may require dosage reductions based on renal function.
• Pediatrics: Safety and efficacy have not been established in children <1 year of age.
Pregnancy Risk Factor C; Influenza infection may be more severe in pregnant women. Untreated influenza infection is associated with an increased risk of adverse events to the fetus and an increased risk of complications or death to the mother. Oseltamivir and zanamivir are currently recommended for the treatment or prophylaxis influenza in pregnant women and women up to 2 weeks postpartum. Antiviral agents are currently recommended as an adjunct to vaccination and should not be used as a substitute for vaccination in pregnant women (consult current CDC guidelines).
Other warnings/precautions:
• Withdrawal syndrome: May cause agitation, anxiety, delirium, delusions, depression, hallucinations, paranoia, parkinsonian crisis, slurred speech, or stupor. Upon discontinuation of amantadine therapy, gradually taper dose.
Standard Dosing:
Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations.
Influenza A treatment:
1-9 years: 5 mg/kg/day in 2 divided doses (manufacturers range: 4.4-8.8 mg/kg/day); maximum dose: 150 mg/day
≥10 years and <40 kg: 5 mg/kg/day in 2 divided doses (CDC, 2011)
≥10 years and ≥40 kg: 100 mg twice daily (CDC, 2011)
Note: Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days)
Influenza A prophylaxis: Refer to “Influenza A treatment” dosing. Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed. For children <9 years receiving influenza vaccine for the first time, amantadine prophylaxis should continue for 6 weeks (4 weeks after the first dose and 2 weeks after the second dose).
Adults: Drug-induced extrapyramidal symptoms: 100 mg twice daily; may increase to 300 mg/day in divided doses, if needed
Parkinson's disease: Usual dose: 100 mg twice daily as monotherapy; may increase to 400 mg/day in divided doses, if needed, with close monitoring. Note: Patients with a serious concomitant illness or those receiving high doses of other anti-parkinson drugs should be started at 100 mg/day; may increase to 100 mg twice daily, if needed, after one to several weeks.
Influenza A treatment/prophylaxis: Note: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Please refer to the current ACIP recommendations. The following is based on the manufacturer’s labeling:
Influenza A treatment: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects); Note:Initiate within 24-48 hours after onset of symptoms; continue for 24-48 hours after symptom resolution (duration of therapy is generally 3-5 days).
Influenza A prophylaxis: 200 mg once daily or 100 mg twice daily (may be preferred to reduce CNS effects).Note: Continue prophylaxis throughout the peak influenza activity in the community or throughout the entire influenza season in patients who cannot be vaccinated. Development of immunity following vaccination takes ~2 weeks; amantadine therapy should be considered for high-risk patients from the time of vaccination until immunity has developed.
Elderly (≥65 years): Adjust dose based on renal function; some patients tolerate the drug better when it is given in 2 divided daily doses (to avoid adverse neurologic reactions).
Influenza A treatment/prophylaxis: 100 mg once daily
Lab interference: May interfere with urine detection of amphetamines/methamphetamines (false-positive).
Drug
interactions: Link: http://www.drugs.com/drug-interactions/amantadine.html
A total of 418 drugs (2754 brand and generic names) are known to interact with amantadine.
- 6 major drug interactions (50 brand and generic names)
- 350 moderate drug interactions (2490 brand and generic names)
- 62 minor drug interactions (214 brand and generic names)
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