Usage
Amantadine is prescribed for the treatment of Parkinson’s disease, drug-induced extrapyramidal reactions, and influenza A viral infections. Its pharmacological classifications include antiviral, antiparkinsonian, and antidyskinetic. Amantadine’s mechanism of action involves increasing dopamine release, blocking dopamine reuptake, and as an NMDA receptor antagonist. It is important to note that due to widespread resistance, amantadine is no longer recommended for influenza A treatment or prophylaxis.
Alternate Names
Amantadine hydrochloride is the chemical name, often shortened to amantadine. Brand names include Symmetrel, Gocovri (extended-release capsules), and Osmolex ER (extended-release tablets).
How It Works
Pharmacodynamics: Amantadine primarily exerts its antiparkinsonian effects by increasing dopamine release and inhibiting its reuptake in the striatum. This leads to higher dopamine levels, mitigating the dopamine deficiency characteristic of Parkinson’s disease. Additionally, amantadine acts as an NMDA receptor antagonist, possibly contributing to its efficacy against dyskinesias. As an antiviral, amantadine targets the M2 protein of influenza A, inhibiting viral uncoating.
Pharmacokinetics: Amantadine is well-absorbed orally. It undergoes minimal metabolism and is primarily excreted unchanged by the kidneys. Its half-life is prolonged in patients with renal impairment. The extended-release formulations of amantadine, Gocovri and Osmolex ER, provide a more gradual release of the drug, extending its duration of action.
Dosage
Standard Dosage
Adults:
- Parkinson’s Disease (Immediate Release): 100 mg orally twice daily. May increase to 200 mg twice daily after one week if tolerated and needed. Maximum dose is generally 300 mg/day, but some patients may tolerate up to 400 mg/day in divided doses. For patients with serious concomitant illnesses or taking other antiparkinsonian medications, start with 100 mg once daily.
- Parkinson’s Disease (Gocovri): 137 mg orally once daily at bedtime initially; increase to 274 mg (two 137 mg capsules) once daily at bedtime after one week.
- Parkinson’s Disease (Osmolex ER): 129 mg orally once daily in the morning initially. May increase dose weekly, not to exceed 322 mg/day (one 129 mg and one 193 mg tablet).
- Drug-Induced Extrapyramidal Reactions: Similar to Parkinson’s disease dosing.
- Influenza A (No longer recommended due to resistance): Previously, 200 mg orally once daily or 100 mg twice daily.
Children:
- Influenza A (No longer recommended due to resistance): Previously, for children 1-9 years, 4.4 to 8.8 mg/kg/day orally divided into two doses, not to exceed 150 mg/day. For children 9-12 years, 100 mg twice daily.
- Parkinson’s disease: Dosage must be determined by the doctor.
- Other Indications: Consult a doctor for appropriate dosing.
Special Cases:
- Elderly Patients: Initiate at a lower dose (e.g., 100 mg/day) and titrate cautiously due to age-related decline in renal function. A maximum daily dose of 100 mg may be sufficient for some elderly patients.
- Patients with Renal Impairment: Dose adjustments are crucial. See detailed guidelines below in Dosage Adjustments section for creatinine clearance based adjustments.
- Patients with Hepatic Dysfunction: No specific dosage adjustments are typically required, but caution is advised.
- Patients with Comorbid Conditions: Careful monitoring is essential. Consider lower initial doses and slower titration in patients with cardiovascular disease, epilepsy, psychiatric disorders, or other relevant conditions.
Clinical Use Cases
Amantadine is not typically indicated for specific medical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Renal Impairment (Immediate Release):
- CrCl 30-50 mL/min: 200 mg on day 1, then 100 mg daily.
- CrCl 15-29 mL/min: 200 mg on day 1, then 100 mg every other day.
- CrCl <15 mL/min: 200 mg every 7 days.
- Renal Impairment (Gocovri):
- Mild (CrCl 60-89 mL/min/1.73 m²): No adjustment needed.
- Moderate (CrCl 30-59 mL/min/1.73 m²): 68.5 mg at bedtime initially; may increase to 137 mg at bedtime after 1 week.
- Severe (CrCl 15-29 mL/min/1.73 m²): 68.5 mg at bedtime.
- End-stage renal disease (CrCl <15 mL/min/1.73 m²): Contraindicated.
- Renal Impairment (Osmolex ER):
- Mild (CrCl 60-89 mL/min/1.73 m²): Increase dose weekly; take once daily.
- Moderate (CrCl 30-59 mL/min/1.73 m²): Increase every 3 weeks; take every 48 hours.
- Severe (CrCl 15-29 mL/min/1.73 m²): Increase every 4 weeks; take every 96 hours.
- End-stage renal disease (CrCl <15 mL/min/1.73 m²): Contraindicated.
Side Effects
Common Side Effects:
Nausea, dizziness, lightheadedness, insomnia, dry mouth, constipation, peripheral edema, livedo reticularis (lace-like purplish skin discoloration), and anxiety.
Rare but Serious Side Effects:
Neuroleptic malignant syndrome (NMS), psychosis, suicidal ideation, depression, hallucinations, seizures, heart failure, and orthostatic hypotension.
Long-Term Effects:
Chronic complications from prolonged use are rare but can include worsening of pre-existing psychiatric conditions and the development of impulse control disorders (e.g., compulsive gambling, hypersexuality).
Adverse Drug Reactions (ADR):
NMS, severe psychosis, suicidal behavior, severe orthostatic hypotension, and serious cardiac arrhythmias.
Contraindications
Absolute contraindications include hypersensitivity to amantadine and end-stage renal disease (for extended-release formulations). Relative contraindications include a history of seizures, psychosis, heart failure, and severe liver disease. Caution is advised in patients with glaucoma or prostatic hypertrophy.
Drug Interactions
Amantadine can interact with anticholinergic drugs, CNS stimulants, alcohol, and certain other medications. Consult a comprehensive drug interaction resource for detailed information. Avoid concomitant use of alcohol and other CNS depressants. Concomitant use of anticholinergics may worsen anticholinergic side effects. Use with CNS stimulants can increase the risk of CNS side effects like anxiety and insomnia.
Pregnancy and Breastfeeding
Amantadine is classified as Pregnancy Category C. It is not recommended during pregnancy unless the potential benefits outweigh the risks. Amantadine is excreted in breast milk. Breastfeeding is generally not recommended while taking amantadine.
Drug Profile Summary
- Mechanism of Action: Dopamine agonist and reuptake inhibitor, NMDA receptor antagonist, and inhibits viral uncoating (for influenza A, though no longer recommended due to resistance).
- Side Effects: Nausea, dizziness, insomnia, livedo reticularis, dry mouth; rarely NMS, psychosis, suicidal ideation.
- Contraindications: Hypersensitivity, end-stage renal disease (for extended-release formulations).
- Drug Interactions: Anticholinergics, CNS stimulants, alcohol.
- Pregnancy & Breastfeeding: Category C; not recommended.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Renal function, blood pressure, mental status (especially for signs of psychosis, depression, or suicidal ideation).
Popular Combinations
Amantadine is sometimes used in combination with other antiparkinsonian drugs like levodopa and carbidopa, though this can increase the risk of side effects like dyskinesias and psychosis.
Precautions
- General Precautions: Assess renal function, cardiac function, and mental status before initiating therapy. Monitor for side effects throughout treatment.
- Specific Populations: See Special Cases in Dosage section.
- Lifestyle Considerations: Advise patients to avoid alcohol and other CNS depressants. Caution about driving or operating machinery due to potential dizziness and drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Amantadine?
A: The dosage varies depending on the indication and patient factors. Refer to the detailed Dosage section above.
Q2: What are the common side effects of Amantadine?
A: Common side effects include nausea, dizziness, insomnia, livedo reticularis, dry mouth, and constipation.
Q3: Is Amantadine safe during pregnancy?
A: Amantadine is Pregnancy Category C and should be avoided during pregnancy unless the potential benefits outweigh the risks.
Q4: How does Amantadine work in Parkinson’s disease?
A: Amantadine increases dopamine levels in the brain by promoting dopamine release and inhibiting its reuptake. It also acts as an NMDA receptor antagonist.
Q5: Can Amantadine be used for Influenza A?
A: No, due to high rates of resistance, amantadine is no longer recommended for influenza A.
Q6: What are the serious side effects of Amantadine?
A: Serious side effects can include NMS, psychosis, suicidal thoughts and behavior, hallucinations, and orthostatic hypotension.
Q7: Does Amantadine interact with other medications?
A: Yes, Amantadine can interact with various medications, including anticholinergics and CNS stimulants. Consult a comprehensive drug interaction resource.
Q8: How should Amantadine be discontinued?
A: Amantadine should be tapered gradually to avoid withdrawal symptoms such as NMS-like reactions. Do not discontinue abruptly.
Q9: What should I monitor in patients taking Amantadine?
A: Monitor renal function, blood pressure, and mental status, paying close attention to signs of psychosis, depression, or suicidality.
