AMANTADINE
Clinical safety rating: caution
Animal studies have proved adverse effects but may be safe for humans
Amantadine is an antiviral and antiparkinsonian agent. Its antiviral mechanism involves inhibition of viral uncoating, thereby blocking influenza A M2 ion channel. In Parkinson's disease, it is thought to increase dopamine release and inhibit its reuptake, and may also have anticholinergic and NMDA receptor antagonist effects.
| Metabolism | Amantadine is primarily excreted unchanged in urine via glomerular filtration and tubular secretion. It undergoes minimal hepatic metabolism (less than 10%) with no major identified metabolites. |
| Excretion | Renal: 90% as unchanged drug via glomerular filtration and tubular secretion; fecal: <10% |
| Half-life | Terminal elimination half-life: 10-14 hours in young adults, up to 24 hours in elderly; prolonged to >24 hours in renal impairment |
| Protein binding | 60-70% bound, primarily to albumin |
| Volume of Distribution | Vd: 4-10 L/kg; indicates extensive tissue binding and penetration into brain (CSF: 50-80% of plasma concentration) |
| Bioavailability | Oral: 86-90%; IV: 100% |
| Onset of Action | Oral: 4-8 hours for peak effect; IV: within 1-2 hours; topical (not standard) |
| Duration of Action | 12-24 hours; clinical effects persist for 6-12 hours after single dose, longer with accumulation |
| Molecular Weight | 151.25 |
100 mg orally twice daily for Parkinson's disease; 100 mg orally twice daily for influenza A prophylaxis/treatment (up to 200 mg/day).
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | CrCl 30-50 mL/min: 100 mg once daily; CrCl 15-29 mL/min: 100 mg every other day; CrCl <15 mL/min or hemodialysis: 200 mg every 7 days. |
| Liver impairment | No specific Child-Pugh adjustments; use caution in severe hepatic impairment due to potential toxicity. |
| Pediatric use | Influenza A prophylaxis/treatment: 1-9 years: 5 mg/kg/day (max 150 mg/day) in 2 divided doses; 10-12 years: 100 mg twice daily; 13-16 years: 100 mg twice daily. Parkinson's: not recommended. |
| Geriatric use | Use lower starting dose (100 mg daily) due to age-related renal decline; frequent monitoring for neuropsychiatric effects. |
| 1st trimester | Amantadine is teratogenic in animal studies; human data limited. Avoid use in first trimester unless benefit outweighs risk. Associated with cardiovascular malformations. |
| 2nd trimester | Use only if clearly needed. Limited human data; potential for fetal harm. |
| 3rd trimester | May cause neonatal withdrawal symptoms (jitteriness, respiratory distress). Avoid near term. |
Clinical note
Anticholinergic drugs may have additive side effects Use cautiously in patients with seizure history or psychiatric disorders livedo reticularis and ankle edema are common.
| Placental transfer | Amantadine crosses the placenta; fetal concentrations similar to maternal. |
| Breastfeeding | Amantadine is excreted into breast milk in low concentrations. May cause irritability, vomiting, urinary retention in infant. Avoid breastfeeding or use with caution. |
■ FDA Black Box Warning
None.
| Common Effects | influenza A |
| Serious Effects |
History of hypersensitivity to amantadineSevere uncontrolled psychosisConcurrent use of live attenuated influenza vaccine
| Precautions | Can cause CNS effects such as confusion, hallucinations, and seizures, especially in elderly or those with renal impairment, May exacerbate psychiatric disorders, Abrupt discontinuation may precipitate parkinsonian crisis or neuroleptic malignant syndrome in patients with Parkinson's disease, Avoid in patients with uncontrolled epilepsy, Renal dose adjustment required |
| Food/Dietary | No specific food interactions. Avoid alcohol and limit caffeine intake due to potential increased CNS effects. Take with food if gastrointestinal upset occurs. |
Loading safety data…
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Associated with cardiovascular malformations (e.g., Ebstein anomaly) in retrospective studies; risk approximately 1-2% absolute. Second and third trimesters: Limited data; theoretical risk of fetal tachyarrhythmia and neurobehavioral effects. Human data insufficient to exclude risk. |
| Fetal Monitoring | Monitor maternal renal function (CrCl), ECG for arrhythmias, CNS effects (dizziness, confusion), and fetal ultrasound for cardiac anomalies. Third trimester: fetal heart rate monitoring for tachyarrhythmia. |
| Fertility Effects | Animal studies suggest no significant impairment of fertility. Human data sparse; theoretical effect on sperm motility and ovulation due to dopaminergic activity, but clinical significance unknown. |
| Clinical Pearls | Amantadine is an antiviral and antiparkinsonian agent with NMDA receptor antagonist properties. For Parkinson's disease, it improves dyskinesias, especially levodopa-induced dyskinesias. For influenza A, it is less effective than neuraminidase inhibitors and resistance is common. Monitor for CNS effects (confusion, hallucinations, nightmares) especially in elderly or renally impaired patients. Dose adjustment required for CrCl <50 mL/min. Do not discontinue abruptly in Parkinson's disease due to risk of neuroleptic malignant syndrome. |
| Patient Advice | Take exactly as prescribed; do not stop suddenly without consulting your doctor. · Avoid alcohol as it may increase dizziness or confusion. · Report any unusual thoughts, hallucinations, or severe confusion to your healthcare provider immediately. · If you have Parkinson's disease, this medicine helps control symptoms but does not cure it. · If you are taking for influenza, finish the full course even if you feel better. · May cause blurred vision or dizziness; avoid driving or operating machinery until you know how it affects you. · Stay hydrated but avoid excessive caffeine as it may exacerbate side effects. |