SYMMETREL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYMMETREL (SYMMETREL).
Inhibits influenza A virus uncoating and viral RNA replication; increases dopamine release and blocks dopamine reuptake in the CNS.
| Metabolism | Primarily excreted unchanged in urine; minor hepatic acetylation. |
| Excretion | Primarily renal excretion (90-95% unchanged) via glomerular filtration and tubular secretion; minor fecal (<5%). Dose adjustment required in renal impairment. |
| Half-life | Terminal half-life: 24-48 hours (young adults); 48-72 hours (elderly); may extend to 7-10 days in severe renal impairment. Clinically, steady-state achieved in 4-7 days. |
| Protein binding | Approximately 67% bound to serum proteins (mainly albumin). |
| Volume of Distribution | Vd: 3-8 L/kg; large distribution suggests extensive tissue binding, particularly in lungs, kidneys, and brain (crosses blood-brain barrier). |
| Bioavailability | Oral bioavailability: 50-90% (variable due to first-pass metabolism); well absorbed from GI tract. |
| Onset of Action | Oral: 48-72 hours for therapeutic effect in Parkinson's disease; 4-6 hours for influenza A antiviral effect. |
| Duration of Action | Therapeutic effect persists for 24-48 hours after last dose in Parkinson's; antiviral effect typically continues for several days but resistance may develop. Duration prolonged in renal impairment. |
| Molecular Weight | 151.25 |
100 mg orally twice daily; may increase to 200 mg orally twice daily if tolerated, usually in divided doses. For Parkinson's disease, 100 mg orally twice daily; for drug-induced extrapyramidal reactions, 100 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: 100 mg once daily. CrCl 15-29 mL/min: 100 mg every 48 hours. CrCl <15 mL/min or hemodialysis: 200 mg every 7 days. |
| Liver impairment | No specific Child-Pugh based adjustments are established; use with caution in severe hepatic impairment. |
| Pediatric use | Children <1 year: not recommended. 1-9 years: 4.4-8.8 mg/kg/day orally in 2 divided doses, max 150 mg/day. 9-12 years: 100 mg orally twice daily. ≥12 years: adult dosing. |
| Geriatric use | Start at 100 mg once daily in elderly patients due to reduced renal function and increased risk of CNS effects; increase slowly if needed. |
| 1st trimester | Amantadine is teratogenic in animal studies. Human data limited; risk of cardiovascular malformations. Use only if benefit outweighs risk. |
| 2nd trimester | May cause harm; consider alternative therapy. Not recommended unless essential. |
| 3rd trimester | May cause neonatal withdrawal symptoms; use near term is contraindicated. |
Clinical note
Comprehensive clinical and safety monograph for SYMMETREL (SYMMETREL).
| Placental transfer | Amantadine crosses the placenta; detected in fetal serum at concentrations similar to maternal serum. |
| Breastfeeding | Amantadine is excreted into breast milk. Potential for serious adverse effects in nursing infants, including vomiting, urinary retention, rash, and central nervous system effects. Contraindicated during breastfeeding. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to amantadine or any componentNursing mothersSevere uncontrolled psychosisSevere renal impairment (CrCl <15 mL/min)Neonates and infants <1 year
| Precautions | May cause CNS effects including confusion, hallucinations, and seizures; use caution in renal impairment, elderly, and seizure disorders; suicidal ideation; neuroleptic malignant syndrome if abruptly discontinued. |
| Food/Dietary | No specific food interactions reported. However, alcohol consumption may potentiate CNS side effects (dizziness, drowsiness). Avoid excessive caffeine as it may worsen side effects. |
| Clinical Pearls |
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| Lactation Rating |
| L5 (Contraindicated) |
| Teratogenic Risk | SYMMETREL (amantadine) is classified as FDA Pregnancy Category C. Animal studies have shown teratogenic effects including skeletal and visceral malformations at high doses. Human data are limited, but reports suggest an increased risk of cardiovascular malformations when used in the first trimester. Use during the second and third trimesters may be associated with fetal tachycardia, edema, and transient neonatal withdrawal. Amantadine should be avoided during pregnancy unless clearly needed. |
| Fetal Monitoring | Monitor the mother for signs of toxicity (CNS effects, arrhythmias, edema) and fetal growth via ultrasound if used during pregnancy. For neonates exposed in utero, observe for withdrawal symptoms (e.g., irritability, poor feeding) and cardiac effects. Obtain baseline maternal renal function due to drug excretion. |
| Fertility Effects | Amantadine has been associated with altered menstrual cycles and potential effects on sperm quality in animal studies. Human data are insufficient to determine a direct effect on fertility, but caution is advised for those attempting conception. |
| Amantadine (Symmetrel) is primarily used for Parkinson's disease and drug-induced extrapyramidal symptoms. It has antiviral activity against influenza A but is no longer recommended due to widespread resistance. Use with caution in renal impairment; dose adjustment required for CrCl <50 mL/min. May cause livedo reticularis, peripheral edema, and anticholinergic effects like dry mouth and urinary retention. Avoid abrupt discontinuation due to risk of parkinsonian crisis. |
| Patient Advice | Take exactly as prescribed, usually 1-2 times daily with or without food. Do not double doses. · Avoid alcohol as it may increase dizziness or drowsiness. · Report any swelling, skin discoloration, or vision changes to your doctor immediately. · Do not stop taking this medication suddenly; tapering is required under medical supervision. · If you have kidney disease, inform your doctor so appropriate dose adjustments can be made. · This medication may cause drowsiness or blurred vision; avoid driving until you know how it affects you. |