SYMADINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SYMADINE (SYMADINE).
SYMADINE (amantadine) is a tricyclic amine that inhibits influenza A virus replication by blocking the viral M2 ion channel, which prevents uncoating of viral RNA. It also increases dopamine release and inhibits dopamine reuptake in the CNS, providing antiparkinsonian effects.
| Metabolism | Amantadine is primarily excreted unchanged in urine via glomerular filtration and tubular secretion. Minor metabolism via N-acetylation and hydroxylation has been reported, but specific enzymes are not well characterized. |
| Excretion | Renal elimination of unchanged drug accounts for approximately 90% of the administered dose. Biliary/fecal excretion is minimal (<5%). |
| Half-life | The terminal elimination half-life is approximately 24 hours in patients with normal renal function. In patients with renal impairment (CrCl <50 mL/min), the half-life is significantly prolonged, requiring dose adjustment. The long half-life allows for once-daily dosing. |
| Protein binding | Approximately 67% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | The apparent volume of distribution is approximately 5–10 L/kg, indicating extensive tissue distribution and penetration into the CNS. |
| Bioavailability | Oral bioavailability is 90–100%, indicating nearly complete absorption. No significant first-pass metabolism. |
| Onset of Action | For oral administration, clinical effect typically begins within 48 hours. For intravenous administration (if applicable), onset is more rapid, within hours. In Parkinson's disease, improvement in symptoms may be observed within the first few days. |
| Duration of Action | Duration of clinical effect is approximately 24 hours, supporting once-daily dosing. Clinical benefits are maintained with consistent dosing. In antiviral use, duration covers the treatment course. |
| Molecular Weight | 216.32 |
100 mg orally every 12 hours; immediate-release formulation.
| Dosage form | CAPSULE |
| Renal impairment | CrCl 30-50 mL/min: 100 mg every 24 hours; 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 | 1-9 years: 4.4-8.8 mg/kg/day divided every 12 hours, max 150 mg/day; ≥10 years: same as adult. |
| Geriatric use | Reduce dose or extend interval due to age-related renal decline; consider starting at 100 mg daily. |
| 1st trimester | Insufficient human data; animal studies show risk. Avoid use in first trimester unless benefit outweighs risk. |
| 2nd trimester | Limited human data; potential for antiviral-related adverse effects. Use only if clearly needed. |
| 3rd trimester | Limited data; may cause neonatal adaptation syndrome if used near term. Avoid in third trimester unless essential. |
Clinical note
Comprehensive clinical and safety monograph for SYMADINE (SYMADINE).
| Placental transfer | SYMADINE crosses the placenta in humans. Placental transfer has been documented with measurable cord blood levels approximately 50% of maternal serum concentrations. |
| Breastfeeding | SYMADINE is excreted into human breast milk. Due to potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to SYMADINE or any component of the formulationConcurrent use with live attenuated influenza vaccine (nasal) due to risk of viral replicationHistory of seizures or psychotic disorders
| Precautions | May cause CNS effects including dizziness, confusion, and hallucinations; caution in elderly and patients with renal impairment; neuroleptic malignant syndrome-like symptoms reported with abrupt discontinuation; suicidal ideation and depression; orthostatic hypotension; peripheral edema; rare episodes of acute angle-closure glaucoma in patients with untreated narrow-angle glaucoma. |
| Food/Dietary | No significant food interactions. Avoid excessive caffeine as it may exacerbate side effects like insomnia and nervousness. |
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| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | Pregnancy Category C. First trimester: Risk of teratogenicity cannot be ruled out; animal studies show fetal harm but human data insufficient. Second and third trimesters: Potential for neonatal hypotension, bradycardia, respiratory depression, and hypoglycemia with chronic use. |
| Fetal Monitoring | Monitor maternal heart rate and blood pressure, fetal heart rate, and uterine activity during use. Assess for signs of preterm labor or fetal distress. |
| Fertility Effects | No specific studies on human fertility. Animal studies have not shown impaired fertility. However, beta-blockers may theoretically affect spermatogenesis or menstrual cycle. |
| Clinical Pearls | SYMADINE (amantadine) is an antiviral and antiparkinsonian agent. Monitor for CNS effects (e.g., confusion, hallucinations) especially in elderly or renally impaired. Adjust dose in renal impairment (CrCl <50 mL/min). Avoid abrupt discontinuation in Parkinson's disease. May cause orthostatic hypotension; advise rising slowly. Drug interactions: anticholinergics increase adverse effects; avoid alcohol. |
| Patient Advice | Take exactly as prescribed; do not change dose without consulting doctor. · Avoid alcohol and limit caffeine intake. · Rise slowly from sitting or lying to prevent dizziness. · Report confusion, hallucinations, or difficulty urinating immediately. · Do not stop taking suddenly without doctor's guidance. · If you miss a dose, skip it unless it's nearly time for the next dose; do not double up. |