FLUMADINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FLUMADINE (FLUMADINE).
Rimantadine inhibits the replication of influenza A virus by blocking the M2 ion channel, thereby preventing viral uncoating and the release of viral RNA into host cells. It also has weak NMDA receptor antagonist properties.
| Metabolism | Extensively metabolized in the liver via hydroxylation and conjugation, primarily by cytochrome P450 isoenzymes (notably CYP3A4), with less than 25% excreted unchanged in urine. |
| Excretion | Renal: 85% unchanged via glomerular filtration and tubular secretion; Fecal: <5% |
| Half-life | Terminal elimination half-life: 16-48 hours (mean ~24 hours). In elderly (>70 years) or severe renal impairment (CrCl <10 mL/min), half-life may exceed 100 hours, requiring dose reduction. |
| Protein binding | 45-50% binding to albumin |
| Volume of Distribution | Vd: 3-8 L/kg (mean ~5 L/kg), indicating extensive tissue distribution, particularly in respiratory secretions. |
| Bioavailability | Oral: 90-100% (well absorbed); IV: 100%. |
| Onset of Action | Oral: ~30-60 minutes for antiviral effect; peak plasma concentration at 2-6 hours. |
| Duration of Action | 12-24 hours based on plasma levels above MIC for influenza A; clinical effect persists for 24-48 hours after single dose. |
100 mg orally twice daily for 7-10 days; initiate within 48 hours of symptom onset.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: 100 mg once daily; GFR 15-29 mL/min: 100 mg every 48 hours; GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B or C: 100 mg once daily (limited data; monitor for toxicity). |
| Pediatric use | Children ≥10 years: 100 mg twice daily; children 1-9 years: 5 mg/kg/day (max 150 mg/day) divided twice daily; not recommended for children <1 year. |
| Geriatric use | In patients ≥65 years, consider 100 mg once daily due to increased risk of CNS effects; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FLUMADINE (FLUMADINE).
| Breastfeeding | No human data; drug likely excreted in breast milk (M/P ratio unknown). Caution due to potential for infant adverse effects (e.g., nausea, dizziness). Consider benefits of breastfeeding vs. risk of infant exposure. |
| Teratogenic Risk | Pregnancy Category C. Animal studies (rats and rabbits) at doses up to 10-20 mg/kg/day (1.3-2.6 times the human dose) showed embryotoxicity, fetotoxicity, and increased incidence of fetal malformations (e.g., skeletal anomalies, cleft palate). No adequate human studies. Avoid use in first trimester unless benefit justifies risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to rimantadine or adamantane derivatives","Severe renal impairment (CrCl < 10 mL/min) or end-stage renal disease (if not on dialysis)","Concurrent use of live attenuated influenza vaccine (LAIV) due to potential interference"]
| Precautions | ["May cause central nervous system effects (e.g., nervousness, anxiety, insomnia, difficulty concentrating)","Caution in patients with renal impairment (dose adjustment required for CrCl < 30 mL/min)","Caution in patients with hepatic impairment","Seizure risk, especially in patients with a history of seizures","Not recommended for use in elderly nursing home patients with underlying medical conditions due to emergence of resistant virus"] |
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| Fetal Monitoring |
| Monitor for maternal adverse effects (e.g., CNS disturbances, nausea). Fetal monitoring indicated if used after 20 weeks gestation (ultrasound for growth and anomalies). No specific fetal heart rate monitoring required. |
| Fertility Effects | No human fertility studies; animal studies (rats) at high doses showed reduced fertility and increased preimplantation loss. Potential for reversible suppression of spermatogenesis in males based on animal data. |