NAMENDA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NAMENDA (NAMENDA).
Memantine is an uncompetitive, low-affinity N-methyl-D-aspartate (NMDA) receptor antagonist. It binds to the NMDA receptor at the magnesium binding site and blocks excessive glutamate-mediated excitotoxicity while allowing normal physiological neurotransmission.
| Metabolism | Partially hepatic via cytochrome P450 enzymes (CYP2B6, CYP3A4, CYP2C9, CYP2D6); minimal metabolism; 75-90% excreted unchanged in urine. |
| Excretion | Primarily renal (hydrochlorothiazide: 70% unchanged; metolazone: 80% unchanged; chlorthalidone: 50% unchanged). Biliary/fecal elimination minimal (<10%). |
| Half-life | Thiazide-like: chlorthalidone 40-60 h (prolonged due to RBC binding); thiazide: hydrochlorothiazide 6-15 h (clinical effect persists due to prolonged renal action). |
| Protein binding | Hydrochlorothiazide: 40-68% bound to albumin; chlorthalidone: 75% bound to albumin and erythrocytes; metolazone: 50-70% bound to albumin. |
| Volume of Distribution | Hydrochlorothiazide: 3-4 L/kg; chlorthalidone: 3-4 L/kg (large due to RBC binding); metolazone: 1-2 L/kg. |
| Bioavailability | Hydrochlorothiazide: 65-75%; chlorthalidone: ~65%; metolazone: ~65% (approximately dose proportional). |
| Onset of Action | Oral: diuresis begins within 2 h; peak effect at 4-6 h. IV: not available. Antihypertensive effect: 3-4 days for full effect. |
| Duration of Action | Hydrochlorothiazide: 6-12 h; chlorthalidone: 24-72 h (allows QD dosing). Clinical note: antihypertensive effect may last >24 h despite shorter half-life. |
Initial: 5 mg orally once daily; increase by 5 mg/day every 4 weeks to target dose of 10 mg twice daily (total 20 mg/day).
| Dosage form | TABLET |
| Renal impairment | CrCl 30-49 mL/min: target dose 5 mg twice daily; CrCl 5-29 mL/min: target dose 5 mg once daily. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe impairment (Child-Pugh C). |
| Pediatric use | Not approved for use in pediatric patients. |
| Geriatric use | No specific dose adjustments based on age alone; consider renal function and concomitant medications due to increased risk of adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NAMENDA (NAMENDA).
| Breastfeeding | Unknown if excreted in human breast milk. M/P ratio not available. Caution advised; consider risk vs benefit. |
| Teratogenic Risk | Pregnancy Category B: No evidence of risk in humans based on animal studies, but adequate human studies are lacking. There is no known teratogenic risk in any trimester; however, use only if clearly needed. |
| Fetal Monitoring | Monitor maternal renal function and signs of NMDA receptor antagonism (e.g., confusion, dizziness). No specific fetal monitoring required. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to memantine or any component of the formulation","Severe renal impairment (CrCl < 5 mL/min)"]
| Precautions | ["Increased risk of seizures in patients with predisposing factors","Renal impairment requires dose adjustment; contraindicated in severe renal impairment (CrCl < 5 mL/min)","Caution in patients with urinary tract conditions or conditions that increase urine pH (e.g., alkali therapy, severe urinary tract infections, renal tubular acidosis) leading to reduced elimination","Potential for increased adverse reactions if concomitant use with other NMDA antagonists (e.g., amantadine, ketamine, dextromethorphan)"] |
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| Fertility Effects | No known effect on fertility in animal studies. No human data available. |