NAMZARIC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NAMZARIC (NAMZARIC).
Memantine is an NMDA receptor antagonist that noncompetitively binds to NMDA receptors, blocking excessive glutamate activity and preventing excitotoxicity. Donepezil is a reversible acetylcholinesterase inhibitor that increases acetylcholine levels in the brain.
| Metabolism | Memantine: Limited hepatic metabolism, primarily CYP450 independent, with small contribution from CYP2B6 and CYP2D6. Donepezil: Extensively metabolized by CYP3A4 and CYP2D6. |
| Excretion | Namzaric (memantine/donepezil) undergoes dual elimination: memantine is primarily renally excreted (75-90% unchanged, with tubular secretion) and donepezil is hepatically metabolized (CYP3A4 and 2D6) and excreted in urine (17% unchanged) and feces (15% as metabolites). |
| Half-life | Memantine terminal half-life: 60-80 hours (prolonged in renal impairment, requiring dose adjustment). Donepezil terminal half-life: ~70 hours (linear kinetics at steady state). |
| Protein binding | Memantine: 45% bound to plasma proteins (mainly albumin). Donepezil: 96% bound (to albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Memantine: Vd 8-12 L/kg, indicating extensive extravascular distribution. Donepezil: Vd 12-16 L/kg, also widely distributed. |
| Bioavailability | Oral: memantine ~100% bioavailability; donepezil ~100% bioavailability (tablet formulation). |
| Onset of Action | Oral: clinical cognitive effects observed within 4-8 weeks for donepezil; memantine effects may require 12-24 weeks for full benefit. |
| Duration of Action | Once-daily dosing provides 24-hour cholinesterase inhibition for donepezil; memantine's NMDA receptor modulation is continuous with sustained exposure. |
Namzaric (memantine ER + donepezil) is dosed as one capsule orally once daily in the evening. The usual starting dose is 7 mg memantine/10 mg donepezil, titrated weekly to 14 mg/10 mg, then 21 mg/10 mg, then 28 mg/10 mg as tolerated.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | For severe renal impairment (CrCl 5-29 mL/min), target maintenance dose is 14 mg memantine/10 mg donepezil once daily; titration should not exceed 14 mg/10 mg. For CrCl <5 mL/min, not recommended. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C); use with caution. |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established in patients under 18 years. |
| Geriatric use | No specific dose adjustment recommended solely for age; initiate at lowest dose and titrate slowly due to increased risk of adverse effects in elderly (e.g., falls, bradycardia). |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NAMZARIC (NAMZARIC).
| Breastfeeding | No data on presence in human milk; M/P ratio unknown. Consider developmental and health risks of breastfeeding versus drug exposure; use caution. |
| Teratogenic Risk | Pregnancy Category C. First trimester: limited human data; animal studies show developmental toxicity at doses similar to human exposure. Second and third trimesters: known increased risk of fetal cholinergic crisis. Not recommended unless benefit outweighs risk. Advise adequate contraception. |
| Fetal Monitoring |
■ FDA Black Box Warning
No black box warning.
| Common Effects | Nausea Stomach irritation Dryness in mouth Fatigue Dizziness Sleepiness Allergic reaction Nervousness Insomnia difficulty in sleeping Restlessness Headache |
| Serious Effects |
["Hypersensitivity to memantine, donepezil, or piperidine derivatives","Concurrent use with drugs known to cause QTc prolongation (donepezil)"]
| Precautions | ["Risk of bradycardia and heart block due to donepezil's vagotonic effect","Risk of seizures","Risk of peptic ulcer disease and gastrointestinal bleeding (donepezil)","Genitourinary effects: urinary obstruction (memantine)","Potential for neuroleptic malignant syndrome (NMS) and malignant hyperthermia with abrupt discontinuation","Use in renal impairment requires dose adjustment for memantine","Use in hepatic impairment requires caution"] |
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| Monitor for maternal cholinergic adverse effects (e.g., bradycardia, hypotension, seizures, excessive salivation). Assess fetal growth and well-being via ultrasound. Monitor for fetal heart rate abnormalities during labor. Postnatal monitoring for infant cholinergic symptoms. |
| Fertility Effects | No specific human fertility data. Animal studies show no significant effects on fertility. Theoretical risk of cholinergic disruption of ovulation or implantation; uncertain clinical significance. |