NUVIGIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NUVIGIL (NUVIGIL).
NUVIGIL (armodafinil) is the R-enantiomer of modafinil. Its precise mechanism is unknown, but it is thought to involve dopamine reuptake inhibition, leading to increased extracellular dopamine levels. It also affects other neurotransmitters such as norepinephrine, serotonin, and histamine.
| Metabolism | Primarily metabolized by amide hydrolysis, with minor contributions from CYP3A4/5. The major metabolite is armodafinil acid, which is inactive. |
| Excretion | Primarily renal excretion of metabolites and unchanged drug. Approximately 80% of a radiolabeled dose is recovered in urine over 7 days, with about 45% as unchanged armodafinil and 20% as the acid metabolite. Fecal excretion accounts for about 1%. |
| Half-life | The terminal elimination half-life of the (R)-enantiomer (armodafinil) is approximately 15 hours, compared to 12-15 hours for racemic modafinil. The half-life is prolonged in patients with hepatic impairment (Child-Pugh Class B or C: ~20-25 hours) and in elderly patients (up to 20 hours). Clinically, this supports once-daily dosing. |
| Protein binding | Moderate binding, approximately 60%, primarily to albumin. |
| Volume of Distribution | Volume of distribution (Vd) for armodafinil is approximately 0.8 L/kg (range 0.6-1.0 L/kg), suggesting distribution into total body water and some tissue binding. |
| Bioavailability | Oral bioavailability is essentially complete (estimated >95%), as absorption is extensive and first-pass metabolism is minimal (less than 10% of an oral dose is metabolized presystemically). |
| Onset of Action | Oral: Onset of wakefulness-promoting effect occurs within 30-60 minutes after ingestion. Peak plasma concentrations are achieved at 2 hours (range 1-4 hours) for the (R)-enantiomer. Subjective improvement in alertness is noted within 1-2 hours. |
| Duration of Action | Duration of wakefulness-promoting effect is approximately 12-15 hours following a single oral dose, consistent with the elimination half-life. Clinical studies demonstrate sustained improvement in wakefulness over the entire day with once-daily dosing. Duration may be shorter in patients with rapid metabolism. |
| Brand Substitutes | ME-PR Capsule, Pregabanyl Capsule, Pregacip M Capsule, Gabamax 75mg Capsule, Mahagaba-M 75 Capsule |
150 mg or 250 mg orally once daily in the morning.
| Dosage form | TABLET |
| Renal impairment | For severe chronic renal impairment (CrCl ≤20 mL/min): reduce dose to 100 mg once daily. |
| Liver impairment | Child-Pugh Class A or B: no adjustment necessary. Child-Pugh Class C: reduce dose to 100 mg once daily. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | Consider lower starting dose (e.g., 100 mg once daily) due to potential age-related renal impairment; titrate cautiously. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NUVIGIL (NUVIGIL).
| Breastfeeding | Excretion into human milk is likely. M/P ratio is unknown. Due to potential CNS stimulation in the infant, breastfeeding is not recommended during therapy. |
| Teratogenic Risk | First trimester: Increased risk of major congenital malformations, including oral clefts and cardiac defects, based on animal and limited human data. Second and third trimesters: Potential for fetal growth restriction and adverse neurodevelopmental outcomes. Risk is dose-dependent. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to armodafinil, modafinil, or any inactive ingredients in NUVIGIL"]
| Precautions | ["Serious skin reactions including Stevens-Johnson Syndrome (SJS) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported; discontinue at first sign of rash","Angioedema and hypersensitivity reactions; discontinue permanently if occur","Psychiatric symptoms including anxiety, mania, depression, psychosis, aggression, and suicidal ideation; use with caution in patients with history of psychiatric disorders","Cardiovascular effects including increased heart rate and blood pressure; avoid in patients with clinically significant cardiovascular conditions","Multiorgan hypersensitivity reactions; discontinue if suspected"] |
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| Monitor fetal growth via ultrasound and assess for congenital anomalies via targeted ultrasound. Perform echocardiography if exposure occurs in first trimester. Monitor maternal blood pressure and heart rate. |
| Fertility Effects | In animal studies, reduced fertility and increased preimplantation loss were observed. Human data are insufficient to determine effects on fertility. |