PROVIGIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PROVIGIL (PROVIGIL).
Nonselective dopamine reuptake inhibitor; activates the hypothalamic sleep-wake centers via dopaminergic, noradrenergic, and orexinergic pathways
| Metabolism | Hepatic via amide hydrolysis; primarily inactive metabolites; CYP3A4 minor role |
| Excretion | Primarily renal excretion as metabolites (80%); unchanged drug accounts for ~10%. Fecal elimination is minor (<5%). |
| Half-life | Terminal elimination half-life is approximately 15 hours in adults. Steady-state is achieved within 2-4 days. |
| Protein binding | Approximately 60% bound to plasma proteins, mainly albumin. |
| Volume of Distribution | Volume of distribution is about 0.8 L/kg, indicating distribution into total body water. |
| Bioavailability | Oral bioavailability is approximately 80% (almost complete). |
| Onset of Action | Oral: Onset of clinical effect occurs within 30-60 minutes post-dose. |
| Duration of Action | Duration of clinical effect is approximately 10-12 hours with single oral dose. Sustained with repeated dosing. |
100-200 mg orally once daily in the morning for narcolepsy and obstructive sleep apnea; 200 mg orally once daily in the morning for shift work disorder.
| Dosage form | TABLET |
| Renal impairment | For creatinine clearance < 30 mL/min: reduce dose to 100 mg once daily. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: not recommended. |
| Pediatric use | Not approved for use in children < 17 years; safety and efficacy not established. |
| Geriatric use | Start at 100 mg once daily due to potential for decreased renal function; monitor for agitation and sleep disturbances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PROVIGIL (PROVIGIL).
| Breastfeeding | Modafinil is excreted into human milk in small amounts (M/P ratio not established; estimated infant dose ~0.1-0.6% of maternal weight-adjusted dose). No adverse effects reported in breastfed infants, but due to potential CNS stimulation effects in infants, caution advised. Consider alternative therapies or avoid breastfeeding during therapy. |
| Teratogenic Risk | First trimester: Avoid use; limited human data suggest possible increased risk of major congenital malformations (e.g., cardiac anomalies) from studies with similar drugs (armodafinil). Second and third trimesters: There is no adequate evidence of fetal harm, but animal studies show developmental toxicity (reduced fetal weight, increased skeletal variations) at clinically relevant doses. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to modafinil or its components","Use of cyclosporine (contraindicated due to CYP3A4 induction)"]
| Precautions | ["Serious rash including Stevens-Johnson syndrome","Angioedema and anaphylaxis","Multi-organ hypersensitivity reactions","Psychiatric symptoms (psychosis, mania, aggression, suicidal ideation)","Cardiovascular risks including increased heart rate and blood pressure","Hepatic injury","Monitor for misuse or abuse potential"] |
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| Fetal Monitoring | Regular monitoring of blood pressure, heart rate, and fetal growth parameters (ultrasound) recommended. Assess for signs of maternal insomnia or psychiatric side effects. Neonatal monitoring for symptoms of withdrawal or CNS stimulation post-delivery. |
| Fertility Effects | Animal studies: No significant impairment of fertility at recommended doses. Human data: Limited. Potential for reduced contraceptive efficacy due to CYP3A4 induction; advise non-hormonal or additional barrier methods. No direct evidence of adverse effects on human fertility. |