TASIMELTEON
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TASIMELTEON (TASIMELTEON).
Tasimelteon is a selective melatonin MT1 and MT2 receptor agonist that mimics the natural sleep-promoting effects of melatonin by modulating circadian rhythms. It binds to MT1 receptors to promote sleep onset and to MT2 receptors to phase-shift the circadian clock.
| Metabolism | Primarily metabolized by CYP1A2 and CYP3A4, with minor contributions from CYP2C9 and CYP2C19. |
| Excretion | Primarily hepatic metabolism via CYP1A2 and CYP3A4; <0.1% excreted unchanged in urine; fecal excretion accounts for ~80% of total clearance as metabolites. |
| Half-life | 1.3 hours (range 0.5–2.0 h); short half-life consistent with use for sleep initiation without residual sedation. |
| Protein binding | ~90–94% bound to serum albumin; binding is independent of drug concentration. |
| Volume of Distribution | ~1.6 L/kg (range 1.2–2.0 L/kg); indicates extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is ~1.2–7.4% (due to extensive first-pass metabolism); higher absolute bioavailability expected with sublingual formulation but commercial product is oral only. |
| Onset of Action | Oral: ~30 minutes to measurable effects; peak plasma concentration at 0.5–1.5 hours after dosing. |
| Duration of Action | 3–4 hours based on receptor occupancy; clinical effect duration supports single dosing at bedtime without next-day impairment. |
20 mg orally once daily at bedtime, taken within 30 minutes of retiring and at the same time each night. Not to be taken with or immediately after a high-fat meal.
| Dosage form | CAPSULE |
| Renal impairment | For severe renal impairment (eGFR 15-29 mL/min/1.73 m2): reduce dose to 10 mg once daily. For end-stage renal disease (eGFR <15 mL/min/1.73 m2) or on dialysis: not recommended. No adjustment for mild to moderate impairment (eGFR ≥30). |
| Liver impairment | For moderate hepatic impairment (Child-Pugh class B): reduce dose to 10 mg once daily. For severe hepatic impairment (Child-Pugh class C): not recommended. No adjustment for mild impairment (Child-Pugh class A). |
| Pediatric use | Not approved for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No specific dose adjustment recommended based on age alone. However, clinical studies showed higher exposure in elderly patients; monitor for adverse effects and consider starting at 10 mg if tolerability concerns. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TASIMELTEON (TASIMELTEON).
| Breastfeeding | No data on tasimelteon excretion in human milk. Based on molecular weight (401.5 Da), low protein binding (~82%), and high lipophilicity, it is likely to distribute into breast milk. M/P ratio unknown. Breastfeeding not recommended during therapy. Consider discontinuing drug or formula feeding given potential for infant sedation and unknown effects on circadian rhythms. |
| Teratogenic Risk | FDA Pregnancy Category C. In animal studies, tasimelteon administered during organogenesis resulted in increased postimplantation loss and reduced fetal body weight at doses ≥10 mg/kg/day (approximately 5 times the human exposure at the MRHD of 20 mg). In rabbits, increased resorptions and reduced fetal weights were observed at 25 mg/kg/day (~50 times MRHD). There are no adequate and well-controlled studies in pregnant women. First trimester: theoretical risk based on animal data; second/third trimester: limited data; potential for fetal harm cannot be ruled out. Use only if benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to tasimelteon or any component of the formulation."]
| Precautions | ["May cause somnolence; advise patients not to engage in activities requiring mental alertness (e.g., driving) after taking tasimelteon.","May impair reproductive function in females of childbearing potential based on animal studies.","Not recommended for use in patients with severe hepatic impairment."] |
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| Fetal Monitoring | Monitor for maternal sedation, dizziness, and potential QT prolongation (tasimelteon may increase QTc interval at higher exposures). Fetal monitoring: consider fetal growth ultrasound if prolonged use during pregnancy. No specific fetal monitoring required, but assess for any signs of fetal distress in third trimester if used near term. |
| Fertility Effects | In animal studies, tasimelteon had no significant effects on male or female fertility at exposures up to 6 times the MRHD. Human data are lacking. Theoretical possibility of altered circadian rhythms affecting menstrual cycles or spermatogenesis; no evidence of impairment. Advise patients seeking pregnancy to discuss timing of therapy. |