Note: Effect may not occur for weeks or months due to differences in circadian rhythms. Capsules and oral suspension are not interchangeable.
Nighttime sleep disturbances in Smith-Magenis syndrome: Oral (capsules): 20 mg once daily 1 hour prior to bedtime; take at the same time each night.
Non-24-hour sleep-wake disorder : Oral (capsules): 20 mg once daily 1 hour prior to bedtime; take at the same time each night.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Mild or moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in manufacturer’s labeling (has not been studied). Use is not recommended.
(For additional information see "Tasimelteon: Pediatric drug information")
Note: Formulations of tasimelteon (capsules vs oral suspension) are not interchangeable on a mg:mg basis.
Nighttime sleep disturbances in Smith-Magenis syndrome (SMS):
Children ≥3 years and Adolescents <16 years: Oral: Oral suspension:
≤28 kg: 0.7 mg/kg/dose once daily 1 hour before bedtime.
>28 kg: 20 mg once daily 1 hour before bedtime.
Adolescents ≥16 years: Oral: Capsule: 20 mg once daily 1 hour before bedtime.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no pediatric-specific dosage adjustments provided in the manufacturer's labeling (has not been studied); based on adult data, dosage adjustment is likely unnecessary.
Children ≥3 years and Adolescents:
Mild or moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in manufacturer's labeling (has not been studied). Use is not recommended.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Hetlioz: 20 mg [contains fd&c blue #1 (brilliant blue), fd&c yellow #6 (sunset yellow)]
Suspension, Oral:
Hetlioz LQ: 4 mg/mL (48 mL, 158 mL) [contains polysorbate 80, sodium benzoate; cherry flavor]
No
Hetlioz LQ oral suspension: FDA approved December 2020; availability anticipated in the first quarter of 2021.
Administer orally without food. Should be taken at the same time every night 1 hour before bedtime. Swallow capsule whole. After administration, activities should be limited to preparing for sleep. If the dose cannot be taken at approximately the same time on a given night, that dose should be skipped. Capsules and oral suspension are not interchangeable.
Oral: Administer without food at the same time every night, 1 hour before bedtime. After administration, activities should be limited to preparing for sleep. If the dose cannot be taken at approximately the same time on a given night, that dose should be skipped.
Capsule: Adolescents ≥16 years: Swallow capsule whole.
Oral suspension: Children ≥3 years and Adolescents <16 years: Shake suspension well for ≥30 seconds prior to use; measure dose using provided oral syringe. After use, leave bottle adapter in place and replace bottle cap; rinse plunger and syringe with water and allow to air dry.
Nighttime sleep disturbances in Smith-Magenis syndrome: Treatment of nighttime sleep disturbances in Smith-Magenis syndrome patients ≥16 years of age (capsules) or 3 to 15 years of age (oral suspension).
Non-24-hour sleep-wake disorder (capsules): Treatment of non-24-hour sleep-wake disorder (non-24). Note: Efficacy was established in totally blind patients with non-24-hour sleep-wake disorder.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Nervous system: Headache (17%)
1% to 10%:
Genitourinary: Urinary tract infection (7%)
Hepatic: Increased serum alanine aminotransferase (10%)
Nervous system: Abnormal dreams (≤10%), nightmares (≤10%)
Respiratory: Upper respiratory tract infection (7%)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• CNS depression: May cause CNS depression impairing physical and mental capabilities; patients must be cautioned about performing tasks that require mental alertness (operating machinery or driving).
Disease-related concerns:
• Hepatic impairment: Use is not recommended in patients with severe hepatic impairment.
Special populations:
• Older adult: Use with caution in the elderly; exposure is increased; may increase the risk of adverse events.
• Smokers: Smoking causes induction of CYP1A2 levels; tasimelteon exposure is decreased in smokers compared to nonsmokers, which may reduce tasimelteon efficacy.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol and/or sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol and/or benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Product interchangeability: Oral formulations of tasimelteon (capsules versus oral suspension) are not interchangeable on a mg:mg basis.
Substrate of CYP1A2 (major), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Beta-Blockers: May diminish the therapeutic effect of Tasimelteon. Management: Consider avoiding nighttime administration of beta-blockers during tasimelteon therapy due to the potential for reduced tasimelteon efficacy. Risk D: Consider therapy modification
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Broccoli: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cannabis: May decrease the serum concentration of CYP1A2 Substrates (High risk with Inducers). Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
CYP1A2 Inducers (Moderate): May decrease the serum concentration of Tasimelteon. Risk C: Monitor therapy
CYP1A2 Inhibitors (Moderate): May increase the serum concentration of Tasimelteon. Risk C: Monitor therapy
CYP1A2 Inhibitors (Strong): May increase the serum concentration of Tasimelteon. Risk X: Avoid combination
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Tasimelteon. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Tasimelteon. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Tasimelteon. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Melatonin: May enhance the sedative effect of Hypnotics (Nonbenzodiazepine). Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: Hypnotics (Nonbenzodiazepine) may enhance the CNS depressant effect of Oxybate Salt Products. Risk X: Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Tobacco (Smoked): May decrease the serum concentration of Tasimelteon. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Adverse events were observed in some animal reproduction studies.
It is not known if tasimelteon is excreted into breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
Avoid or limit ethanol.
Agonist of melatonin receptors MT1 and MT2 (greater affinity for the MT2 receptor than the MT1 receptor). Agonism of MT1 is thought to preferentially induce sleepiness, while MT2 receptor activation preferentially influences regulation of circadian rhythms.
Onset: Effect may take weeks or months (due to individual differences in circadian rhythms).
Absorption: Capsule: High-fat meals delayed Tmax and maximum serum concentration was reduced by 44%.
Protein binding: ~90%.
Distribution: Vd: ~59 to 126 L.
Metabolism: Hepatic (extensive); oxidative metabolism primarily through CYP1A2 and CYP3A4. Phenolic glucuronidation is the major phase II metabolic route.
Bioavailability: Capsule: ~38%.
Half-life elimination: ~1 to 2 hours.
Time to peak: Fasting: Capsule: ~0.5 to 3 hours (increased by ~1.75 hours with a high-fat meal); Suspension: 15 to 30 minutes.
Excretion: Urine (80%; <1% as unchanged drug); feces (~4%).
Altered kidney function: Patients with severe renal impairment (GFR <15 mL/minute/1.73 m2) had a 30% lower clearance compared to healthy patients; clearance in patients with end-stage renal disease was comparable to that of healthy subjects.
Hepatic function impairment: Tasimelteon exposure was increased less than 2-fold in patients with moderate hepatic impairment (Child-Pugh Score ≥7 and ≤9 points).
Older adult: In elderly subjects, tasimelteon exposure increased by ~2-fold compared with younger adults.
Sex: The mean overall exposure of tasimelteon was ~20% to 30% greater in female than in male subjects.
Cigarette smoking: Exposure decreased by ~40% in smokers, compared to nonsmokers.
Capsules (Hetlioz Oral)
20 mg (per each): $952.36
Suspension (Hetlioz LQ Oral)
4 mg/mL (per mL): $190.47
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