1) ADVERSE EFFECTS: Elevated alanine aminotransferase, headache, nightmares or abnormal dreams, somnolence, upper respiratory tract infection, and urinary tract infection have been reported.

1) Toxicity following overdose has not been reported. Overdose effects are anticipated to be an extension of adverse effects following therapeutic doses.

1) Treatment is symptomatic and supportive.

1) Treatment is symptomatic and supportive.

1) PREHOSPITAL: Prehospital gastrointestinal decontamination is generally not necessary.
2) HOSPITAL: Gastrointestinal decontamination is generally not necessary. Consider activated charcoal following a recent significant exposure or if a more toxic coingestant is involved; administer activated charcoal if the patient is not vomiting, and the airway is protected.

1) Monitor respiratory and CNS function. Assess airway and pulse oximetry following a significant exposure. Although not anticipated to be necessary following a minor or moderate exposure, ensure adequate ventilation and perform endotracheal intubation in patients as necessary.

1) None.

1) Tasimelteon is highly protein bound (90%) and has a large volume of distribution (56 to 126 L); therefore, hemodialysis is UNLIKELY to be effective.

1) HOME CRITERIA: Most inadvertent ingestions can be managed at home.
2) OBSERVATION CRITERIA: All patients with deliberate self-harm ingestions and any symptomatic patients should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions should be evaluated in a healthcare facility.
3) ADMISSION CRITERIA: Patients who remain symptomatic despite treatment should be admitted.
4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.

1) Consider the possibility of multidrug involvement when managing a suspected overdose.

1) Tasimelteon displays linear pharmacokinetics over doses ranging from 3 to 300 mg. Peak concentration occurs within 0.5 to 3 hours following fasting administration of oral tasimelteon. Significant decreases and delays in absorption of tasimelteon are noted when this medication is taken concurrently with a fatty meal. In the body, tasimelteon is 90% protein bound and has a volume of distribution of 56 to 126 L. Tasimelteon is extensively metabolized via CYP1A2 and CYP3A4. Metabolism consists primarily of oxidation at multiple sites and oxidative dealkylation opens the dihydrofuran ring; further oxidation yields a carboxylic acid. A phase 2 metabolic route primarily involve phenolic glucuronidation. Elimination is mostly via the urine. Following radiolabeled dosing, 80% was recovered in urine primarily as metabolites and 4% was recovered in feces. The mean elimination half-life is 1.3 hours.

1) Other chemicals or drugs that may produce somnolence or a decrease in CNS function.

1) WITH POISONING/EXPOSURE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) LACK OF EFFECT
2) EMBRYOLETHALITY AND EMBRYOFETAL TOXICITY

1) Tasimelteon is classified as FDA Pregnancy Category C (Prod Info HETLIOZ(TM) oral capsules, 2014).

1) RATS: During animal studies, oral doses of tasimelteon 450 mg/kg/day given to rats throughout organogenesis and lactation resulted in persistent reductions in body weight, delayed sexual maturation and physical development, and neurobehavioral impairment in offspring. Reduced body weight was also observed in offspring following an oral dose of 150 mg/kg/day, but no effect was seen with administration of 50 mg/kg/day (approximately 25 times the RHD on a mg/m(2) basis) (Prod Info HETLIOZ(TM) oral capsules, 2014).
2) RABBITS: During animal studies, reduced body weight was observed in pregnant rabbits that received oral tasimelteon 200 mg/kg/day during organogenesis, although no adverse effects were seen at doses up to 30 mg/kg/day (approximately 30 times the RHD on a mg/m(2) basis) (Prod Info HETLIOZ(TM) oral capsules, 2014).

1) It is unknown whether tasimelteon is excreted in human breast milk (Prod Info HETLIOZ(TM) oral capsules, 2014).

1) RATS: Estrus cycle disruption and decreased fertility were observed in male and female rats exposed to tasimelteon 50 and 500 mg/kg/day prior to and throughout mating and continuing in females to gestation day 7. The no-effect dose for female reproductive effects was 5 mg/kg/day (approximately twice the recommended human dose on a mg/m(2) basis) (Prod Info HETLIOZ(TM) oral capsules, 2014).

1) RATS: An increased incidence in the development of liver tumors was observed in rats administered oral tasimelteon for up to 2 years at doses of 100 and 250 mg/kg/day. Liver tumors observed in male rats included adenoma and carcinoma; adenoma was observed in female rats (Prod Info HETLIOZ(TM) oral capsules, 2014).

1) RATS: The incidence of uterine (endometrial adenocarcinoma) and cervical (squamous cell carcinoma) tumors increased in rats administered oral tasimelteon 250 mg/kg/day for up to 2 years (Prod Info HETLIOZ(TM) oral capsules, 2014).

1) MICE: No evidence of carcinogenic potential was observed in mice administered oral tasimelteon for up to 2 years at doses up to 300 mg/kg/day (approximately 75 times the recommended human dose (RHD) of 20 mg/day on a mg/m(2) basis) (Prod Info HETLIOZ(TM) oral capsules, 2014).
2) RATS: No evidence of increased tumor incidence was observed in rats administered oral tasimelteon 20 mg/kg/day for up to 2 years (approximately 10 times the RHD of 20 mg/day on a mg/m(2) basis) (Prod Info HETLIOZ(TM) oral capsules, 2014).

1) Routine laboratory studies are not needed unless otherwise clinically indicated.
2) Monitor liver enzymes in cases of a very large exposure.
3) Plasma concentrations are not readily available or clinically useful in the management of overdose.

A) Patients who remain symptomatic despite treatment should be admitted.

A) Most inadvertent ingestions can be managed at home.

A) Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.

A) All patients with deliberate self-harm ingestions and any symptomatic patients should be evaluated in a healthcare facility and monitored until symptoms resolve. Children with unintentional ingestions should be evaluated in a healthcare facility.

1) CHARCOAL ADMINISTRATION
2) CHARCOAL DOSE

1) MANAGEMENT OF MILD TO MODERATE TOXICITY
2) MANAGEMENT OF SEVERE TOXICITY

1) Monitor vitals signs and mental status. Assess respiratory function and airway.
2) Routine laboratory studies are not needed unless otherwise clinically indicated.
3) Monitor liver enzymes in cases of very large exposure.
4) Plasma concentrations are not readily available or clinically useful in the management of overdose.