Hetlioz LQ tasimelteon 4 mg/mL Suspension
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Melatonin Receptor Agonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Tasimelteon is used to treat non-24-hour sleep-wake disorder (non-24; a condition that occurs mainly in people who are blind in which the body's natural clock is out of sync with the normal day-night cycle and causes a disrupted sleep schedule) in adults. It is also used to treat nighttime sleep problems in adults and children 3 years of age and older with Smith-Magenis Syndrome (SMS; a developmental disorder). Tasimelteon is in a class of medications called melatonin receptor agonists. It works similarly to melatonin, a natural substance in the brain that is needed for sleep.
Read the full MedlinePlus article ↗- That's a really common question, and the honest answer is: it varies. Because everyone's internal body clock runs a little differently, some people notice improvement within a few...
- How long will it take before I actually start sleeping better?
- You'll want to time your meal carefully. Eating — especially a high-fat meal — can significantly reduce how much tasimelteon your body actually absorbs, and it delays how quickly t...
- Drowsiness is a known effect of tasimelteon, which is actually intentional — it's helping shift your sleep timing. The main advice is to take it and then head straight to bed; don'...
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Supplement & herbal interactions
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $172.23 | $8,266.99 / 48 ml |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Hetlioz LQ 4 mg/mLthis 43068-0304-02 | Vanda | 1 bottle | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11141400 ↗ | Method of use | U-3007 | Oct 10, 2034 |
| US 10980770 ↗ | Method of use | U-3106 | Jan 25, 2033 |
| US 11266622 ↗ | Method of use | U-3003 | Aug 29, 2035 |
| US 11633377 ↗ | Method of use | U-3003 | Jan 25, 2033 |
| US 10149829 ↗ | Method of use | U-3006 | Jan 25, 2033 |
| US 9730910 ↗ | Method of use | U-3005 | May 17, 2034 |
| US 9539234 ↗ | Method of use | U-3004 | Jan 25, 2033 |
| US 10610510 ↗ | Method of use | U-3009 | Jan 25, 2033 |
| US 10376487 ↗ | Method of use | U-3007 | Jul 27, 2035 |
| US 10179119 ↗ | Method of use | U-3003 | Aug 29, 2035 |
| US 10610511 ↗ | Method of use | U-3007 | Oct 10, 2034 |
| US 12447141 ↗ | Method of use | U-3003 | Dec 11, 2040 |
| US 12201604 ↗ | Method of use | U-3003 | Jan 25, 2033 |
| US 11759446 ↗ | Method of use | U-3003 | Feb 21, 2041 |
| US 11786502 ↗ | Method of use | U-3007 | Oct 10, 2034 |
| US 11833130 ↗ | Method of use | U-3003 | Jan 25, 2033 |
| US 11850229 ↗ | Method of use | U-3342 | Jan 25, 2033 |
| US 11918556 ↗ | Method of use | U-3342 | Apr 7, 2033 |
| US 11826339 ↗ | Method of use | U-3342 | Jan 25, 2033 |
| US 11918557 ↗ | Method of use | U-3003 | Jan 25, 2033 |
| US 11285129 ↗ | Method of use | U-3342 | Jan 25, 2033 |
| US 12049457 ↗ | Drug substance | — | Feb 12, 2035 |
| US 10829465 ↗ | Drug substance | — | Feb 12, 2035 |
| US 10071977 ↗ | Drug substance | — | Feb 12, 2035 |
| US 11202770 ↗ | Drug product | — | Dec 11, 2040 |
| US 11566011 ↗ | Drug substance | — | Feb 12, 2035 |
| US 11760740 ↗ | Drug substance | — | Feb 12, 2035 |
| Code | What it grants | Expires |
|---|---|---|
| ODE-329 | Orphan Drug Exclusivity (7-year) | Dec 1, 2027 |
Is there a generic version of HETLIOZ LQ 4 MG/ML SUSPENSION?
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💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 43068-0304-02 You're viewing this | 1 BOTTLE in 1 CARTON (43068-304-02) / 48 mL in 1 BOTTLE | 2020-12-10 | Active |
| 43068-0304-06 | 1 BOTTLE in 1 CARTON (43068-304-06) / 158 mL in 1 BOTTLE | 2020-12-10 | Active |
Pack size FAQ
What quantity is in NDC 43068-0304-02?
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE HETLIOZ is a melatonin receptor agonist. HETLIOZ capsules are indicated for the treatment of: Non-24-Hour Sleep-Wake Disorder (Non-24) in adults ( 1 ) Nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) in patients 16 years of age and older ( 1 ) HETLIOZ LQ oral suspension is indicated for the treatment of: Nighttime sleep disturbances in SMS in pediatric patients 3 years to 15 years of age ( 1 )
1.1Non-24-Hour Sleep-Wake Disorder (Non-24) HETLIOZ capsules are indicated for the treatment of Non-24 in adults.
1.2Nighttime Sleep Disturbances in Smith-Magenis Syndrome (SMS) HETLIOZ capsules are indicated for the treatment of nighttime sleep disturbances in SMS in patients 16 years of age and older. HETLIOZ LQ oral suspension is indicated for the treatment of nighttime sleep disturbances in SMS in pediatric patients 3 to 15 years of age.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Indicated Population Dosage Form Body Weight Recommended Dosage Non-24 ( 2.2 ) Adults Capsules Not applicable 20 mg one hour prior to bedtime Nighttime sleep disturbances in SMS ( 2.3 ) Patients 16 years of age and older Capsules Not applicable 20 mg one hour prior to bedtime Pediatric Patients 3 to 15 years of age Oral Suspension ≤ 28 kg 0.7 mg/kg one hour before bedtime >28 kg 20 mg one hour before bedtime HETLIOZ capsules and HETLIOZ LQ oral suspension are not substitutable ( 2.1 ) Administer at the same time every night ( 2.2 , 2.3 ) Take without food ( 2.4 )
2.1Non-Interchangeability between HETLIOZ Capsules and HETLIOZ LQ Oral Suspension HETLIOZ capsules and HETLIOZ LQ oral suspension are not substitutable [see Clinical Pharmacology ( 12.3 )].
2.2Recommended Dosage for HETLIOZ Capsules for Non-24 Adults The recommended dosage of HETLIOZ capsules in adults is 20 mg one hour before bedtime, at the same time every night. Because of individual differences in circadian rhythms, drug effect may not occur for weeks or months.
2.3Recommended Dosage for HETLIOZ Capsules and HETLIOZ LQ Oral Suspension for Nighttime Sleep Disturbances in SMS Patients 16 years of Age and Older The recommended dosage of HETLIOZ capsules in patients 16 years and older is 20 mg one hour before bedtime, at the same time every night. Pediatric Patients 3 Years to 15 Years of Age The recommended dosage of HETLIOZ LQ oral suspension in pediatric patients 3 years to 15 years of age is based on body weight ( Table 1 ). Administer HETLIOZ one hour before bedtime, at the same time every night.
Table 1: Recommended Dosage of HETLIOZ LQ Oral Suspension for the Treatment of Nighttime Sleep Disturbances in SMS in Pediatric Patients 3 Years to 15 Years of Age Body Weight Daily Dose (oral suspension) ≤28 kg 0.7 mg/kg one hour before bedtime >28 kg 20 mg one hour before bedtime
2.4Important Administration Information Administer HETLIOZ capsules and HETLIOZ LQ oral suspension without food [see Clinical Pharmacology ( 12.3 )]. If a patient is unable to take HETLIOZ at approximately the same time on a given night, they should skip that dose and take the next dose as scheduled. HETLIOZ LQ Oral Suspension See " Instructions for Use " for complete administration instructions.
Shake HETLIOZ LQ oral suspension well for at least 30 seconds before every administration. Remove seal and insert press-in bottle adapter (included in the package) into the neck of the bottle until a tight seal is made. Turn the bottle upside down and withdraw the prescribed amount of HETLIOZ LQ oral suspension from the bottle.
Leave the press-in bottle adapter in place on bottle neck and replace cap on bottle. Store refrigerated. After opening, discard after 5 weeks (for the 48 mL bottle) and after 8 weeks (for the 158 mL bottle).
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Capsules: 20 mg size 1 dark blue opaque, hard gelatin capsules printed with “VANDA 20 mg” in white. Oral suspension: 4 mg/mL white to slightly yellow opaque suspension in 48 mL or 158 mL bottles. Capsules: 20 mg ( 3 ) Oral suspension: 4 mg/mL ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS May cause somnolence: After taking HETLIOZ, patients should limit their activity to preparing for going to bed, because HETLIOZ can impair the performance of activities requiring complete mental alertness ( 5.1 )
5.1Somnolence After taking HETLIOZ, patients should limit their activity to preparing for going to bed. HETLIOZ can potentially impair the performance of activities requiring complete mental alertness.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The most common adverse reactions (incidence >5% and at least twice as high on HETLIOZ than on placebo) were headache, increased alanine aminotransferase, nightmares or unusual dreams, and upper respiratory or urinary tract infection ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vanda Pharmaceuticals Inc. at 1-844-438-5469 or www.hetlioz.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. More than 2080 subjects have been treated with at least one dose of HETLIOZ, of which more than 380 have been treated for > 26 weeks and more than 170 have been treated for > 1 year. Non-24-Hour Sleep-Wake Disorder (Non-24) A 26-week, parallel-arm placebo-controlled study (Study 1) evaluated HETLIOZ (n=42) compared to placebo (n=42) in patients with Non-24.
A randomized-withdrawal, placebo- controlled study of 8 weeks duration (Study 2) also evaluated HETLIOZ (n=10), compared to placebo (n=10), in patients with Non-24. In placebo-controlled studies, 6% of patients exposed to HETLIOZ discontinued treatment due to an adverse event, compared with 4% of patients who received placebo. Table 2 shows the incidence of adverse reactions from Study 1. *Adverse reactions with an incidence > 5% and at least twice as high on HETLIOZ than on placebo are displayed.
Table 2: Adverse Reactions in Study 1 HETLIOZ N=42 Placebo N=42 Headache 17 % 7 % Alanine aminotransferase increased 10 % 5 % Nightmare/abnormal dreams 10 % 0 % Upper respiratory tract infection 7 % 0 % Urinary tract infection 7 % 2 % Nighttime Sleep Disturbances in Smith-Magenis Syndrome (SMS) A 9-week, double-blind, randomized, placebo-controlled, two-period crossover study evaluated HETLIOZ (capsules and oral suspension; n=25) compared to placebo (n=26) in the treatment of nighttime sleep disturbances in patients with Smith-Magenis Syndrome.
Pediatric patients (n=11, age 3 to 15 years) received HETLIOZ LQ oral suspension, and patients ≥16 years of age (n=14) received HETLIOZ capsules. Adverse reactions were similar in patients treated for Non-24 and patients with Smith-Magenis syndrome treated for nighttime sleep disturbances. Adverse reactions were also similar in pediatric patients (3 years to 15 years) who received HETLIOZ LQ oral suspension, and patients ≥16 years of age who received HETLIOZ capsules.
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Strong CYP1A2 inhibitors (e.g., fluvoxamine): Avoid use of HETLIOZ in combination with strong CYP1A2 inhibitors because of increased exposure ( 7.1 , 12.3 ) Strong CYP3A4 inducers (e.g., rifampin): Avoid use of HETLIOZ in combination with rifampin or other CYP3A4 inducers, because of decreased exposure ( 7.2 , 12.3 )
7.1Strong CYP1A2 Inhibitors (e.g., fluvoxamine) Avoid use of HETLIOZ in combination with fluvoxamine or other strong CYP1A2 inhibitors because of a potentially large increase in tasimelteon exposure and greater risk of adverse reactions [see Clinical Pharmacology ( 12.3 )].
7.2Strong CYP3A4 Inducers (e.g., rifampin) Avoid use of HETLIOZ in combination with rifampin or other CYP3A4 inducers because of a potentially large decrease in tasimelteon exposure with reduced efficacy [see Clinical Pharmacology ( 12.3 )].
7.3Beta-adrenergic Receptor Antagonists (e.g., acebutolol, metoprolol) Beta-adrenergic receptor antagonists have been shown to reduce the production of melatonin via specific inhibition of beta-1 adrenergic receptors. Nighttime administration of beta-adrenergic receptor antagonists may reduce the efficacy of HETLIOZ.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Hepatic impairment : HETLIOZ has not been studied in patients with severe hepatic impairment and is not recommended in these patients ( 8.6 )
8.1Pregnancy Risk Summary Available postmarketing case reports with HETLIOZ use in pregnant women are not sufficient to evaluate drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In pregnant rats, no embryofetal developmental toxicity was observed at exposures of 50 mg/kg/day, or up to 24 times higher than the human exposure at the maximum recommended human dose (MRHD) (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In pregnant rats administered tasimelteon at oral doses of 5, 50, or 500 mg/kg/day during the period of organogenesis, there were no effects on embryofetal development. The highest dose tested is approximately 240 times the MRHD of 20 mg/day, based on mg/m 2 body surface area.
In pregnant rabbits administered tasimelteon at oral doses of 5, 30, or 200 mg/kg/day during the period of organogenesis, embryolethality and embryofetal toxicity (reduced fetal body weight and delayed ossification) were observed at the highest dose tested. The highest dose is approximately 200 times the MRHD. Oral administration of tasimelteon at 50, 150, or 450 mg/kg/day to rats throughout organogenesis resulted in persistent reductions in body weight, delayed sexual maturation, and physical development, and neurobehavioral impairment in offspring at the highest dose tested which is approximately 220 times the MRHD based on mg/m2 body surface area.
Reduced body weight in offspring was also observed at the mid-dose. The no effect dose (NOEL), (50 mg/kg/day) is approximately 25 times the MRHD based on mg/m 2 body surface area.
8.2Lactation Risk Summary There are no data on the presence of tasimelteon or its metabolites in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for HETLIOZ and any potential adverse effects on the breastfed infant from HETLIOZ or from the underlying maternal condition.
8.4Pediatric Use Safety and effectiveness of HETLIOZ for the treatment of Non-24 in pediatric patients have not been established. Safety and effectiveness of HETLIOZ LQ oral suspension for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) have been established in pediatric patients 3 years and older. Use is based on a placebo-controlled crossover study of pediatric and adult patients [see Clinical Studies ( 14.2 )].
Safety and effectiveness of HETLIOZ for the treatment of nighttime sleep disturbances in SMS have not been established in patients younger than 3 years old. Juvenile Animal Toxicity Data Juvenile rats received oral doses of tasimelteon at 50, 150, or 450 mg/kg from weaning (day 21) through adulthood (day 90). These doses are approximately 12 to 108 times the maximum recommended human dose (MRHD) of 20 mg based on a mg/m 2 body surface area.
Toxicity was observed mainly at the highest dose and included mortality (females only), tremors, unsteady gait, decrease in growth and development compared to controls. The former reflected as decreases in bone growth, bone mineral content, bone ossification, and a delay in attainment of sexual maturation. Tasimelteon had no effect on fertility, reproduction, or learning and memory.
The No Observed Adverse Effect Level (NOAEL) is 150 mg/kg/day, which is approximately 178 times the MRHD based on AUC.
8.5Geriatric Use The risk of adverse reactions may be greater in elderly (>65 years) patients than younger patients because exposure to ta…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Available postmarketing case reports with HETLIOZ use in pregnant women are not sufficient to evaluate drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In pregnant rats, no embryofetal developmental toxicity was observed at exposures of 50 mg/kg/day, or up to 24 times higher than the human exposure at the maximum recommended human dose (MRHD) (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In pregnant rats administered tasimelteon at oral doses of 5, 50, or 500 mg/kg/day during the period of organogenesis, there were no effects on embryofetal development. The highest dose tested is approximately 240 times the MRHD of 20 mg/day, based on mg/m 2 body surface area.
In pregnant rabbits administered tasimelteon at oral doses of 5, 30, or 200 mg/kg/day during the period of organogenesis, embryolethality and embryofetal toxicity (reduced fetal body weight and delayed ossification) were observed at the highest dose tested. The highest dose is approximately 200 times the MRHD. Oral administration of tasimelteon at 50, 150, or 450 mg/kg/day to rats throughout organogenesis resulted in persistent reductions in body weight, delayed sexual maturation, and physical development, and neurobehavioral impairment in offspring at the highest dose tested which is approximately 220 times the MRHD based on mg/m2 body surface area.
Reduced body weight in offspring was also observed at the mid-dose. The no effect dose (NOEL), (50 mg/kg/day) is approximately 25 times the MRHD based on mg/m 2 body surface area.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of HETLIOZ for the treatment of Non-24 in pediatric patients have not been established. Safety and effectiveness of HETLIOZ LQ oral suspension for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) have been established in pediatric patients 3 years and older. Use is based on a placebo-controlled crossover study of pediatric and adult patients [see Clinical Studies ( 14.2 )].
Safety and effectiveness of HETLIOZ for the treatment of nighttime sleep disturbances in SMS have not been established in patients younger than 3 years old. Juvenile Animal Toxicity Data Juvenile rats received oral doses of tasimelteon at 50, 150, or 450 mg/kg from weaning (day 21) through adulthood (day 90). These doses are approximately 12 to 108 times the maximum recommended human dose (MRHD) of 20 mg based on a mg/m 2 body surface area.
Toxicity was observed mainly at the highest dose and included mortality (females only), tremors, unsteady gait, decrease in growth and development compared to controls. The former reflected as decreases in bone growth, bone mineral content, bone ossification, and a delay in attainment of sexual maturation. Tasimelteon had no effect on fertility, reproduction, or learning and memory.
The No Observed Adverse Effect Level (NOAEL) is 150 mg/kg/day, which is approximately 178 times the MRHD based on AUC.
🧓 Geriatric Use ▾
8.5Geriatric Use The risk of adverse reactions may be greater in elderly (>65 years) patients than younger patients because exposure to tasimelteon is increased by approximately 2-fold compared with younger patients.
🆘 Overdosage ▾
10 OVERDOSAGE There is limited premarketing clinical experience with the effects of an overdosage of HETLIOZ. As with the management of any overdose, general symptomatic and supportive measures should be used, along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed.
Respiration, pulse, blood pressure, and other appropriate vital signs should be monitored, and general supportive measures employed. While hemodialysis was effective at clearing HETLIOZ and the majority of its major metabolites in patients with renal impairment, it is not known if hemodialysis will effectively reduce exposure in the case of overdose. As with the management of any overdose, the possibility of multiple drug ingestion should be considered.
Contact a poison control center for current information on the management of overdose.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism by which tasimelteon exerts its therapeutic effect in patients with Non-24 or nighttime sleep disturbances in SMS is unclear. However, tasimelteon is an agonist at melatonin MT 1 and MT 2 receptors which are thought to be involved in the control of circadian rhythms.
12.2Pharmacodynamics Tasimelteon is an agonist at MT 1 and MT 2 receptors with greater affinity for the MT 2 as compared to the MT 1 receptor (Ki = 0.304 nM and 0.07 nM, respectively). The major metabolites of tasimelteon have less than one-tenth of the binding affinity of the parent molecule for both the MT 1 and MT 2 receptors.
12.3Pharmacokinetics The pharmacokinetics of tasimelteon is linear over doses ranging from 3 to 300 mg (0.15 to 15 times the recommended daily dosage). The pharmacokinetics of tasimelteon and its metabolites did not change with repeated daily dosing. Absorption The absolute oral bioavailability is 38.3%.
The peak concentration (T max ) of tasimelteon capsule occurred approximately 0.5 to 3 hours after fasted oral administration. The Tmax of tasimelteon suspension occurred approximately 15 to 30 minutes after fasted oral administration. The pharmacokinetic profile of oral suspension has not been directly compared to capsules; therefore, capsules are the only dosage form recommended for use in adults.
Effect of food When administered with a high-fat meal, the Cmax of tasimelteon was 44% lower than when given in a fasted state, and the median Tmax was delayed by approximately 1.75 hours. Therefore, HETLIOZ should be taken without food. Distribution The apparent oral volume of distribution of tasimelteon at steady state in young healthy subjects is approximately 59 - 126 L.
At therapeutic concentrations, tasimelteon is about 90% bound to proteins. Metabolism Tasimelteon is extensively metabolized. Metabolism of tasimelteon consists primarily of oxidation at multiple sites and oxidative dealkylation resulting in opening of the dihydrofuran ring followed by further oxidation to give a carboxylic acid.
CYP1A2 and CYP3A4 are the major isozymes involved in the metabolism of tasimelteon. Phenolic glucuronidation is the major phase II metabolic route. Major metabolites had 13-fold or less activity at melatonin receptors compared to tasimelteon.
Elimination Following oral administration of radiolabeled tasimelteon, 80% of total radioactivity was excreted in urine and approximately 4% in feces, resulting in a mean recovery of 84%. Less than 1% of the dose was excreted in urine as the parent compound. The observed mean elimination half-life for tasimelteon is 1.3 ± 0.4 hours.
The mean terminal elimination half-life ± standard deviation of the main metabolites ranges from 1.3 ± 0.5 to 3.7 ± 2.2. Repeated once daily dosing with HETLIOZ does not result in changes in pharmacokinetic parameters or significant accumulation of tasimelteon. Studies in Specific Populations Elderly In elderly subjects, tasimelteon exposure increased by approximately two-fold compared with non-elderly adults.
Pediatric Patients Pharmacokinetic information in pediatric patients are available only for the oral suspension formulation. Body weight was found to have significant effect on the pharmacokinetics. The increase in body weight was associated with increase in tasimelteon clearance up to 28 kg.
The average dose normalized Cmax and AUC inf at the recommended dose was 231 ng/mL and 310 ng.h/mL. No data are available in patients less than 3 years old. Gender The mean overall exposure of tasimelteon was approximately 20-30% greater in female than in male subjects.
Race The effect of race on exposure of HETLIOZ was not evaluated. Hepatic Impairment The pharmacokinetic profile of a 20 mg dose of HETLIOZ was compared among eight subjects with mild hepatic impairment (Child-Pugh Score ≥5 and ≤6 points), eight subjects with moderate hepatic impairment (Child-Pugh Score ≥7 and ≤9 points), and 13 healthy matched controls.…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism by which tasimelteon exerts its therapeutic effect in patients with Non-24 or nighttime sleep disturbances in SMS is unclear. However, tasimelteon is an agonist at melatonin MT 1 and MT 2 receptors which are thought to be involved in the control of circadian rhythms.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING HETLIOZ Capsules 20 mg capsules are available as size 1, dark blue opaque, hard gelatin capsules printed with “VANDA 20 mg” in white, containing 20 mg of tasimelteon per capsule. NDC 43068-220-01 Bottles of 30 capsules NDC 43068-220-02 Blister Pack containing 3 capsules HETLIOZ LQ Oral Suspension 4 mg/mL white to slightly yellow opaque suspension. Each bottle has a child resistant cap and packaged in a carton.
Each carton contains a bottle of HETLIOZ LQ oral suspension, a 5 mL oral dosing syringe and a press-in bottle adapter. NDC 43068-304-02 Bottles of 48 mL NDC 43068-304-06 Bottles of 158 mL Storage and Handling HETLIOZ Capsules Store HETLIOZ capsules at controlled room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Protect from exposure to light and moisture.
HETLIOZ LQ Oral Suspension Store HETLIOZ LQ oral suspension at refrigerated temperature 5°C (41°F); excursions permitted to 2°C to 8°C (36°F t o 46°F).
📦 Storage and Handling ▾
Storage and Handling HETLIOZ Capsules Store HETLIOZ capsules at controlled room temperature, 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Protect from exposure to light and moisture. HETLIOZ LQ Oral Suspension Store HETLIOZ LQ oral suspension at refrigerated temperature 5°C (41°F); excursions permitted to 2°C to 8°C (36°F t o 46°F).
📋 Description ▾
11 DESCRIPTION HETLIOZ contains tasimelteon, a melatonin receptor agonist, chemically designated as (1 R , 2 R )-N-[2- (2,3-dihydrobenzofuran-4-yl)cyclopropylmethyl]propanamide, containing two chiral centers. The molecular formula is C 15 H 19 NO 2 , and the molecular weight is 245.32. The structural formula is: Tasimelteon is a white to off-white crystalline powder. It is very slightly soluble in cyclohexane, slightly soluble in water and
0.1N hydrochloric acid, and freely soluble or very soluble in methanol, 95% ethanol, acetonitrile, isopropanol, polyethylene glycol 300, propylene glycol and ethyl acetate. HETLIOZ capsules are intended for oral administration. Each capsule contains 20 mg of tasimelteon and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose anhydrous, magnesium stearate, and microcrystalline cellulose.
Each hard gelatin capsule consists of FD&C Blue #1, FD&C Red #3, and FD&C Yellow #6, gelatin, and titanium dioxide. HETLIOZ LQ oral suspension contains 4 mg of tasimelteon per mL of suspension and the following inactive ingredients: ascorbic acid, cherry flavor, mannitol, microcrystalline cellulose/carboxymethylcellulose sodium, polysorbate 80, sodium benzoate, sodium chloride, sucrose, sucralose, and water. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling for HETLIOZ LQ oral suspension, if appropriate ( Instructions for Use ). Advise patients to limit their activities to preparing for going to bed after taking HETLIOZ capsules or HETLIOZ LQ oral suspension because HETLIOZ can potentially impair the performance of activities requiring complete mental alertness [see Warnings and Precautions ( 5.1 )]. Administration Information for HETLIOZ capsules and HETLIOZ LQ oral suspension [see Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.4 )] .
Advise patients to take HETLIOZ without food. Advise patients to take HETLIOZ before bedtime at the same time every night. Advise patients to skip the dose that night if they cannot take HETLIOZ at approximately the same time on a given night.
Advise patients to swallow HETLIOZ capsules whole. HETLIOZ LQ oral suspension: Advise patients to shake the bottle for at least 30 seconds before each administration; use the press-in bottle adapter included in the package; leave the adapter in place on the bottle neck; replace the cap; and refrigerate after each use. After opening, discard after 5 weeks (for the 48 mL bottle) and after 8 weeks (for the 158 mL bottle).
Non-24 (HETLIOZ capsules) Advise patients that because of individual differences in circadian rhythms, daily use for several weeks or months may be necessary before benefit from HETLIOZ is observed [see Dosage and Administration ( 2.2 )] . Distributed by: Vanda Pharmaceuticals Inc. Washington, D.C.
20037 USA www.hetlioz.com Vanda, HETLIOZ, and HETLIOZ LQ are registered trademarks of Vanda Pharmaceuticals Inc. in the United States and other countries.