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Tasimelteon 20 mg Capsule, 30-count — NDC 60505-4665-03 package photo

Tasimelteon 20 mg Capsule, 30-count

by Apotex Corp. · 30 CAPSULE in 1 BOTTLE (60505-4665-3)
NDC 60505-4665-03
🏷️ FDA NDC (as labeled) 60505-4665-3 billing pads the package segment with a zero
This package
Contains30-count Cost per ea$271.22 NADAC Per package$8,136.63 / 30 capsules Pack sizes2 compare ↓
Also priced by: Medicaid pays $435.85/unit · Part D plans $560.94/unit — full pricing hub ↓
Also comes in: 90 capsules 60505-4665-09
Rx only Generic On market Non-controlled
🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

🆔 Identity & classification

FDA NDC (as labeled) 60505-4665-3
Product NDC 60505-4665
11-digit billing NDC 60505466503
NCPDP billing unit EA — each (per item)
RxCUI 1490473
UNII SHS4PU80D9
UPC 0360505466535
Application # ANDA211607
SPL Set ID 46b09064-a675-92d5-24a7-dac0410f77ae
Established class (EPC) Melatonin Receptor Agonist
Mechanism of action Melatonin Receptor Agonists
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2024-01-05
Route ORAL
Dosage form CAPSULE
Substance TASIMELTEON
GPI-14 60250070000130
GCN Seq No 072007
GCN 36068
HICL code 040927
Ingredient (HICL) Tasimelteon
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H8
Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 2)
HIC3 code H8B
Therapeutic class — specific (HIC3) Hypnotics, Melatonin Mt1/Mt2 Receptor Agonists
AHFS code 28:24.48.00
AHFS class Melatonin Receptor Agonists
FDB label name TASIMELTEON 20 MG CAPSULE
FDB brand name Tasimelteon
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 60505-4665-3 — a 5-4-1 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the package segment → 60505-4665-03. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the Melatonin Receptor Agonist class.

Pharmacologic class Melatonin Receptor Agonist
Drug family (ATC) Melatonin receptor agonists
How it works Melatonin Receptor Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerApotex Corp.
Application holderAPOTEX INC
FDA applicationANDA211607 (ANDA)
Labeler code60505
First marketedJan 2024
Product typeHuman Prescription Drug
Portfolio306 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name TASIMELTEON 20 MG CAPSULE Ingredient Tasimelteon
📖 What it is MedlinePlus · NLM

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 ↗
📗 Our plain-language guide HelloPharmacist
  • 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'...
📖 Read our full Tasimelteon guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color Blue
ShapeCapsule
ImprintAPO;TAS;20
Size14 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 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.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII H3R47K3TBD
    FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
  • UNII PN2ZH5LOQY
    A synthetic red dye approved by the FDA for use in foods, medicines, and cosmetics. It serves as a colorant to make tablets, capsules, and liquids visually distinctive for product identification.
  • UNII H77VEI93A8
    A synthetic yellow dye used to color medications. It helps identify the drug and make it visually distinctive, with no effect on how the medicine works.
  • UNII 2G86QN327L
    Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII FZ989GH94E
    Povidone is a synthetic polymer made from a plastic-like material. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in your stomach so the medicine can be absorbed.
  • UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • UNII 46N107B71O
    Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • UNII 15FIX9V2JP
    Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.

13 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMedingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 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 systemPer eaPer package
Retail pharmacies payNADAC · weekly $271.221 $8,136.63 / 30 capsules
Medicaid paysCMS SDUD · 12 mo $435.85 $13,075.53 / 30 capsules
Medicare drug plans payPart D · Q2 2026 $560.94 $16,828.19 / 30 capsules
NADAC price history (per ea) — tap or hover for the price & month
Dec 2025 Feb 2026 May 2026 Aug 2026 $403.870 $271.221
▼ Down 31% over the last 9 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Tasimelteon 20 mg 00480-4490-56 Teva 30 capsules $271.221 AB Availability likely
Tasimelteon 20 mgthis 60505-4665-03 Apotex 30 capsules $271.221 AB Availability likely
Tasimelteon 20 mg 69238-2548-03 Amneal 30 capsules $271.221 AB Availability likely
Hetlioz 20 mg 43068-0220-01 Vanda 30 capsules AB FDA listed
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2024
On the market since
Jan 2024
📍
2026
Currently FDA-listed
2 years listed
🔓
·
Generic on the market
this product is a generic
This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 60505-4665-03, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
437
Units reimbursed last 4 qtrs
14.3K
Gross reimbursed last 4 qtrs
$6.23M
Avg / prescription
$14,258.41
Avg / unit
$435.85
Latest quarter Q1 2026
152Rx
Medicaid pays / ea
$435.85
gross reimbursed
vs
NADAC / ea
$271.22
acquisition cost
=
Spread
+$164.63
+61% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care
100% FFS
Fee-for-service · 437 Rx Managed care · 0 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: 8,024 units · 79.9 per 100k residents MI New York: 2,250 units · 11.5 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 4,022 units · 10.3 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
10.379.9
gray = no data reported
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Michigan 79.9 /100k
2 New York 11.5 /100k
3 California 10.3 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
30 capsules this page60505-4665-03 437 Rx · $6,230,927
90 capsules60505-4665-09 No Medicaid data
Drug total (last 4 qtrs): 437 Rx · 14,296 units · $6,230,927 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Tasimelteon — the program that covers self-administered drugs. 3 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Tasimelteon. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$11.28M
Claims incl. refills
672
Beneficiaries
294
Spend / beneficiary
$38,374.41
Spend / claim
$16,788.80
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Tasimelteon — the ingredient across all brands.

Top reported reactions

Insomnia728
Middle Insomnia414
Somnolence408
Headache386
Nightmare268
Abnormal Dreams223
Fatigue222

Age at onset

Adolescent6
Adult944
Elderly167

Reporter sex

5,770 reports
Male · 43%
Female · 57%

Serious outcomes

Death166
Disabling3
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 776 8
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startStatus
60505-4665-03 You're viewing this 30 CAPSULE in 1 BOTTLE (60505-4665-3) $271.22 / ea $8,136.63 2024-01-05 Active
60505-4665-09 90 CAPSULE in 1 BOTTLE (60505-4665-9) 2024-01-05 Active

You're viewing the smallest of 2 pack sizes for this product.

In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in NDC 60505-4665-03?
NDC 60505-4665-03 is a 30-count package — 30 capsule in 1 bottle.
What is the difference between NDC 60505-4665-03 and NDC 60505-4665-09?
Both are Tasimelteon 20 mg Capsule — the drug itself is identical. NDC 60505-4665-03 is the 30-count package, while NDC 60505-4665-09 is the 90 capsules package.
What NDC number is used to bill for this package of Tasimelteon 20 mg Capsule?
Bill NDC 60505-4665-03 — the 11-digit billing format is 60505466503. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage 45 words

1 INDICATIONS AND USAGE Tasimelteon capsules are a melatonin receptor agonist. Tasimelteon capsules are indicated for the treatment of Non ­24-Hour Sleep-Wake Disorder (Non-24) in adults ( 1 )

1.1Non-24-Hour Sleep-Wake Disorder (Non-24) Tasimelteon capsules are indicated for the treatment of Non-24 in adults.

⏱️ Dosage and Administration 170 words

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 Tasimelteon capsules and tasimelteon oral suspension are not substitutable ( 2.1 ) Administer at the same time every night ( 2.2 ) Take without food ( 2.4 )

2.1Non-Interchangeability between Tasimelteon Capsules and Tasimelteon Oral Suspension Tasimelteon capsules and tasimelteon oral suspension are not substitutable [see Clinical Pharmacology ( 12.3 )].

2.2Recommended Dosage for Tasimelteon Capsules for Non-24 Adults The recommended dosage of tasimelteon 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.

2.4Important Administration Information Administer tasimelteon capsules without food [see Clinical Pharmacology ( 12.3 )]. If a patient is unable to take tasimelteon capsules at approximately the same time on a given night, they should skip that dose and take the next dose as scheduled.

💊 Dosage Forms and Strengths 36 words

3 DOSAGE FORMS AND STRENGTHS Capsules: 20 mg hard gelatin capsule with dark blue, opaque body and dark blue, opaque cap. Imprinted “APO” and “TAS” over “20” in white ink. Capsules: 20 mg ( 3 )

Contraindications 7 words

4 CONTRAINDICATIONS None. None ( 4 )

⚠️ Warnings and Cautions 68 words

5 WARNINGS AND PRECAUTIONS May cause somnolence: After taking tasimelteon capsules, patients should limit their activity to preparing for going to bed, because tasimelteon capsules can impair the performance of activities requiring complete mental alertness ( 5.1 )

5.1Somnolence After taking tasimelteon capsules, patients should limit their activity to preparing for going to bed. Tasimelteon capsules can potentially impair the performance of activities requiring complete mental alertness.

🤒 Adverse Reactions ~1 min read

6 ADVERSE REACTIONS The most common adverse reactions (incidence >5% and at least twice as high on tasimelteon 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 Apotex Corp. at 1-800-706-5575 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 tasimelteon, 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 tasimelteon (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 tasimelteon (n=10), compared to placebo (n=10), in patients with Non-24. In placebo-controlled studies, 6% of patients exposed to tasimelteon 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.

Table 2: Adverse Reactions in Study 1 Tasimelteon 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 % *Adverse reactions with an incidence > 5% and at least twice as high on tasimelteon than on placebo are displayed.

🔄 Drug Interactions 167 words

7 DRUG INTERACTIONS Strong CYP1A2 inhibitors (e.g., fluvoxamine): Avoid use of tasimelteon in combination with strong CYP1A2 inhibitors because of increased exposure ( 7.1 , 12.3 ) Strong CYP3A4 inducers (e.g., rifampin): Avoid use of tasimelteon 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 tasimelteon 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 tasimelteon 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 tasimelteon.

👥 Use in Specific Populations ~3 min read

8 USE IN SPECIFIC POPULATIONS Hepatic impairment: Tasimelteon 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 tasimelteon 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/m 2 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 tasimelteon and any potential adverse effects on the breastfed infant from tasimelteon or from the underlying maternal condition.

8.4Pediatric Use Safety and effectiveness of tasimelteon capsules for the treatment of Non-24 in pediatric patients have not been established. 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 tasimelteon is increased by approximately 2-fold compared with younger patients.

8.6Hepatic Impairment Dose adjustment is not necessary in patients with mild or moderate hepatic impairment. Tasimelteon has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). Therefore, tasimelteon is not recommended for use in patients with severe hepatic impairment [see Clinical Pharmacology ( 12.3 )].

8.7 Smokers Smoking causes in…

🤰 Pregnancy ~1 min read

8.1Pregnancy Risk Summary Available postmarketing case reports with tasimelteon 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/m 2 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 147 words

8.4Pediatric Use Safety and effectiveness of tasimelteon capsules for the treatment of Non-24 in pediatric patients have not been established. 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 32 words

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 125 words

10 OVERDOSAGE There is limited premarketing clinical experience with the effects of an overdosage of tasimelteon. 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 tasimelteon 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 ~3 min read

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism by which tasimelteon exerts its therapeutic effect in patients with Non­-24 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. Effect of food When administered with a high-fat meal, the C max of tasimelteon was 44% lower than when given in a fasted state, and the median T max was delayed by approximately 1.75 hours. Therefore, tasimelteon capsules should be taken without food.

Distribution The apparent oral volume of distribution of tasimelteon at steady state in young healthy subjects is approximately 59 to 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 tasimelteon 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. Gender The mean overall exposure of tasimelteon was approximately 20 to 30% greater in female than in male subjects. Race The effect of race on exposure of tasimelteon was not evaluated.

Hepatic Impairment The pharmacokinetic profile of a 20 mg dose of tasimelteon 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. Tasimelteon exposure was increased less than two-fold in subjects with moderate hepatic impairment. Therefore, no dose adjustment is needed in patients with mild or moderate hepatic impairment.

Tasimelteon has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and is not recommended in these patients. Renal Impairment The pharmacokinetic profile of a 20 mg dose of tasimelteon was compared among eight subjects with severe renal impairment (estimated glomerular filtration rate [eGFR] ≤ 29 mL/min/1.73m 2 ), eight subjects with end-stage renal disease (ESRD) (GFR < 15 mL/min/1.73m 2 ) requiring hemodialysis, and sixteen healthy matched controls. There was no apparent relationship between tasimelteon…

🧬 Mechanism of Action 44 words

12.1Mechanism of Action The mechanism by which tasimelteon exerts its therapeutic effect in patients with Non­-24 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 78 words

16 HOW SUPPLIED/STORAGE AND HANDLING Tasimelteon 20 mg capsules are available as hard gelatin capsules with dark blue, opaque body and dark blue, opaque cap. Imprinted “APO” and “TAS” over “20” in white ink. Bottles of 30 NDC 60505-4665-3 Bottles of 90 NDC 60505-4665-9 Storage and Handling Store tasimelteon capsules at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Protect from exposure to light and moisture.

📋 Description 140 words

11 DESCRIPTION Tasimelteon is a melatonin receptor agonist, chemically designated as (1 R-trans )- N -[[2-(2,3-Dihydrobenzofuran-4-yl)cycloprop-1-yl]methyl]propanamide, containing two chiral centers. The molecular formula is C 15 H 19 NO 2 , and the molecular weight is 245.32 g/mol. The structural formula is: Tasimelteon is a white to off-white powder.

It is very slightly soluble in cyclohexane, slightly soluble in water and freely soluble or very soluble in methanol, 95% ethanol, acetonitrile, isopropanol, propylene glycol and ethyl acetate. Tasimelteon capsules are intended for oral administration. Each capsule contains 20 mg of tasimelteon and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, 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. The imprinting ink consists of povidone, propylene glycol, shellac, sodium hydroxide and titanium dioxide.

💬 Information for Patients 173 words

17 PATIENT COUNSELING INFORMATION Advise patients to limit their activities to preparing for going to bed after taking tasimelteon capsules because tasimelteon can potentially impair the performance of activities requiring complete mental alertness [see Warnings and Precautions ( 5.1 )] . Administration Information for tasimelteon capsules [see Dosage and Administration ( 2.1 , 2.2 , 2.4 )] . Advise patients to take tasimelteon capsules without food.

Advise patients to take tasimelteon capsules before bedtime at the same time every night. Advise patients to skip the dose that night if they cannot take tasimelteon capsules at approximately the same time on a given night. Advise patients to swallow tasimelteon capsules whole.

Non-24 (tasimelteon capsules) Advise patients that because of individual differences in circadian rhythms, daily use for several weeks or months may be necessary before benefit from tasimelteon capsules is observed [see Dosage and Administration ( 2.2 )] . APOTEX INC. TASIMELTEON CAPSULES 20 mg Manufactured By Apotex Inc.

Toronto, Ontario Canada M9L 1T9 Manufactured For Apotex Corp. Weston, Florida USA 33326 Rev. 5

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
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