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SAPHRIS Asenapine Maleate 5 mg Tablet, 10-count — NDC 00456-2405-10 package photo

SAPHRIS Asenapine Maleate 5 mg Tablet, 10-count

by Allergan, Inc. · 1 CASE in 1 CARTON (0456-2405-10) / 1 BLISTER PACK in 1 CASE / 10 TABLET in 1 BLISTER PACK
NDC 00456-2405-10
🏷️ FDA NDC (as labeled) 0456-2405-10 billing pads the labeler segment with a zero
This package
Contains10-count Pack sizes2 compare ↓
Also priced by: Part D plans $22.67/unit — full pricing hub ↓
Also comes in: 60 tablets 00456-2405-60
Rx only Brand 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 →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 0456-2405-10
Product NDC 0456-2405
11-digit billing NDC 00456240510
RxCUI 859975, 859979, 859981, 859983, 1606337, 1606490
UNII CU9463U2E2
Application # NDA022117
SPL Set ID 5429f134-839f-4ffc-9944-55f51238def8
Established class (EPC) Atypical Antipsychotic
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2013-09-30
Route SUBLINGUAL
Dosage form TABLET
Substance ASENAPINE MALEATE
GPI-14 59155015100720
GPI class Saphris
GCN Seq No 065537
GCN 21636
HICL code 036576
Ingredient (HICL) Asenapine Maleate
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H7
Therapeutic class — intermediate (HIC2) Psychoactive Drugs (Continued 1)
HIC3 code H7T
Therapeutic class — specific (HIC3) Antipsychotic,Atypical,Dopamine,Serotonin Antagnst
AHFS code 28:16.08.04
AHFS class Atypical Antipsychotics
FDB label name SAPHRIS 5 MG TAB SUBLINGUAL
FDB brand name Saphris
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 0456-2405-10 — a 4-4-2 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 labeler segment → 00456-2405-10. 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 Atypical Antipsychotic class.

Pharmacologic class Atypical Antipsychotic
Drug family (ATC) Diazepines, oxazepines, thiazepines and oxepines
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

LabelerAllergan, Inc.
Application holderABBVIE INC
FDA applicationNDA022117 (NDA)
Labeler code00456
First marketedSep 2013
Product typeHuman Prescription Drug
Portfolio188 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 SAPHRIS 5 MG TAB SUBLINGUAL Ingredient Asenapine Maleate
📖 What it is MedlinePlus · NLM

Asenapine is used to treat the symptoms of schizophrenia (a mental illness that affects how a person thinks, feels and behaves) and bipolar I disorder (a disease that causes depression, mania, and other abnormal moods). Asenapine is in a class of medications called atypical antipsychotics. It works by changing the activity of certain natural substances in the brain.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • This is really important — swallowing the tablet dramatically reduces how much of the medication actually gets into your system. When it dissolves under your tongue, it absorbs dir...
  • Why do I have to let the tablet dissolve under my tongue instead of just swallowing it?
  • Yes, sleepiness and dizziness are among the most commonly reported side effects, especially early on. The dizziness can be worse when you stand up quickly, because asenapine can ca...
  • I feel really sleepy and dizzy since starting this — is that normal?
📖 Read our full Asenapine guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
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 white
ShapeRound
Imprint10
Size12 mm
ScoringNot scored
FlavorCherry
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 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 3OWL53L36A
    A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
  • UNII 96K6UQ3ZD4
    Sucralose is a synthetic sweetener made from sugar. It's added to medicines to improve taste without adding calories, helping make bitter or unpleasant-tasting drugs easier to take.

3 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 DailyMed — ingredient 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 eachPer 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 $22.67 $226.74 / 10 tablets
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
Asenapine 5 mg 62332-0198-31 Alembic 1000 tablets $2.148 AB Availability likely —
Saphris 5 mgthis 00456-2405-10 Allergan, 10 tablets — AB FDA listed —
Asenapine 5 mg 42794-0016-08 Sigmapharm 30 tablets — AB FDA listed —
Asenapine 5 mg 46708-0198-31 Alembic 1000 tablets — AB FDA listed —
Asenapine 5 mg 51991-0358-11 Breckenridge 100 tablets — AB FDA listed —
Asenapine 5 mg 51991-0359-11 Breckenridge 100 tablets — AB FDA listed —
Asenapine 5 mg 69539-0057-34 MSN 60 tablets — AB FDA listed —
Asenapine 5 mg 69539-0058-34 MSN 60 tablets — AB FDA listed —
About this product: this is the brand-name version. FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available.
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

🏛️
2009
First FDA approval
Aug 2009
📍
2026
Currently FDA-listed
17 years listed
🛡️
2026
Latest patent/protection listed
not a guaranteed launch date
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Oct 2026. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Aug 13, 2009 AB TE-rated RLD RS ⏳ ~0.1 yr to latest listed protection

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.

Patents & exclusivity — FDA Orange Book
US 7741358 — drug substance (U-1960)
US 7741358 — drug substance (U-1064)
US 7741358 — drug substance (U-1963)
US 7741358 — drug substance (U-1064)
US 7741358 — drug substance (U-1966)
US 7741358 — drug substance (U-1961)
US 7741358 — drug substance (U-1961)
US 7741358 — drug substance (U-1960)
US 7741358 — drug substance (U-1893)
US 7741358 — drug substance (U-1962)
US 7741358 — drug substance (U-1963)
US 7741358 — drug substance (U-1962)
US 8022228 — drug substance
US 8022228 — drug substance
US 8022228 — drug substance
US 7741358*PED — drug product
US 7741358*PED — drug product
US 8022228*PED — drug product
US 8022228*PED — drug product
US 7741358*PED — drug product
US 8022228*PED — drug product
2009 2011 2013 2015 2017 2019 2021 2023 2025
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 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.

Listed patents (21)
PatentTypeUse codeExpires
US 7741358 ↗ Drug substance U-1960 Apr 6, 2026
US 7741358 ↗ Drug substance U-1064 Apr 6, 2026
US 7741358 ↗ Drug substance U-1963 Apr 6, 2026
US 7741358 ↗ Drug substance U-1064 Apr 6, 2026
US 7741358 ↗ Drug substance U-1966 Apr 6, 2026
US 7741358 ↗ Drug substance U-1961 Apr 6, 2026
US 7741358 ↗ Drug substance U-1961 Apr 6, 2026
US 7741358 ↗ Drug substance U-1960 Apr 6, 2026
US 7741358 ↗ Drug substance U-1893 Apr 6, 2026
US 7741358 ↗ Drug substance U-1962 Apr 6, 2026
US 7741358 ↗ Drug substance U-1963 Apr 6, 2026
US 7741358 ↗ Drug substance U-1962 Apr 6, 2026
US 8022228 ↗ Drug substance — Apr 6, 2026
US 8022228 ↗ Drug substance — Apr 6, 2026
US 8022228 ↗ Drug substance — Apr 6, 2026
US 7741358*PED ↗ Drug product — Oct 6, 2026
US 7741358*PED ↗ Drug product — Oct 6, 2026
US 8022228*PED ↗ Drug product — Oct 6, 2026
US 8022228*PED ↗ Drug product — Oct 6, 2026
US 7741358*PED ↗ Drug product — Oct 6, 2026
US 8022228*PED ↗ Drug product — Oct 6, 2026
Common questions
Is there a generic version of SAPHRIS 5 MG TAB SUBLINGUAL?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for SAPHRIS 5 MG TAB SUBLINGUAL. See the alternatives section for substitutable, lower-cost products.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
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 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.
10 tablets00456-2405-60 4,420 Rx · $4,722,949
10 tablets this page00456-2405-10 No Medicaid data
Drug total (last 4 qtrs): 4,420 Rx · 233,837 units · $4,722,949 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 Saphris — the program that covers self-administered drugs. 1 manufacturer.
⚠️ 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 Saphris. 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
$1.42M
Claims incl. refills
1.2K
Beneficiaries
519
Spend / beneficiary
$2,740.35
Spend / claim
$1,154.42
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 SAPHRIS (this brand).

Top reported reactions

Sedation667
Suicide Attempt651
Inappropriate Schedule Of Drug Administration557
Weight Increased535
Dyskinesia519
Dystonia496
Blood Glucose Increased477

Age at onset

Neonate1
Child4
Adolescent4
Adult336
Elderly16

Reporter sex

7,792 reports

Serious outcomes

Death278
Disabling193
Reports over time (by year) — tap or hover for the count & year
2020 2022 2024 2026 265 0
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
00456-2405-10 You're viewing this 1 CASE in 1 CARTON (0456-2405-10) / 1 BLISTER PACK in 1 CASE / 10 TABLET in 1 BLISTER PACK — — 2013-09-30 Active
00456-2405-60 6 CASE in 1 CARTON (0456-2405-60) / 1 BLISTER PACK in 1 CASE (0456-2405-06) / 10 TABLET in 1 BLISTER PACK $21.18 / ea $1,270.85 2013-09-30 Active

This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 00456-2405-10?
NDC 00456-2405-10 is a 10-count package — 1 case in 1 carton / 1 blister pack in 1 case / 10 tablet in 1 blister pack.
What is the difference between NDC 00456-2405-10 and NDC 00456-2405-60?
Both are SAPHRIS Asenapine Maleate 5 mg Tablet — the drug itself is identical. NDC 00456-2405-10 is the 10-count package, while NDC 00456-2405-60 is the 60 tablets package.
What NDC number is used to bill for this package of SAPHRIS Asenapine Maleate 5 mg Tablet?
Bill NDC 00456-2405-10 — the 11-digit billing format is 00456240510. 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.

🧭 About this NDC listing & data coverage

Finished prescription product
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) ✓ 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.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 0456-2405-10, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00456-2405-10, written without dashes as 00456240510. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 00456-2405-10, the first segment (00456) is the labeler code FDA assigned to Allergan, Inc.; the middle segment (2405) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (10) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Allergan, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 60 tablets (00456-2405-60). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Allergan, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 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.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning 98 words ▾

WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. SAPHRIS ® (asenapine) is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions ( 5.1, 5.2 )] . WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS See full prescribing information for complete boxed warning.

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis. ( 5.1 , 5.2 )

🎯 Indications and Usage 112 words ▾

1 INDICATIONS AN D USAGE SAPHRIS is indicated for: Schizophrenia in adults [see Clinical Studies ( 14.1 )] Bipolar I disorder [see Clinical Studies ( 14.2 )] • Acute monotherapy of manic or mixed episodes, in adults and pediatric patients 10 to 17 years of age • Adjunctive treatment to lithium or valproate in adults • Maintenance monotherapy treatment in adults SAPHRIS is an atypical antipsychotic indicated for ( 1 ): Schizophrenia in adults Bipolar I disorder ○ Acute monotherapy treatment of manic or mixed episodes, in adults and pediatric patients 10 to 17 years of age ○ Adjunctive treatment to lithium or valproate in adults ○ Maintenance monotherapy treatment in adults

⏱️ Dosage and Administration ~3 min read ▾

2 D OSAGE AND ADMINISTRATION Starting Dose Recommended Dose Maximum Dose Schizophrenia – acute treatment in adults ( 2.2 ) 5 mg sublingually twice daily 5 mg sublingually twice daily 10 mg sublingually twice daily Schizophrenia – maintenance treatment in adults ( 2.2 ) 5 mg sublingually twice daily 5-10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania – adults: acute and maintenance monotherapy ( 2.3 ) 5-10 mg sublingually twice daily 5-10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania –pediatric patients (10 to 17 years): monotherapy ( 2.3 ) 2.5 mg sublingually twice daily 2.5-10 mg sublingually twice daily 10 mg sublingually twice daily Bipolar mania – adults: as an adjunct to lithium or valproate ( 2.3 ) 5 mg sublingually twice daily 5-10 mg sublingually twice daily 10 mg sublingually twice daily Do not swallow tablet.

SAPHRIS sublingual tablets should be placed under the tongue and left to dissolve completely. The tablet will dissolve in saliva within seconds. Eating and drinking should be avoided for 10 minutes after administration.

( 2.1 , 17 )

2.1Administration Instructions SAPHRIS is a sublingual tablet. To ensure optimal absorption, patients should be instructed to place the tablet under the tongue and allow it to dissolve completely. The tablet will dissolve in saliva within seconds.

SAPHRIS sublingual tablets should not be split, crushed, chewed, or swallowed [see Clinical Pharmacology ( 12.3 ) ] . Patients should be instructed to not eat or drink for 10 minutes after administration [see Clinical Pharmacology ( 12.3 ) ] .

2.2Schizophrenia The recommended dose of SAPHRIS is 5 mg given twice daily. In short-term controlled trials, there was no suggestion of added benefit with a 10 mg twice daily dose, but there was a clear increase in certain adverse reactions. If tolerated, daily dosage can be increased to 10 mg twice daily after one week. The safety of doses above 10 mg twice daily has not been evaluated in clinical studies [see Clinical Studies ( 14.1 )] .

2.3Bipolar I Disorder Acute Treatment of Manic or Mixed Episodes : Monotherapy in Adults : The recommended starting and treatment dose of SAPHRIS is 5 mg to 10 mg twice daily. The safety of doses above 10 mg twice daily has not been evaluated in clinical trials [see Clinical Studies ( 14.2 )] . Monotherapy in Pediatric P atients: The recommended dose of SAPHRIS is 2.5 mg to 10 mg twice daily in pediatric patients 10 to 17 years of age, and dose may be adjusted for individual response and tolerability.

The starting dose of SAPHRIS is 2.5 mg twice daily. After 3 days, the dose can be increased to 5 mg twice daily, and from 5 mg to 10 mg twice daily after 3 additional days. Pediatric patients aged 10 to 17 years appear to be more sensitive to dystonia with initial dosing with SAPHRIS when the recommended escalation schedule is not followed [see Use in Specific Populations ( 8.4 )] .

The safety of doses greater than 10 mg twice daily has not been evaluated in clinical trials [see Use in Specific Populations ( 8.4 ) and Clinical Pharmacology ( 12.3 )] . Adjunctive Therapy in Adults : The recommended starting dose of SAPHRIS is 5 mg twice daily when administered as adjunctive therapy with either lithium or valproate. Depending on the clinical response and tolerability in the individual patient, the dose can be increased to 10 mg twice daily.

The safety of doses above 10 mg twice daily as adjunctive therapy with lithium or valproate has not been evaluated in clinical trials. For patients on SAPHRIS, whether used as monotherapy or as adjunctive therapy with lithium or valproate, it is generally recommended that responding patients continue treatment beyond the acute episode. Maintenance Trea tment of Bipolar I Disorder: Monotherapy in Adults: Continue on the SAPHRIS dose that the patient received during stabilization (5 mg to 10 mg twice daily).

Depending on the clinical response and tolerability in the individual pati…

💊 Dosage Forms and Strengths 85 words ▾

3 DOSAGE FORM S AND STRENGTHS SAPHRIS 2.5 mg tablets, black cherry flavor, are round, white to off-white sublingual tablets, with a hexagon on one side. SAPHRIS 5 mg tablets, black cherry flavor, are round, white to off-white sublingual tablets, with “5” on one side within a circle. SAPHRIS 10 mg tablets, black cherry flavor, are round, white to off-white sublingual tablets, with “10” on one side within a circle.

Sublingual tablets, black cherry flavor: 2.5 mg, 5 mg and 10 mg ( 3 )

⛔ Contraindications 87 words ▾

4 CONTRAINDICATIONS SAPHRIS is contraindicated in patients with: Severe hepatic impairment (Child-Pugh C) [see Specific Populations ( 8.7 ), Clinical Pharmacology ( 12.3 )] . A history of hypersensitivity reactions to asenapine. Reactions have included anaphylaxis, angioedema, hypotension, tachycardia, swollen tongue, dyspnea, wheezing and rash [see Warnings and Precautions ( 5.6 ), Adverse Reactions ( 6 )] .

Severe hepatic impairment (Child-Pugh C). ( 8.7 , 12.3 ) Known hypersensitivity to SAPHRIS (asenapine), or to any components in the formulation. ( 4 , 5.6 , 17 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis : Increased incidence of cerebrovascular adverse reactions (e.g., stroke, transient ischemic attack). ( 5.2 ) Neuroleptic Malignant Syndrome: Manage with immediate discontinuation and close monitoring. ( 5.3 ) Tardive Dyskinesia : Discontinue if clinically appropriate.

( 5.4 ) Metabolic Changes : Monitor for hyperglycemia/diabetes mellitus, dyslipidemia, and weight gain. ( 5.5 ) Orthostatic Hypotension: Monitor heart rate and blood pressure and warn patients with known cardiovascular or cerebrovascular disease, and risk of dehydration or syncope. ( 5.7 ) Leukopenia, Neutropenia, and Agranulocytosis : Perform complete blood counts (CBC) in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia.

Consider discontinuing SAPHRIS if a clinically significant decline in WBC occurs in absence of other causative factors. ( 5.9 ) QT Prolongation: Increases in QT interval; avoid use with drugs that also increase the QT interval and in patients with risk factors for prolonged QT interval. ( 5.10 ) Seizures: Use cautiously in patients with a history of seizures or with conditions that lower the seizure threshold.

( 5.12 ) Potential for Cognitive and Motor Impairment: Use caution when operating machinery. ( 5.13 )

5.1Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group.

Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis [ see Boxed Warning and Warnings and Precautions ( 5.2 ) ] .

5.2Cerebrovascular Adverse Events, Including Stroke, In Elderly Patients with Dementia-Related Psychosis In placebo-controlled trials in elderly subjects with dementia, patients randomized to risperidone, aripiprazole, and olanzapine had a higher incidence of stroke and transient ischemic attack, including fatal stroke. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning , Warnings and Precautions ( 5.1 )] .

5.3Neuroleptic Malignant Syndrome A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, delirium, and autonomic instability. Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.

If NMS is suspected, immediately discontinue SAPHRIS and provide intensive symptomatic treatment and monitoring.

5.4Tardive Dyskinesia Tardive dyskinesia, a syndrome consisting of potentially irreversible, involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs, including SAPHRIS. The risk appears to be highest among the elderly, especially elderly women, but it is not possible to predict which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

The risk of tardive dyskinesia and the likelihood that it will become irreversible increase with the duration of treatment and the cumulative dose. The syndrome can develop after a relatively brief treatm…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Use in Elderly Patients with Dementia-Related Psychosis [see Boxed Warning and Warnings and Precautions ( 5.1 and 5.2 )] Neuroleptic Malignant Syndrome [see Warnings and Precautions ( 5.3 )] Tardive Dyskinesia [see Warnings and Precautions ( 5.4 )] Metabolic Changes [see Warnings and Precautions ( 5.5 )] Hypersensitivity Reactions [see Contraindications, Warnings and Precautions ( 5.6 )] Orthostatic Hypotension, Syncope, and other Hemodynamic Effects [see Warnings and Precautions ( 5.7 )] Falls [see Warnings and Precautions ( 5.8 )] Leukopenia, Neutropenia, and Agranulocytosis [see Warnings and Precautions ( 5.9 )] QT Interval Prolongation [see Warnings and Precautions ( 5.10 )] Hyperprolactinemia [see Warnings and Precautions ( 5.11 )] Seizures [see Warnings and Precautions ( 5.12 )] Potential for Cognitive and Motor Impairment [see Warnings and Precautions ( 5.13 )] Body Temperature Regulation [see Warnings and Precautions ( 5.14 )] Dysphagia [see Warnings and Precautions ( 5.15 )] The most common adverse reactions (≥5% and at least twice the rate of placebo) reported with acute treatment in adults with schizophrenia were akathisia, oral hypoesthesia, and somnolence.

The safety profile of SAPHRIS in the maintenance treatment of schizophrenia in adults was similar to that seen with acute treatment. The most common adverse reactions (≥5% and at least twice the rate of placebo) reported with acute monotherapy treatment of manic or mixed episodes associated with bipolar I disorder in adults were somnolence, oral hypoesthesia dizziness, extrapyramidal symptoms (excluding akathisia) and akathisia; and during the adjunctive therapy trial in bipolar I disorder in adults were somnolence and oral hypoesthesia.

The rates were lower at the 5mg twice daily dose than the 10mg twice daily dose for all of these most common adverse reactions. The safety profile of SAPHRIS in the maintenance treatment of manic or mixed episodes associated with bipolar I disorder in adults was similar to that seen with acute treatment. The adult information below is derived from a clinical trial database for SAPHRIS consisting of over 5355 patients and/or healthy subjects exposed to one or more sublingual doses of SAPHRIS.

A total of 1427 SAPHRIS-treated patients were treated for at least 24 weeks and 785 SAPHRIS-treated patients had at least 52 weeks of exposure at therapeutic doses. In a 3-week monotherapy trial, the most common adverse reactions (≥5% and at least twice the rate of placebo) reported in pediatric patients with bipolar I disorder treated with SAPHRIS were somnolence, dizziness, dysgeusia, oral hypoesthesia, nausea, increased appetite, fatigue, and increased weight. No new major safety findings were reported from a 50-week, open-label, uncontrolled safety trial.

A total of 651 pediatric patients were treated with SAPHRIS. Of these patients, 352 pediatric patients were treated with SAPHRIS for at least 180 days and 58 pediatric patients treated with SAPHRIS had at least 1 year of exposure. The safety of SAPHRIS was evaluated in 403 pediatric patients with bipolar I disorder who participated in a 3-week, placebo-controlled, double-blind trial, of whom 302 patients received SAPHRIS at fixed doses ranging from 2.5 mg to 10 mg twice daily.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced a treatment-emergent adverse event of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. The most commonly observed adverse reactions (incidence ≥5% and at least twice that for placebo) were ( 6.1 ): Schizophrenia Adults : akathisia, oral hypoesthesia, somnolence.

Bipolar I Disorder Adults (Monotherapy): somnolence, oral hypoesthesia, dizziness, extrapyramidal symptoms (excluding akathisia) a…

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Antihypertensive Drugs: SAPHRIS may cause hypotension. ( 5.7 , 7.1 , 12.3 ) Paroxetine (CYP2D6 substrate and inhibitor): Reduce paroxetine by half when used in combination with SAPHRIS. ( 7.1 , 12.3 )

7.1Drugs Having Clinically Important Drug Interactions with SAPHRIS Table 12: Clinically Important Drug Interactions with SAPHRIS Concomitant Drug Name or Drug Class Clinical Rationale Clinical Recommendation Antihypertensive Drugs Because of its α 1 -adrenergic antagonism with potential for inducing hypotension, SAPHRIS may enhance the effects of certain antihypertensive agents [see Warnings and Precautions ( 5.7 )] . Monitor blood pressure and adjust dosage of antihypertensive drug accordingly. Strong CYP1A2 Inhibitors (e.g., Fluvoxamine) SAPHRIS is metabolized by CYP1A2.

Marginal increase of asenapine exposure was observed when SAPHRIS is used with fluvoxamine at 25 mg administered twice daily [ see Clinical Pharmacology ( 12.3 )] . However, the tested fluvoxamine dose was suboptimal. Full therapeutic dose of fluvoxamine is expected to cause a greater increase in asenapine exposure.

Dosage reduction for SAPHRIS based on clinical response may be necessary. CYP2D6 substrates and inhibitors (e.g., paroxetine) SAPHRIS may enhance the inhibitory effects of paroxetine on its own metabolism. Concomitant use of paroxetine with SAPHRIS increased the paroxetine exposure by 2-fold as compared to use paroxetine alone [see Clinical Pharmacology ( 12.3 )].

Reduce paroxetine dose by half when paroxetine is used in combination with SAPHRIS.

7.2Drugs Having No Clinically Important Interactions with SAPHRIS No dosage adjustment of SAPHRIS is necessary when administered concomitantly with paroxetine (see Table 12 in Drug Interactions ( 7.1 ) for paroxetine dosage adjustment), imipramine, cimetidine, valproate, lithium, or a CYP3A4 inducer (e.g., carbamazepine, phenytoin, rifampin). In addition, valproic acid and lithium pre-dose serum concentrations collected from an adjunctive therapy study were comparable between asenapine-treated patients and placebo-treated patients indicating a lack of effect of asenapine on valproic and lithium plasma levels.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: May cause extrapyramidal and/or withdrawal symptoms in neonates with third trimester exposure. ( 8.1 ) Pediatric Use: Safety and efficacy in the treatment of bipolar I disorder in patients less than 10 years of age, and patients with schizophrenia ages less than 12 years have not been evaluated. ( 8.4 )

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SAPHRIS during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry / . Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms.

Studies have not been conducted with SAPHRIS in pregnant women. There are no available human data informing the drug-associated risk. The background risk of major birth defects and miscarriage for the indicated populations are unknown.

However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. No teratogenicity was observed in animal reproduction studies with intravenous administration of asenapine to rats and rabbits during organogenesis at doses 0.7 and 0.4 times, respectively, the maximum recommended human dose (MRHD) of 10 mg sublingually twice daily. In a pre-and post-natal study in rats, intravenous administration of asenapine at doses up to 0.7 times the MRHD produced increases in post-implantation loss and early pup deaths, and decreases in subsequent pup survival and weight gain [see Data].

Advise pregnant women of the potential risk to a fetus. Clinical Considerations Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy. These symptoms have varied in severity.

Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Data Animal Data In animal studies, asenapine increased post-implantation loss and decreased pup weight and survival at doses similar to or less than recommended clinical doses.

In these studies there was no increase in the incidence of structural abnormalities caused by asenapine. Asenapine was not teratogenic in reproduction studies in rats and rabbits at intravenous doses up to 1.5 mg/kg in rats and 0.44 mg/kg in rabbits administered during organogenesis. These doses are 0.7 and 0.4 times, respectively, the maximum recommended human dose (MRHD) of 10 mg twice daily given sublingually on a mg/m 2 basis.

Plasma levels of asenapine were measured in the rabbit study, and the area under the curve (AUC) at the highest dose tested was 2 times that in humans receiving the MRHD. In a study in which rats were treated from day 6 of gestation through day 21 postpartum with intravenous doses of asenapine of 0.3, 0.9, and 1.5 mg/kg/day (0.15, 0.4, and 0.7 times the MRHD of 10 mg twice daily given sublingually on a mg/m 2 basis), increases in post-implantation loss and early pup deaths were seen at all doses, and decreases in subsequent pup survival and weight gain were seen at the two higher doses.

A cross-fostering study indicated that the decreases in pup survival were largely due to prenatal drug effects. Increases in post-implantation loss and decreases in pup weight and survival were also seen when pregnant rats were dosed orally with asenapine. 8.

2 Lactation Risk Summary Lactation studies have not been conducted to assess the presence of asenapine in human milk, the effects of asena…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to SAPHRIS during pregnancy. For more information contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry / . Risk Summary Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms.

Studies have not been conducted with SAPHRIS in pregnant women. There are no available human data informing the drug-associated risk. The background risk of major birth defects and miscarriage for the indicated populations are unknown.

However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. No teratogenicity was observed in animal reproduction studies with intravenous administration of asenapine to rats and rabbits during organogenesis at doses 0.7 and 0.4 times, respectively, the maximum recommended human dose (MRHD) of 10 mg sublingually twice daily. In a pre-and post-natal study in rats, intravenous administration of asenapine at doses up to 0.7 times the MRHD produced increases in post-implantation loss and early pup deaths, and decreases in subsequent pup survival and weight gain [see Data].

Advise pregnant women of the potential risk to a fetus. Clinical Considerations Fetal/Neonatal Adverse Reactions Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder have been reported in neonates who were exposed to antipsychotic drugs during the third trimester of pregnancy. These symptoms have varied in severity.

Some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization. Monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately. Data Animal Data In animal studies, asenapine increased post-implantation loss and decreased pup weight and survival at doses similar to or less than recommended clinical doses.

In these studies there was no increase in the incidence of structural abnormalities caused by asenapine. Asenapine was not teratogenic in reproduction studies in rats and rabbits at intravenous doses up to 1.5 mg/kg in rats and 0.44 mg/kg in rabbits administered during organogenesis. These doses are 0.7 and 0.4 times, respectively, the maximum recommended human dose (MRHD) of 10 mg twice daily given sublingually on a mg/m 2 basis.

Plasma levels of asenapine were measured in the rabbit study, and the area under the curve (AUC) at the highest dose tested was 2 times that in humans receiving the MRHD. In a study in which rats were treated from day 6 of gestation through day 21 postpartum with intravenous doses of asenapine of 0.3, 0.9, and 1.5 mg/kg/day (0.15, 0.4, and 0.7 times the MRHD of 10 mg twice daily given sublingually on a mg/m 2 basis), increases in post-implantation loss and early pup deaths were seen at all doses, and decreases in subsequent pup survival and weight gain were seen at the two higher doses.

A cross-fostering study indicated that the decreases in pup survival were largely due to prenatal drug effects. Increases in post-implantation loss and decreases in pup weight and survival were also seen when pregnant rats were dosed orally with asenapine.

🧒 Pediatric Use ~3 min read ▾

8.4Pediatric Use Safety and efficacy of SAPHRIS in pediatric patients below the age of 10 years of age have not been evaluated. Bipolar I Disorder The safety and efficacy of SAPHRIS as monotherapy in the treatment of bipolar I disorder were established in a 3-week, placebo-controlled, double-blind trial of 403 pediatric patients 10 to 17 years of age, of whom 302 patients received SAPHRIS at fixed doses ranging from 2.5 mg to 10 mg twice daily [see Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.2 )] .

In a Phase 1 study, pediatric patients aged 10 to 17 years appeared to be more sensitive to dystonia with initial dosing with asenapine when the recommended dose escalation schedule was not followed. Similar safety findings were reported from a 50-week, open-label, uncontrolled safety trial in pediatric patients with bipolar I disorder treated with SAPHRIS monotherapy. The safety and efficacy of SAPHRIS as adjunctive therapy in the treatment of bipolar I disorder have not been established in the pediatric population.

In general, the pharmacokinetics of asenapine in pediatric patients (10 to 17 years) and adults are similar [see Clinical Pharmacology ( 12.3 )] . Schizophrenia Efficacy of SAPHRIS was not demonstrated in an 8-week, placebo-controlled, double-blind trial, in 306 adolescent patients aged 12 to 17 years with schizophrenia at doses of 2.5 and 5 mg twice daily. The most common adverse reactions (proportion of patients equal or greater than 5% and at least twice placebo) reported were somnolence, akathisia, dizziness, and oral hypoesthesia or paresthesia.

The proportion of patients with an equal or greater than 7% increase in body weight at endpoint compared to baseline for placebo, SAPHRIS 2.5 mg twice daily, and SAPHRIS 5 mg twice daily was 3%, 10%, and 10%, respectively. The clinically relevant adverse reactions identified in the pediatric schizophrenia trial were generally similar to those observed in the pediatric bipolar I and adult bipolar I and schizophrenia trials. No new major safety findings were reported from a 26-week, open-label, uncontrolled safety trial in pediatric patients with schizophrenia treated with SAPHRIS monotherapy.

Juvenile Animal Data Subcutaneous administration of asenapine to juvenile rats for 56 days from day 14 of age to day 69 of age at 0.4, 1.2, and 3.2 mg/kg/day (0.2, 0.6 and 1.5 times the maximum recommended human dose of 10 mg twice daily given sublingually on a mg/m 2 basis) resulted in significant reduction in body weight gain in animals of both sexes at all dose levels from the start of dosing until weaning. Body weight gain remained reduced in males to the end of treatment, however, recovery was observed once treatment ended.

Neurobehavioral assessment indicated increased motor activity in animals at all dose levels following the completion of treatment, with the evidence of recovery in males. There was no recovery after the end of treatment in female activity pattern as late as day 30 following the completion of treatment (last retesting). Therefore, a No Observed Adverse Effect Level (NOAEL) for the juvenile animal toxicity of asenapine could not be determined.

There were no treatment-related effects on the startle response, learning/memory, organ weights, microscopic evaluations of the brain and, reproductive performance (except for minimally reduced conception rate and fertility index in males and females administered 1.2 and 3.2 mg/kg/day).

🧓 Geriatric Use 145 words ▾

8.5Geriatric Use Clinical studies of SAPHRIS in the treatment of schizophrenia and bipolar mania did not include sufficient numbers of patients aged 65 and over to determine whether or not they respond differently than younger patients. Of the approximately 2250 patients in pre-marketing clinical studies of SAPHRIS, 1.1% (25) were 65 years of age or over. Multiple factors that might increase the pharmacodynamic response to SAPHRIS, causing poorer tolerance or orthostasis, could be present in elderly patients, and these patients should be monitored carefully.

Based on a pharmacokinetic study in elderly patients, dosage adjustments are not recommended based on age alone [see Clinical Pharmacology ( 12.3 )] . Elderly patients with dementia-related psychosis treated with SAPHRIS are at an increased risk of death compared to placebo. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis [ see Boxed Warning ] .

🆘 Overdosage 178 words ▾

10 OV ERDOSAGE Human Experience: In adult pre-marketing clinical studies involving more than 3350 patients and/or healthy subjects, accidental or intentional acute overdosage of SAPHRIS was identified in 3 patients. Among these few reported cases of overdose, the highest estimated ingestion of SAPHRIS was 400 mg. Reported adverse reactions at the highest dosage included agitation and confusion.

Management of Overdosage: There is no specific antidote to SAPHRIS. The possibility of multiple drug involvement should be considered. An electrocardiogram should be obtained and management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms.

Consult with a Certified Poison Control Center for up-to-date guidance and advice on the management of overdosage (1-800-222-1222.) Hypotension and circulatory collapse should be treated with appropriate measures, such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should not be used, since beta stimulation may worsen hypotension in the setting of SAPHRIS-induced alpha blockade). In case of severe extrapyramidal symptoms, anticholinergic medication should be administered. Close medical supervision and monitoring should continue until the patient recovers.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY Figure 1 Figure 2 Figure 3

12.1Mechanism of Action The mechanism of action of asenapine, in schizophrenia and bipolar I disorder, is unknown. It has been suggested that the efficacy of asenapine in schizophrenia could be mediated through a combination of antagonist activity at D 2 and 5-HT 2A receptors.

12.2Pharmacodynamics Asenapine exhibits high affinity for serotonin 5-HT 1A , 5-HT 1B , 5-HT 2A , 5-HT 2B , 5-HT 2C , 5-HT 5A , 5-HT 6, and 5-HT 7 receptors (Ki values of 2.5, 2.7, 0.07, 0.18, 0.03, 1.6, 0.25, and 0.11 nM, respectively), dopamine D 2A , D 2B , D 3 , D 4 , and D 1 receptors (Ki values of 1.3, 1.4, 0.42, 1.1, and 1.4 nM, respectively), α 1A , α 2A , α 2B , and α 2C -adrenergic receptors (Ki values of 1.2, 1.2, 0.33 and 1.2 nM, respectively), and histamine H 1 receptors (Ki value 1.0 nM), and moderate affinity for H 2 receptors (Ki value of 6.2 nM).

In in vitro assays asenapine acts as an antagonist at these receptors. Asenapine has no appreciable affinity for muscarinic cholinergic receptors (e.g., Ki value of 8128 nM for M 1 ).

12.3Pharmacokinetics Following a single 5 mg dose of SAPHRIS, the mean C max was approximately 4 ng/mL and was observed at a mean t max of 1 hour. Elimination of asenapine is primarily through direct glucuronidation by UGT1A4 and oxidative metabolism by cytochrome P450 isoenzymes (predominantly CYP1A2). Following an initial more rapid distribution phase, the mean terminal half-life is approximately 24 hrs.

With multiple-dose twice-daily dosing, steady-state is attained within 3 days. Overall, steady-state asenapine pharmacokinetics are similar to single-dose pharmacokinetics. Absorption: Following sublingual administration, asenapine is rapidly absorbed with peak plasma concentrations occurring within 0.5 to 1.5 hours.

The absolute bioavailability of sublingual asenapine at 5 mg is 35%. Increasing the dose from 5 mg to 10 mg twice daily (a two-fold increase) results in less than linear (1.7 times) increases in both the extent of exposure and maximum concentration. The absolute bioavailability of asenapine when swallowed is low (<2% with an oral tablet formulation).

The intake of water several (2 or 5) minutes after asenapine administration resulted in decreased asenapine exposure. Therefore, eating and drinking should be avoided for 10 minutes after administration [see Dosage and Administration ( 2.1 )] . Distribution: Asenapine is rapidly distributed and has a large volume of distribution (approximately 20 - 25 L/kg), indicating extensive extravascular distribution.

Asenapine is highly bound (95%) to plasma proteins, including albumin and α 1 -acid glycoprotein. Metabolism and Elimination: Direct glucuronidation by UGT1A4 and oxidative metabolism by cytochrome P450 isoenzymes (predominantly CYP1A2) are the primary metabolic pathways for asenapine. Asenapine is a high clearance drug with a clearance after intravenous administration of 52 L/h.

In this circumstance, hepatic clearance is influenced primarily by changes in liver blood flow rather than by changes in the intrinsic clearance, i.e., the metabolizing enzymatic activity. Following an initial more rapid distribution phase, the terminal half-life of asenapine is approximately 24 hours. Steady-state concentrations of asenapine are reached within 3 days of twice daily dosing.

After administration of a single dose of [ 14 C]-labeled asenapine, about 90% of the dose was recovered; approximately 50% was recovered in urine, and 40% recovered in feces. About 50% of the circulating species in plasma have been identified. The predominant species was asenapine N + -glucuronide; others included N-desmethylasenapine, N-desmethylasenapine N-carbamoyl glucuronide, and unchanged asenapine in smaller amounts.

SAPHRIS activity is primarily due to the parent drug. In vitro studies indicate that asenapine is a substrate for UGT1A4, CYP1A2 and to a lesser extent CYP3A4 and CYP2D6. Asenapine is a weak inhibitor of CYP2D6.

Asen…

🧬 Mechanism of Action 45 words ▾

12.1Mechanism of Action The mechanism of action of asenapine, in schizophrenia and bipolar I disorder, is unknown. It has been suggested that the efficacy of asenapine in schizophrenia could be mediated through a combination of antagonist activity at D 2 and 5-HT 2A receptors.

📦 How Supplied / Storage and Handling 185 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING SAPHRIS (asenapine) sublingual tablets are supplied as: 2.5 mg Tablets, black cherry flavor Round, white to off-white sublingual tablets, with a hexagon on one side. Child-resistant packaging Box of 60 6 blisters with 10 tablets NDC 0456-2402-60 Hospital Unit Dose Box of 100 10 blisters with 10 tablets NDC 0456-2402-63 5 mg Tablets, black cherry flavor Round, white to off-white sublingual tablets, with “5” on one side within a circle. Child-resistant packaging Box of 60 6 blisters with 10 tablets NDC 0456-2405-60 Hospital Unit Dose Box of 100 10 blisters with 10 tablets NDC 0456-2405-63 10 mg Tablets, black cherry flavor Round, white to off-white sublingual tablets, with “10” on one side within a circle.

Child-resistant packaging Box of 60 6 blisters with 10 tablets NDC 0456-2410-60 Hospital Unit Dose Box of 100 10 blisters with 10 tablets NDC 0456-2410-63 Storage Store at 20 º C to 25 º C (68 º F to 77 º F) ; excursions permitted between 15 º C and 30 º C (59 º F and 86 º F) [see USP Controlled Room Temperature].

📋 Description 153 words ▾

11 DESCRIPTION SAPHRIS contains asenapine maleate which is an atypical antipsychotic that is available for sublingual administration. Asenapine belongs to the class dibenzo-oxepino pyrroles. The chemical designation is (3a RS ,12b RS )-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1 H dibenzo[2,3:6,7]oxepino[4,5- c ]pyrrole (2 Z )-2-butenedioate (1:1).

Its molecular formula is C 17 H 16 ClNO•C 4 H 4 O 4 and its molecular weight is 401.84 (free base: 285.8). The chemical structure is: Asenapine maleate is a white to off-white powder. SAPHRIS, black cherry flavor, is supplied for sublingual administration in tablets containing 2.5 mg, 5 mg or 10 mg asenapine; inactive ingredients include gelatin, mannitol, sucralose, and black cherry flavor.

SAPHRIS contains asenapine maleate which is an atypical antipsychotic that is available for sublingual administration. Asenapine belongs to the class dibenzo-oxepino pyrroles. The chemical designation is (3aRS,12bRS)-5-Chloro-2-methyl-2,3,3a,12b-tetrahydro-1Hdibenzo[2,3:6,7]oxepino[4,5-c]pyrrole (2Z)-2-butenedioate (1:1).

Its molecular formula is C17H16ClNOC4H4O4 and its molecular weight is 401.84 (free base: 285.8). The chemical structure is:

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Instructions for Use ). Dosage and Administration Counsel patients on proper sublingual administration of SAPHRIS and advise them to read the FDA-approved patient labeling ( Instructions for Use ). When initiating treatment with SAPHRIS, provide dosage escalation instructions [see Dosage and Administration ( 2 )].

Hypersensitivity Reactions Counsel patients on the signs and symptoms of a serious allergic reaction (e.g., difficulty breathing, itching, swelling of the face, tongue or throat, feeling lightheaded etc.) and to seek immediate emergency assistance if they develop any of these signs and symptoms [see Contraindications ( 4 ), Warnings and Precautions ( 5.6 ) and Adverse Reactions ( 6 )] . Application Site Reactions Inform patients that application site reactions, primarily in the sublingual area, including oral ulcers, blisters, peeling/sloughing and inflammation have been reported.

Instruct patients to monitor for these reactions [see Adverse Reactions ( 6.2 )] . Inform patients that numbness or tingling of the mouth or throat may occur directly after administration of SAPHRIS and usually resolves within 1 hour [ see Adverse R eactions ( 6.1 ) ] . Neuroleptic Malignant Syndrome Counsel patients about a potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) that has been reported in association with administration of antipsychotic drugs.

Patients should contact their health care provider or report to the emergency room if they experience the following signs and symptoms of NMS, including hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see Warnings and Precautions ( 5.3 )] . Tardive Dyskinesia Counsel patients on the signs and symptoms of tardive dyskinesia and to contact their health care provider if these abnormal movements occur [ see Warnings and Precautions ( 5.4 ) ] .

Metabolic Changes ( Hyperglycemia and Diabetes Mellitus , Dyslipidemia, and Weight Gain) Educate patients about the risk of metabolic changes, how to recognize symptoms of hyperglycemia (high blood sugar) and diabetes mellitus, and the need for specific monitoring, including blood glucose, lipids, and weight [see Warnings and Precautions ( 5.5 )]. Orthostatic Hypotension Educate patients about the risk of orthostatic hypotension (symptoms include feeling dizzy or lightheaded upon standing) especially early in treatment, and also at times of re-initiating treatment or increases in dose [ see Warnings and Precautions ( 5.7 ) ] .

Leukopenia/Neutropenia Advise patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia they should have their CBC monitored while taking SAPHRIS [s ee Warnings and Precautions ( 5.9 )] . H yperprolactinemia Counsel patients on the signs and symptoms of hyperprolactinemia and to contact their health care provider if these abnormalities occur [ see Warnings and Precautions ( 5.11 ) ] . Interference with Cognitive and Motor Performance Caution patients about performing activities requiring mental alertness, such as operating hazardous machinery or operating a motor vehicle, until they are reasonably certain that SAPHRIS therapy does not affect them adversely [see Warnings and Precautions ( 5.13 )] .

Heat Exposure and Dehydration Counsel patients regarding appropriate care in avoiding overheating and dehydration [see Warnings and Precautions ( 5.14 )] . Concomitant Medication s Advise patients to inform their health care provider if they are taking, or plan to take, any prescription or over-the-counter medications since there is a potential for interactions [see Drug Interactions ( 7.1 )] . Pregnancy Advise patients that SAPHRIS may cause fetal harm as well as extrapyramidal and/or withdrawal symptoms in a neonate.

Advise patients to n…

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