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Relexxii methylphenidate hydrochloride 72 mg Tablet, Extended Release, 30-count — NDC 68025-0084-30 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Relexxii methylphenidate hydrochloride 72 mg Tablet, Extended Release, 30-count — NDC 68025-084-30 (Billing 68025-0084-30)

by Vertical Pharmaceuticals, LLC · 30 TABLET, EXTENDED RELEASE in 1 BOTTLE

This is a package of 30 tablets of Relexxii methylphenidate hydrochloride 72 mg Tablet, Extended Release from Vertical Pharmaceuticals, LLC, marketed since Jun 2022 and currently FDA-listed; retail pharmacies pay about $22.10 per tablet (NADAC). It is the main listing for this product, which comes in 2 package sizes.

NDC 68025-0084-30
🏷️ FDA NDC (as labeled) 68025-084-30 billing pads the product segment with a zero
This package
Contains30-count Cost per ea$22.10 NADAC Per package$662.98 / 30 tablets Pack sizes2 compare ↓
Also priced by: Medicaid pays $22.31/unit · Part D plans $23.46/unit — full pricing hub ↓
Main listing for product 68025-084 · Also comes in: 100 tablets 68025-084-10
Rx only Brand On market CII ⚠ On shortage ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed 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

⚠️
Active FDA shortage. Methylphenidate Hydrochloride Tablet, Extended Release is currently reported in shortage by the FDA. Available Shortage details →
⚠️
Other active recalls for Methylphenidate Hydrochloride (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Feb 7, 2022 — Failed Tablet Specifications: Recall of this drug product was voluntarily initiated by the manufacturer due to a market complaint, which stated that a tablet in the sealed bottle was twice larger in size when compared to the remaining tablets. This complaint is second of its kind. (RISING PHARMACEUTICALS) · FDA recall D-0573-2022
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 68025-084-30
Product NDC 68025-084
11-digit billing NDC 68025008430
NCPDP billing unit EA — each (per item)
RxCUI 1091155, 1091170, 1091185, 1091210, 1995461, 2052826, 2605796, 2605798,
UNII 4B3SC438HI
UPC 0368025097109, 0368025096300, 0368025096102, 0368025084307 +7 more
Application # NDA216117
SPL Set ID 22d5fa47-b5b9-4fd9-980c-4eb88e95ae5d
Established class (EPC) Central Nervous System Stimulant
Physiologic effect Central Nervous System Stimulation
DEA schedule CII
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-06-23
Route ORAL
Dosage form TABLET, EXTENDED RELEASE
Substance METHYLPHENIDATE HYDROCHLORIDE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 61400020100490
GPI class Relexxii
GCN Seq No 078038
GCN 44239
HICL code 001682
Ingredient (HICL) Methylphenidate Hcl
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H2
Therapeutic class — intermediate (HIC2) Psychoactive Drugs
HIC3 code H2V
Therapeutic class — specific (HIC3) Tx For Attention Deficit-Hyperact(Adhd)/Narcolepsy
AHFS code 28:20.32.00
AHFS class Respiratory And Cns Stimulants
FDB label name RELEXXII ER 72 MG TABLET
FDB brand name Relexxii
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 078038
  • GCN: 44239
  • GPI-14 (Medi-Span): 61400020100490
  • HICL (First Databank): 001682
  • AHFS class code: 28:20.32.00
  • RxCUI (RxNorm): 1091155
Why two NDCs? The FDA registers this code as 68025-084-30 — a 5-3-2 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 product segment → 68025-0084-30. 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 Central Nervous System Stimulant class.

Pharmacologic class Central Nervous System Stimulant
Drug family (ATC) Centrally acting sympathomimetics
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.

Clinical

Label name RELEXXII ER 72 MG TABLET Ingredient Methylphenidate Hcl
📖 What it is MedlinePlus · NLM

Methylphenidate is used to control symptoms of attention deficit hyperactivity disorder (ADHD; condition that makes it hard to pay attention, control your behavior, and remain still or quiet) and to treat narcolepsy (condition that causes people to be very sleepy during the day and to fall asleep suddenly). Methylphenidate is in a class of medications called central nervous system (CNS) stimulants. It works by changing the amounts of certain natural substances in the brain.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It mainly treats ADHD, and some products are also used for narcolepsy. The exact approval depends on the product and the age group. Your prescriber chooses the right one for you.
  • It depends on your product. Many extended-release forms are taken once daily in the morning, while Jornay PM is taken in the evening. Swallow extended-release tablets whole, and fo...
  • The most common ones are decreased appetite, headache, dry mouth, nausea, trouble sleeping, anxiety and dizziness. Children and teens may get upper stomach pain. Call your doctor i...
  • Call for chest pain, fainting, a racing heartbeat, hallucinations, seizures, painful erections that won’t go away, or color changes in your fingers or toes. Also call if you notice...
📖 Read our full Methylphenidate 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.

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 $22.099 $662.98 / 30 tablets
Medicaid paysCMS SDUD · 12 mo $22.31 $669.35 / 30 tablets
Medicare drug plans payPart D · Q2 2026 $23.46 $703.78 / 30 tablets
NADAC price history (per ea) — tap or hover for the price & month
Jul 2026 Aug 2026 Sep 2026 $22.099 $22.099
Flat over the last 3 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.

Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startMarketing endStatus
68025-0084-10 68025-084-10 100 TABLET, EXTENDED RELEASE in 1 BOTTLE — — 2018-11-08 — Active
68025-0084-30 You're viewing this Main listing 30 TABLET, EXTENDED RELEASE in 1 BOTTLE $22.10 / ea $662.98 2019-04-01 — Active

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

Pack size FAQ

What quantity is in this package?
This is a 30-count package — 30 tablet, extended release in 1 bottle.
How does this package differ from NDC 68025-0084-10?
Both are Relexxii methylphenidate hydrochloride 72 mg Tablet, Extended Release — the drug itself is identical. This page's package is the 30-count one, while NDC 68025-0084-10 is the 100 tablets package.
What NDC number is used to bill for this package of Relexxii methylphenidate hydrochloride 72 mg Tablet, Extended Release?
Use the 11-digit billing form listed in the identifiers section of this page. 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.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Methylphenidate Hydrochloride 72 mg 57664-0710-83 Sun 30 tablets $16.509 AB Availability likely save 25%
Methylphenidate Hydrochloride 72 mg 72603-0399-01 Northstar 30 tablets $16.509 AB Availability likely save 25%
Relexxii 72 mgthis 68025-0084-30 Vertical 30 tablets $22.099 — Availability likely —
Methylphenidate Hydrochloride 72 mg 13811-0710-10 Trigen 100 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

🏛️
2022
First FDA approval
Jun 2022
📍
2026
Currently FDA-listed
4 years listed
🛡️
2037
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 Feb 2037. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Jun 23, 2022 RLD RS ⏳ ~10.3 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 10695336 — method of use (U-4032)
US 10695336 — method of use (U-4032)
US 10695336 — method of use (U-4032)
US 10695336 — method of use (U-4032)
US 10695336 — method of use (U-4032)
US 10695336 — method of use (U-4032)
US 10695336 — method of use (U-4032)
US 10265308 — method of use (U-4032)
US 10265308 — method of use (U-4032)
US 10265308 — method of use (U-4032)
US 10265308 — method of use (U-4032)
US 10265308 — method of use (U-4032)
US 10265308 — method of use (U-4032)
US 10265308 — method of use (U-4032)
US 9855258 — method of use (U-4032)
US 9855258 — method of use (U-4032)
US 9855258 — method of use (U-4032)
US 9855258 — method of use (U-4032)
US 9855258 — method of use (U-4032)
US 9855258 — method of use (U-4032)
US 9855258 — method of use (U-4032)
US 9827234 — method of use (U-4032)
US 9827234 — method of use (U-4032)
US 9827234 — method of use (U-4032)
US 9827234 — method of use (U-4032)
US 9827234 — method of use (U-4032)
US 9827234 — method of use (U-4032)
US 9827234 — method of use (U-4032)
US 9707217 — drug product
US 9707217 — drug product
US 9707217 — drug product
US 9707217 — drug product
US 9707217 — drug product
US 9707217 — drug product
US 9707217 — drug product
2022 2024 2026 2028 2030 2032 2034 2036
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 (35)
PatentTypeUse codeExpires
US 10695336 ↗ Method of use U-4032 Feb 3, 2037
US 10695336 ↗ Method of use U-4032 Feb 3, 2037
US 10695336 ↗ Method of use U-4032 Feb 3, 2037
US 10695336 ↗ Method of use U-4032 Feb 3, 2037
US 10695336 ↗ Method of use U-4032 Feb 3, 2037
US 10695336 ↗ Method of use U-4032 Feb 3, 2037
US 10695336 ↗ Method of use U-4032 Feb 3, 2037
US 10265308 ↗ Method of use U-4032 Feb 3, 2037
US 10265308 ↗ Method of use U-4032 Feb 3, 2037
US 10265308 ↗ Method of use U-4032 Feb 3, 2037
US 10265308 ↗ Method of use U-4032 Feb 3, 2037
US 10265308 ↗ Method of use U-4032 Feb 3, 2037
US 10265308 ↗ Method of use U-4032 Feb 3, 2037
US 10265308 ↗ Method of use U-4032 Feb 3, 2037
US 9855258 ↗ Method of use U-4032 Feb 3, 2037
US 9855258 ↗ Method of use U-4032 Feb 3, 2037
US 9855258 ↗ Method of use U-4032 Feb 3, 2037
US 9855258 ↗ Method of use U-4032 Feb 3, 2037
US 9855258 ↗ Method of use U-4032 Feb 3, 2037
US 9855258 ↗ Method of use U-4032 Feb 3, 2037
US 9855258 ↗ Method of use U-4032 Feb 3, 2037
US 9827234 ↗ Method of use U-4032 Feb 3, 2037
US 9827234 ↗ Method of use U-4032 Feb 3, 2037
US 9827234 ↗ Method of use U-4032 Feb 3, 2037
US 9827234 ↗ Method of use U-4032 Feb 3, 2037
US 9827234 ↗ Method of use U-4032 Feb 3, 2037
US 9827234 ↗ Method of use U-4032 Feb 3, 2037
US 9827234 ↗ Method of use U-4032 Feb 3, 2037
US 9707217 ↗ Drug product — Feb 3, 2037
US 9707217 ↗ Drug product — Feb 3, 2037
US 9707217 ↗ Drug product — Feb 3, 2037
US 9707217 ↗ Drug product — Feb 3, 2037
US 9707217 ↗ Drug product — Feb 3, 2037
US 9707217 ↗ Drug product — Feb 3, 2037
US 9707217 ↗ Drug product — Feb 3, 2037
Common questions
Is there a generic version of RELEXXII ER 72 MG TABLET?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for RELEXXII ER 72 MG TABLET. 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.

What it looks like

Color pink / orange / yellow / gray / white / blue
ShapeRound
ImprintTL709
Size8 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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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.

Manufacturer & labeler

LabelerVertical Pharmaceuticals, LLC
Application holderOSMOTICA PHARMACEUTICAL US LLC
FDA applicationNDA216117 (NDA)
Labeler code68025
First marketedJun 2022
DEA scheduleCII
Product typeHuman Prescription Drug
Portfolio15 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.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). 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 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🔒 Drug Abuse and Dependence 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~1 min read ▾

WARNING: ABUSE, MISUSE, AND ADDICTION RELEXXII has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including RELEXXII, can result in overdose and death [see Overdosage ( 10 )] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing RELEXXII, assess each patient’s risk for abuse, misuse, and addiction.

Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout RELEXXII treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction [see Warnings and Precautions ( 5.1 ) and Drug Abuse and Dependence ( 9.2 )] . WARNING: ABUSE, MISUSE, AND ADDICTION See full prescribing information for complete boxed warning.

RELEXXII has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including RELEXXII, can result in overdose and death ( 5.1 , 9.2 , 10 ): Before prescribing RELEXXII, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug.

Throughout treatment, reassess each patient’s risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

🎯 Indications and Usage 192 words ▾

1 INDICATIONS AND USAGE RELEXXII is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults (up to the age of 65 years) and pediatric patients 6 years of age and older [ see Clinical Studies ( 14 )] . Limitations of Use The use of RELEXXII is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage [see Warnings and Precautions ( 5.7 ), Use in Specific Populations ( 8.4 )] .

RELEXXII ® is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults (up to the age of 65 years) and pediatric patients 6 years of age and older ( 1 ). Limitations of Use The use of RELEXXII is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage ( 5.7 , 8.4 ).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Administer once daily in the morning with or without food. ( 2.2 ) Swallow whole with liquid. Do not chew, divide, or crush.

( 2.2 ) Recommended dosage for patients new to methylphenidate ( 2.3 ): Pediatric patients 6 to 17 years Starting dosage is 18 mg once daily. Dosage may be increased by 18 mg once per day at weekly intervals. Maximum dosage for pediatric patients 6 to 12 years: 54 mg once daily.

Maximum dosage for pediatric patients 13 to 17 years: 72 mg once daily. Adults (up to 65 years) Starting dosage is 18 mg or 36 mg once daily. Dosage may be increased by 18 mg once daily at weekly intervals.

Maximum dosage: 72 mg once daily.

2.1Pretreatment Screening Prior to treating patients with RELEXXII, assess: for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions ( 5.2 )] . the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating RELEXXII [see Warnings and Precautions ( 5.11 )].

2.2General Administration Information Administer RELEXXII orally once daily in the morning with or without food. Swallow RELEXXII whole with liquid. Do not chew, divide, or crush [see Warnings and Precautions ( 5.8 )] .

2.3Dosage Recommendations for Patients New to Methylphenidate Table 1 includes the starting dosage and dosage recommendations for RELEXXII in pediatric patients 6 to 17 years and adults who are not currently taking methylphenidate or other stimulants. Table 1: Dosage Recommendations for RELEXXII in Pediatric Patients 6 to 17 years and Adults Patient Population RELEXXII Recommended Starting Dosage RELEXXII Dosage Range Pediatric patients 6 to 12 years 18 mg once daily 18 mg to 54 mg once daily 13 to 17 years 18 mg once daily 18 mg to 72 mg once daily (not to exceed 2 mg/kg/day) Adults 18 (up to 65 years) 18 mg or 36 mg once daily 18 mg to 72 mg once daily

2.4Dosage Recommendations for Patients Currently Using Methylphenidate The recommended starting dosage of RELEXXII for patients who are currently taking methylphenidate twice daily or three times daily at doses of 10 mg to 60 mg daily is provided in Table 2. Table 2: Recommended Starting Dosage when Converting from Methylphenidate Regimens to RELEXXII Current Methylphenidate Daily Dosage Recommended Starting Dosage of RELEXXII 5 mg methylphenidate twice daily or three times daily 18 mg once daily in the morning 10 mg methylphenidate twice daily or three times daily 36 mg once daily in the morning 15 mg methylphenidate twice daily or three times daily 54 mg once daily in the morning 20 mg methylphenidate twice daily or three times daily 72 mg once daily in the morning

2.5Dose Titration Doses may be increased in 18 mg increments at weekly intervals for patients who have not achieved clinical response at a lower dose. Daily dosages above 54 mg in pediatric patients 6 to 12 years and above 72 mg in pediatric patients 13 to 17 years have not been studied and are not recommended. Daily dosages above 72 mg are not recommended in adults.

Dosage strengths of 27 mg, 45 mg, and 63 mg are available for additional titration options based on clinical response.

2.6Dosage Reduction and Discontinuation If paradoxical aggravation of symptoms or other adverse reaction occur, reduce the dosage, or, if necessary, discontinue RELEXXII. If improvement is not observed after appropriate dosage adjustment over a one-month period, discontinue RELEXXII.

💊 Dosage Forms and Strengths 99 words ▾

3 DOSAGE FORMS AND STRENGTHS RELEXXII (methylphenidate hydrochloride extended-release tablets) are available in the following strengths: 18 mg: yellow with “TL706” imprinted in black ink 27 mg: gray with “TL707” imprinted in black ink 36 mg: white with “TL708” imprinted in black ink 45 mg: pink with “TL711” imprinted in black ink 54 mg: pink with “TL709” imprinted in black ink 63 mg: orange with “TL700” imprinted in black ink and 72 mg: blue with “TL710” imprinted in black ink. Extended-release tablets:18 mg, 27 mg, 36 mg, 45 mg, 54 mg, 63 mg, and 72 mg ( 3 )

⛔ Contraindications 110 words ▾

4 CONTRAINDICATIONS RELEXXII is contraindicated in patients: with a known hypersensitivity to methylphenidate or other components of RELEXXII. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other methylphenidate products [see Adverse Reactions ( 6.2 )] . receiving concomitant treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with a MAOI, because of the risk of hypertensive crisis [see Drug Interactions ( 7.1 )] .

Known hypersensitivity to methylphenidate or other components of RELEXXII ( 4 ) Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or serious cardiac disease. ( 5.2 ) Increased Blood Pressure and Heart Rate: Monitor blood pressure and pulse. ( 5.3 ) Psychiatric Adverse Reactions: Prior to initiating RELEXXII, screen patients for risk factors for developing a manic episode.

If new psychotic or manic symptoms occur, consider discontinuing RELEXXII. ( 5.4 ) Priapism: If abnormally sustained or frequent and painful erections occur, patients should seek immediate medical attention. ( 5.5 ) Peripheral Vasculopathy, including Raynaud’s Phenomenon: Careful observation for digital changes is necessary during RELEXXII treatment.

Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy. ( 5.6 ) Long-Term Suppression of Growth in Pediatric Patients: Closely monitor growth (height and weight) in pediatric patients. Pediatric patients not growing or gaining weight as expected may need to have their treatment interrupted.

( 5.7 ) Gastrointestinal Obstruction: Avoid use with preexisting GI narrowing. ( 5.8 ) Acute Angle Closure Glaucoma: RELEXXII-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist. ( 5.9 ) Increased Intraocular Pressure (IOP) and Glaucoma: Prescribe RELEXXII to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk.

Closely monitor patients with a history of increased IOP or open angle glaucoma. ( 5.10 ) Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: Before initiating RELEXXII, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome.

Discontinue treatment if clinically appropriate. ( 5.11 )

5.1Abuse, Misuse, and Addiction RELEXXII has a high potential for abuse and misuse. The use of RELEXXII exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. RELEXXII can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence ( 9.2 , 9.3 )].

Misuse and abuse of CNS stimulants, including RELEXXII, can result in overdose and death [see Overdosage ( 10 )] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing RELEXXII, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug.

Advise patients to store RELEXXII in a safe place, preferably locked, and instruct patients to not give RELEXXII to anyone else. Throughout RELEXXII treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

5.2Risks to Patients with Serious Cardiac Disease Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were taking CNS stimulants at the recommended ADHD dosage. Avoid RELEXXII use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.

5.3Increased Blood Pressure and Heart Rate CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mm Hg) and heart rate (mean increase approximately 3 to 6 bpm) [see Adverse Reactions ( 6.1 )]. Some patients may have larger increases. Monitor all RELEXXII-treated patients for hypertension and tachycardia.

5.4Psychiatric Adverse Reactions Exacerbation of Pre-exi… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Box Warning, Warnings and Precautions ( 5.1 ), and Drug Abuse and Dependence ( 9.2 , 9.3 )] Known hypersensitivity to methylphenidate or other ingredients [see Contraindications ( 4 )] Hypertensive crisis when used concomitantly with monoamine oxidase inhibitors [see Contraindications (4) and Drug Interactions ( 7.1 )] Risks to Patients with Serious Cardiac Disease [see Warnings and Precautions ( 5.2 )] Increased Blood Pressure and Heart Rate [see Warnings and Precautions ( 5.3 )] Psychiatric Adverse Reactions [ see Warnings and Precautions ( 5.4 )] Priapism [see Warnings and Precautions ( 5.5 )] Peripheral Vasculopathy, including Raynaud’s Phenomenon [see Warnings and Precautions ( 5.6 )] Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions ( 5.7 )] Potential for Gastrointestinal Obstruction [see Warnings and Precautions ( 5.8 )] Acute Angle Closure Glaucoma [see Warnings and Precautions ( 5.9 )] Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions ( 5.10 )] Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions ( 5.11 )] The most common adverse reactions (>5%) were: Pediatric patients 6 to 17 years: abdominal pain upper ( 6.1 ) Adults: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vertical Pharmaceuticals, LLC at 1-800-444-5164 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 clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of RELEXXII for the treatment of ADHD is based on adequate and well-controlled studies of another formulation of methylphenidate hydrochloride extended-release tablets. Below is a display of adverse reactions from those adequate and well-controlled studies in ADHD.

Adults and pediatric patients 6 to 17 years with ADHD were evaluated in six controlled clinical studies and eleven open-label clinical studies (see Table 3). Safety was assessed by collecting adverse reactions, vital signs, weights, and electrocardiograms (ECGs), and by performing physical examinations and laboratory analyses. A total of 3,906 patients participated in the clinical trials.

Table 3: Exposure in Double-Blind and Open-Label Clinical Studies of Another Formulation of Methylphenidate Hydrochloride Extended-Release Tablets Patient Population N Dosage Range Pediatric patients 6 to 12 years 2216 18 mg to 54 mg once daily Pediatric patients 13 to 17 years 502 18 mg to 72 mg once daily Adults 1188 18 mg to 108 mg* once daily * 108 mg is 1.5 times the maximum recommended dosage of RELEXXII. The most common adverse reactions in double-blind clinical trials (>5%) were: Pediatric patients 6 to 17 years: abdominal pain upper (see Table 4).

Adults: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis (see Table 5). The most common adverse reactions associated with discontinuation (≥1%) from either pediatric or adult clinical trials were anxiety, irritability, insomnia, and blood pressure increased . Adverse reactions in either the pediatric or adult double-blind adverse reactions tables may be relevant for both patient populations.

Pediatric Patients 6 to 17 Years Table 4 lists the adverse reactions reported in 1% or more of another formulation of methylphenidate hydrochloride extended-release tablet-treated pediatric patients (6 to 17 years) in four placebo-controlled, double-blind clinical trials. Table 4: Adverse Reactions Reported by ≥1% of Pediatric Patient… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 215 words ▾

7 DRUG INTERACTIONS Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed ( 7.1 )

7.1Clinically Important Drug Interactions Table 6 presents clinically important drug interactions with RELEXXII. Table 6: Drugs Having Clinically Important Interactions with RELEXXII Monoamine Oxidase Inhibitors (MAOI) Clinical Impact: Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see Contraindications ( 4 )] .

Intervention: Do not administer RELEXXII concomitantly with MAOIs or within 14 days after discontinuing MAOI treatment. Antihypertensive Drugs Clinical Impact: RELEXXII may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions ( 5.3 )] . Intervention: Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed.

Halogenated Anesthetics Clinical Impact: Concomitant use of halogenated anesthetics and RELEXXII may increase the risk of sudden blood pressure and heart rate increase during surgery. Intervention: Avoid use of RELEXXII in patients being treated with anesthetics on the day of surgery. Risperidone Clinical Impact: Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS).

Intervention: Monitor for signs of EPS.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including RELEXXII, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388. Risk Summary Published studies and post-marketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

There are risks to the fetus associated with the use of central nervous system (CNS) stimulants during pregnancy ( see Clinical Considerations). No effects on morphological development were observed in development studies with oral administration of methylphenidate to pregnant rats at doses up to 4 times the maximum recommended human dose (MRHD) of 72 mg/day given to adults on a mg/m 2 basis. However, malformations were observed in rabbits at a dose 54 times the MRHD given to adults.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Clinical Considerations Fetal/Neonatal Adverse Reactions CNS stimulants, such as RELEXXII, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine‑dependent mothers. Data Animal Data In development studies conducted in rats and rabbits, methylphenidate was administered at doses up to 30 and 200 mg/kg/day, respectively.

Methylphenidate has been shown to cause malformations in rabbits when given in doses of 200 mg/kg/day, which is approximately 54 times the MRHD on a mg/m 2 basis, respectively. A reproduction study in rats revealed no evidence of harm to the fetus at oral doses up to 30 mg/kg/day, approximately 4-fold the MRHD on a mg/m 2 basis.

8.2Lactation Risk Summary Limited published literature, based on breast milk sampling from five mothers, reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7. There are no reports of adverse effects on the breastfed infant and no effects on milk production. However, long‑term neurodevelopmental effects on infants from CNS stimulant exposure are unknown.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for RELEXXII and any potential adverse effects on the breastfed infant from RELEXXII or from the underlying maternal condition. Clinical Considerations Monitor breastfeeding infants for adverse reactions, such as agitation, anorexia, and reduced weight gain.

8.4Pediatric Use The safety and effectiveness of RELEXXII have not been established in pediatric patients below the age of 6 years. In studies evaluating extended-release methylphenidate products, patients 4 to <6 years of age had higher systemic methylphenidate exposures than those observed in older pediatric patients at the same dosage. Pediatric patients 4 to <6 years of age also had a higher incidence of adverse reactions, including weight loss.

The safety and effectiveness of RELEXXII for the treatment of ADHD have been established in pediatric patients 6 to 17 years. Long Term Suppression of Growth Growth should be monitored during treatment with stimulants, including RELEXXII. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment in… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including RELEXXII, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388. Risk Summary Published studies and post-marketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

There are risks to the fetus associated with the use of central nervous system (CNS) stimulants during pregnancy ( see Clinical Considerations). No effects on morphological development were observed in development studies with oral administration of methylphenidate to pregnant rats at doses up to 4 times the maximum recommended human dose (MRHD) of 72 mg/day given to adults on a mg/m 2 basis. However, malformations were observed in rabbits at a dose 54 times the MRHD given to adults.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Clinical Considerations Fetal/Neonatal Adverse Reactions CNS stimulants, such as RELEXXII, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine‑dependent mothers. Data Animal Data In development studies conducted in rats and rabbits, methylphenidate was administered at doses up to 30 and 200 mg/kg/day, respectively.

Methylphenidate has been shown to cause malformations in rabbits when given in doses of 200 mg/kg/day, which is approximately 54 times the MRHD on a mg/m 2 basis, respectively. A reproduction study in rats revealed no evidence of harm to the fetus at oral doses up to 30 mg/kg/day, approximately 4-fold the MRHD on a mg/m 2 basis.

🧒 Pediatric Use ~1 min read ▾

8.4Pediatric Use The safety and effectiveness of RELEXXII have not been established in pediatric patients below the age of 6 years. In studies evaluating extended-release methylphenidate products, patients 4 to <6 years of age had higher systemic methylphenidate exposures than those observed in older pediatric patients at the same dosage. Pediatric patients 4 to <6 years of age also had a higher incidence of adverse reactions, including weight loss.

The safety and effectiveness of RELEXXII for the treatment of ADHD have been established in pediatric patients 6 to 17 years. Long Term Suppression of Growth Growth should be monitored during treatment with stimulants, including RELEXXII. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions ( 5.7 ) and Adverse Reactions ( 6.1 )] .

Juvenile Animal Toxicity Data In the study conducted in young rats, methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (postnatal day 7) and continuing through sexual maturity (postnatal week 10). When these animals were tested as adults (postnatal weeks 13-14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 4 times the MRHD of 54 mg/day given to children on a mg/m 2 basis) or greater, and a deficit in the acquisition of a specific learning task was observed in females exposed to the highest dose (9 times the MRHD given to children on a mg/m 2 basis).

The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (equal to the MRHD given to children on a mg/m 2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.

🧓 Geriatric Use 16 words ▾

8.5Geriatric Use RELEXXII has not been studied in patients greater than 65 years of age.

🆘 Overdosage 122 words ▾

10 OVERDOSAGE Clinical Effects of Overdose Overdose of CNS stimulants is characterized by the following sympathomimetic effects: Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop.

CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur. Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop.

Overdose Management Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of RELEXXII should be considered when treating patients with overdose. Because methylphenidate has a large volume of distribution and is rapidly metabolized, dialysis is not useful.

Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Methylphenidate HCl is a CNS stimulant. The mode of therapeutic action in ADHD is not known.

12.2Pharmacodynamics Methylphenidate is a racemic mixture comprised of the d- and l-threo entantiomers. The d-threo enantiomer is more pharmacologically active than the l-threo enantiomer. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

12.3Pharmacokinetics In a relative bioavailability study in healthy adults under fasted conditions, plasma exposures of 72 mg RELEXXII and 72 mg (2 x 36 mg) methylphenidate extended-release tablets were compared. The peak plasma concentration (C max ) of RELEXXII and methylphenidate extended-release tablets is 19.7 ng/mL and 19.3 ng/mL, respectively. The area under the plasma concentration-time curve (AUC 0-inf ) of RELEXXII and methylphenidate extended-release tablets is 206.1 ng∙h/mL and 200.9 ng∙h/mL, respectively.

Absorption Methylphenidate is readily absorbed. Following oral administration of RELEXXII plasma methylphenidate concentrations increase rapidly, reaching an initial maximum at about 1.5 hour, followed by gradual ascending concentrations over the next 5 to 6 hours, after which a gradual decrease begins. Mean time to reach peak plasma concentrations of RELEXXII occurs at 5.5 hours.

Methylphenidate hydrochloride extended-release tablets once daily minimizes the fluctuations between peak and trough concentrations associated with immediate-release methylphenidate three times daily. Figure 1 displays mean plasma exposures of methylphenidate hydrochloride extended-release tablets once daily and methylphenidate three times daily (administered every 4 hours) in adults. Figure 1: Mean Methylphenidate Plasma Concentration-Time Profiles The mean single-dose pharmacokinetic parameters in 36 healthy adults following the administration of methylphenidate hydrochloride extended-release tablets 18 mg once daily and methylphenidate 5 mg three times daily are summarized in Table 7.

Table 7: Methylphenidate Pharmacokinetic Parameters (Mean ± SD) After Single Dose in Healthy Adults Parameters Methylphenidate Hydrochloride Extended-release Tablets (18 mg once daily) (n=36) Methylphenidate (5 mg three times daily) (n=35) C max (ng/mL) 3.7 ± 1.0 4.2 ±

1.0T max (h) 6.8 ± 1.8 6.5 ±

1.8AUC inf (ng∙h/mL) 41.8 ± 13.9 38.0 ± 11.0 t 1/2 (h) 3.5 ± 0.4 3.0 ±

0.5The pharmacokinetics of methylphenidate hydrochloride extended-release tablets were evaluated in healthy adults following single- and multiple-dose administration (steady state) of doses up to 144 mg per day (2 times the maximum recommended daily dosage of methylphenidate hydrochloride extended-release tablets). The mean half-life was about 3.6 hours. No differences in the pharmacokinetics of methylphenidate hydrochloride extended-release tablets were noted following single and repeated once-daily dosing, indicating no significant drug accumulation.

The AUC and t 1/2 following repeated once-daily dosing are similar to those following the first dose of methylphenidate hydrochloride extended-release tablets in a dose range of 18 mg to 144 mg. Effect of Food There were no differences in either the pharmacokinetics or the pharmacodynamic performance of methylphenidate hydrochloride extended-release tablets when administered after a high-fat breakfast. There is no evidence of dose dumping in the presence or absence of food.

Effect of Alcohol In-vitr o studies were conducted to explore the effect of alcohol on the release characteristics of methylphenidate from RELEXXII. At alcohol concentrations up to 40%, there was no increased release of methylphenidate in the first two hours. Dose Proportionality Following administration methylphenidate hydrochloride extended-release tablets in single doses of 18 mg, 36 mg, and 54 mg per day to healthy adults, C max and AUC (0–inf) of d-methylphenidate were p… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 20 words ▾

12.1Mechanism of Action Methylphenidate HCl is a CNS stimulant. The mode of therapeutic action in ADHD is not known.

📦 How Supplied / Storage and Handling 169 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied RELEXXII ® (methylphenidate hydrochloride extended-release tablets) are available as: 18 mg yellow tablets with "TL706" imprinted in black ink NDC 68025-095-30 in 30-count bottle NDC 68025-095-10 in 100-count bottle 27 mg gray tablets with "TL707" imprinted in black ink NDC 68025-096-30 in 30-count bottle NDC 68025-096-10 in 100-count bottle 36 mg white tablets with "TL708" imprinted in black ink NDC 68025-097-30 in 30-count bottle NDC 68025-097-10 in 100-count bottle 45 mg pink tablets with "TL711" imprinted in black ink NDC 68025-088-30 in 30-count bottle 54 mg pink tablets with "TL709" imprinted in black ink NDC 68025-098-30 in 30-count bottle NDC 68025-098-10 in 100-count bottle 63 mg orange tablets with "TL700" imprinted in black ink NDC 68025-089-30 in 30-count bottle 72 mg blue tablets with "TL710" imprinted in black ink NDC 68025-084-30 in 30-count bottle Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Protect from humidity.

📋 Description ~2 min read ▾

11 DESCRIPTION RELEXXII contains methylphenidate, a CNS stimulant, present as methylphenidate hydrochloride salt. Chemically, methylphenidate hydrochloride is d,l (racemic) methyl α-phenyl-2-piperidineacetate hydrochloride. Its empirical formula is C 14 H 19 NO 2 •HCl.

Its structural formula is: Methylphenidate hydrochloride is a white, odorless crystalline powder. Its solutions are acid to litmus. It is freely soluble in water and in methanol, soluble in alcohol, and slightly soluble in chloroform and in acetone.

It has a pKa of 8.71 (at 21.5°C). Its molecular weight is 269.77. RELEXXII is for oral administration and is available in the following strengths: 18 mg, 27 mg, 36 mg, 45 mg, 54 mg, 63 mg, and 72 mg containing methylphenidate hydrochloride (equivalent to 15.6 mg, 23.4 mg, 31.1 mg, 38.9 mg, 46.7 mg, 54.5 mg, and 62.3 mg methylphenidate respectively).

RELEXXII contains the following inactive ingredients: cellulose acetate, colloidal silicon dioxide, ferrosoferric oxide, hypromellose, iron oxide black, lactose monohydrate, magnesium stearate, phosphoric acid, polyethylene glycol, polyethylene oxide, sodium chloride, succinic acid, titanium dioxide, triacetin. RELEXXII also contains the following color additives: 27 mg: FD&C Yellow #6 Aluminum Lake, FD&C Blue #2 Aluminum Lake, FD&C Red #40 Aluminum Lake 45 mg: FD&C Red #40 Aluminum Lake 54 mg: FD&C Yellow #6 Aluminum Lake, FD&C Red #40 Aluminum Lake, FD&C Blue #2 Aluminum Lake 18 and 63 mg: iron oxide red, iron oxide yellow 72 mg: FD&C Blue #1 Aluminum Lake System Components and Performance RELEXXII uses osmotic pressure to deliver methylphenidate hydrochloride at a controlled rate.

The system, which resembles a conventional tablet in appearance, comprises an osmotically active bilayer core surrounded by a semipermeable membrane with an immediate-release drug overcoat. The bilayer core is composed of a drug layer containing the drug and excipients, and a push layer containing osmotically active components. There is a precision-laser drilled orifice on the drug-layer end of the tablet.

In an aqueous environment, such as the gastrointestinal tract, the drug overcoat dissolves within one hour, providing an initial dose of methylphenidate. Water permeates through the membrane into the tablet core. As the osmotically active polymer excipients expand, methylphenidate is released through the orifice.

The membrane controls the rate at which water enters the tablet core, which in turn controls drug delivery. Furthermore, the drug release rate from the system increases with time over a period of 6 to 7 hours due to the drug-concentration gradient incorporated into the two drug layers of core of RELEXXII. The biologically inert components of the tablet remain intact during gastrointestinal transit and are eliminated in the stool as a tablet shell along with insoluble core components.

It is possible that RELEXXII may be visible on abdominal x-rays under certain circumstances, especially when digital enhancing techniques are utilized. RELEXXII Structural Formula

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Abuse, Misuse, and Addiction Educate patients and their families about the risks of abuse, misuse, and addiction of RELEXXII, which can lead to overdose and death, and proper disposal of any unused drug [see Warnings and Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 ), and Overdosage ( 10 )] . Advise patients to store RELEXXII in a safe place, preferably locked, and instruct patients to not give RELEXXII to anyone else.

Administration Instructions Instruct patients to swallow RELEXXII whole with the aid of liquids, and not to chew, divide, or crush the tablets. Advise patients that the medication is contained within a nonabsorbable shell designed to release the drug at a controlled rate. The tablet shell, along with insoluble core components, is eliminated from the body; advise patients not to be concerned if they occasionally notice in their stool something that looks like a tablet [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.8 )] .

Risks to Patients with Serious Cardiac Disease Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death with RELEXXII use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see Warnings and Precautions ( 5.2 )] . Increased Blood Pressure and Heart Rate Advise patients and their caregivers that RELEXXII can cause elevations of their blood pressure and pulse rate [see Warnings and Precautions ( 5.3 )] .

Psychiatric Adverse Reactions Advise patients and their caregivers that RELEXXII, at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania [see Warnings and Precautions ( 5.4 )] . Priapism Advise patients, caregivers, and family members of the possibility of painful or prolonged penile erections (priapism). Instruct the patient to seek immediate medical attention in the event of priapism [see Warnings and Precautions ( 5.5 )] .

Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, including Raynaud’s Phenomenon] [see Warnings and Precautions ( 5.6 )] . Instruct patients beginning treatment with RELEXXII about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red. Instruct patients to report to their healthcare provider any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.

Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking RELEXXII. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. Long-Term Suppression of Growth in Pediatric Patients Advise patients, families and caregivers that RELEXXII may cause slowing of growth and weight loss [see Warnings and Precautions ( 5.7 )] .

Increased Intraocular Pressure (IOP) and Glaucoma Advise patients that IOP and glaucoma may occur during treatment with RELEXXII [see Warnings and Precautions ( 5.10 )] . Motor and Verbal Tics, and Worsening of Tourette’s Syndrome Advise patients that motor and verbal tics and worsening of Tourette’s Syndrome may occur during treatment with RELEXXII. Instruct patients to notify their healthcare provider if emergence of new tics or worsening of tics or Tourette’s syndrome occurs [see Warnings and Precautions ( 5.11 ] .

Pregnancy Registry Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to RELEXXII during pregnancy [see Use in Specific Populations ( 8.1 )] . Manufactured for: Vertical Pharmaceuticals, LLC Alpharetta, GA 30005 1-800-444-5164 www.v… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics In a relative bioavailability study in healthy adults under fasted conditions, plasma exposures of 72 mg RELEXXII and 72 mg (2 x 36 mg) methylphenidate extended-release tablets were compared. The peak plasma concentration (C max ) of RELEXXII and methylphenidate extended-release tablets is 19.7 ng/mL and 19.3 ng/mL, respectively. The area under the plasma concentration-time curve (AUC 0-inf ) of RELEXXII and methylphenidate extended-release tablets is 206.1 ng∙h/mL and 200.9 ng∙h/mL, respectively.

Absorption Methylphenidate is readily absorbed. Following oral administration of RELEXXII plasma methylphenidate concentrations increase rapidly, reaching an initial maximum at about 1.5 hour, followed by gradual ascending concentrations over the next 5 to 6 hours, after which a gradual decrease begins. Mean time to reach peak plasma concentrations of RELEXXII occurs at 5.5 hours.

Methylphenidate hydrochloride extended-release tablets once daily minimizes the fluctuations between peak and trough concentrations associated with immediate-release methylphenidate three times daily. Figure 1 displays mean plasma exposures of methylphenidate hydrochloride extended-release tablets once daily and methylphenidate three times daily (administered every 4 hours) in adults. Figure 1: Mean Methylphenidate Plasma Concentration-Time Profiles The mean single-dose pharmacokinetic parameters in 36 healthy adults following the administration of methylphenidate hydrochloride extended-release tablets 18 mg once daily and methylphenidate 5 mg three times daily are summarized in Table 7.

Table 7: Methylphenidate Pharmacokinetic Parameters (Mean ± SD) After Single Dose in Healthy Adults Parameters Methylphenidate Hydrochloride Extended-release Tablets (18 mg once daily) (n=36) Methylphenidate (5 mg three times daily) (n=35) C max (ng/mL) 3.7 ± 1.0 4.2 ±

1.0T max (h) 6.8 ± 1.8 6.5 ±

1.8AUC inf (ng∙h/mL) 41.8 ± 13.9 38.0 ± 11.0 t 1/2 (h) 3.5 ± 0.4 3.0 ±

0.5The pharmacokinetics of methylphenidate hydrochloride extended-release tablets were evaluated in healthy adults following single- and multiple-dose administration (steady state) of doses up to 144 mg per day (2 times the maximum recommended daily dosage of methylphenidate hydrochloride extended-release tablets). The mean half-life was about 3.6 hours. No differences in the pharmacokinetics of methylphenidate hydrochloride extended-release tablets were noted following single and repeated once-daily dosing, indicating no significant drug accumulation.

The AUC and t 1/2 following repeated once-daily dosing are similar to those following the first dose of methylphenidate hydrochloride extended-release tablets in a dose range of 18 mg to 144 mg. Effect of Food There were no differences in either the pharmacokinetics or the pharmacodynamic performance of methylphenidate hydrochloride extended-release tablets when administered after a high-fat breakfast. There is no evidence of dose dumping in the presence or absence of food.

Effect of Alcohol In-vitr o studies were conducted to explore the effect of alcohol on the release characteristics of methylphenidate from RELEXXII. At alcohol concentrations up to 40%, there was no increased release of methylphenidate in the first two hours. Dose Proportionality Following administration methylphenidate hydrochloride extended-release tablets in single doses of 18 mg, 36 mg, and 54 mg per day to healthy adults, C max and AUC (0–inf) of d-methylphenidate were proportional to dose, whereas l-methylphenidate C max and AUC (0–inf) increased disproportionately with respect to dose.

Following administration of methylphenidate hydrochloride extended-release tablets, plasma concentrations of the l-isomer were approximately 1/40 the plasma concentrations of the d-isomer. In healthy adults, single and multiple dosing of once-daily methylphenidate hydrochloride extended-release tablets doses from 54 mg to 144 mg per day resulted in linear and dose-proportional inc… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 48 words ▾

12.2Pharmacodynamics Methylphenidate is a racemic mixture comprised of the d- and l-threo entantiomers. The d-threo enantiomer is more pharmacologically active than the l-threo enantiomer. Methylphenidate blocks the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES The efficacy of RELEXXII for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients (6 to 17 years) and adult patients is based upon adequate and well-controlled studies of another formulation of methylphenidate hydrochloride extended-release tablets (referred to as “methylphenidate hydrochloride extended-release tablets” in the section below). The results of these adequate and well-controlled studies are presented below. Methylphenidate hydrochloride extended-release tablets was demonstrated to be effective in the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in four randomized, double-blind, placebo-controlled studies in pediatric patients 6 to 17 years and two double-blind placebo-controlled studies in adults who met the Diagnostic and Statistical Manual 4 th edition (DSM-IV) criteria for ADHD.

Pediatric Patients 6 to 12 Years Three double-blind, active- and placebo-controlled studies were conducted in 416 pediatric patients 6 to 12 years. The controlled studies compared methylphenidate hydrochloride extended-release tablets given once daily (18 mg, 36 mg, or 54 mg), methylphenidate given three times daily over 12 hours (15 mg, 30 mg, or 45 mg total daily dose), and placebo in two single-center, 3-week crossover studies (Studies 1 and 2) and in a multicenter, 4-week, parallel-group comparison (Study 3). The primary comparison of interest in all three trials was methylphenidate hydrochloride extended-release tablets versus placebo.

Symptoms of ADHD were evaluated by community schoolteachers using the Inattention/Overactivity with Aggression (IOWA) Conners scale. Statistically significant reduction in the Inattention/Overactivity subscale versus placebo was shown consistently across all three controlled studies for methylphenidate hydrochloride extended-release tablets. Studies 1 and 2 involved a 3-way crossover of 1 week per treatment arm.

Study 3 involved 4 weeks of parallel-group treatments with a Last Observation Carried Forward analysis at Week 4. The scores for methylphenidate hydrochloride extended-release tablets and placebo for the three studies are presented in Figure 2. Error bars represent the mean plus standard error of the mean.

Figure 2: Mean Community School Teacher IOWA Conners Inattention/Overactivity Scores with Methylphenidate Hydrochloride Extended-Release Tablets Once Daily (18 mg, 36 mg, or 54 mg) and Placebo (Studies 1, 2, and 3) In Studies 1 and 2, symptoms of ADHD were evaluated by laboratory schoolteachers using the Swanson, Kotkin, Agler, M-Fynn, and Pelham (SKAMP) laboratory school rating scale. The combined results from these two studies demonstrated statistically significant improvements in attention and behavior in patients treated with methylphenidate hydrochloride extended-release tablets versus placebo that were maintained through 12 hours after dosing.

Figure 3 presents the laboratory schoolteacher SKAMP ratings for methylphenidate hydrochloride extended-release tablets and placebo. Figure 3: Laboratory School Teacher SKAMP Ratings: Mean (SEM) of Combined Attention (Studies 1 and 2) Pediatric Patients 13 to 17 years In a randomized, double-blind, multicenter, placebo-controlled trial (Study 4) involving 177 patients, methylphenidate hydrochloride extended-release tablets was demonstrated to be effective in the treatment of ADHD in pediatric patients aged 13 to 18 years at doses up to 72 mg once daily (1.4 mg/kg/day).

Of 220 patients who entered an open 4-week titration phase, 177 were titrated to an individualized dose (maximum of 72 mg once daily) based on meeting specific improvement criteria on the ADHD Rating Scale and the Global Assessment of Effectiveness with acceptable tolerability. Patients who met these criteria were then randomized to receive either their individualized dose of methylphenidate hydrochloride extended-release tablets (18 mg to 72 mg once daily, n=87) or placebo (n=90) during a two-week double-blind… [Excerpted — this section continues on DailyMed.]

🔒 Drug Abuse and Dependence ~3 min read ▾

9 DRUG ABUSE AND DEPENDENCE

9.1Controlled Substance RELEXXII contains methylphenidate, a Schedule II controlled substance.

9.2Abuse RELEXXII has a high potential for abuse and misuse which can lead to the development of a substance use disorder, including addiction [see Warnings and Precautions ( 5.1 )] . RELEXXII can be diverted for non-medical use into illicit channels or distribution. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect.

Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.

Misuse and abuse of methylphenidate may cause increased heart rate, respiratory rate, or blood pressure; sweating; dilated pupils; hyperactivity; restlessness; insomnia; decreased appetite; loss of coordination; tremors; flushed skin; vomiting; and/or abdominal pain. Anxiety, psychosis, hostility, aggression, and suicidal or homicidal ideation have also been observed with CNS stimulants abuse and/or misuse. Misuse and abuse of CNS stimulants, including RELEXXII, can result in overdose and death [see Overdosage ( 10 )] , and this risk is increased with higher doses or unapproved methods of administration such as snorting or injection.

In two placebo-controlled human abuse potential studies, single oral doses of another formulation of methylphenidate hydrochloride extended-release tablets were compared to single oral doses of immediate-release methylphenidate (IR MPH) and placebo in subjects with a history of recreational stimulant use to assess relative abuse potential. For the purpose of this assessment, the response for each of the subjective measures was defined as the maximum effect within the first 8 hours after dose administration. In one study (n=40), both the other formulation of methylphenidate hydrochloride extended-release tablets (108 mg, which is 1.5 times the maximum recommended dosage of methylphenidate hydrochloride extended-release tablets) and 60 mg IR MPH compared to placebo produced statistically significantly greater responses on the five subjective measures suggestive of abuse potential.

In comparisons between the two active treatments, however, the other formulation of methylphenidate hydrochloride extended-release tablets (108 mg) produced variable responses on positive subjective measures that were either statistically indistinguishable from (Abuse Potential, Drug Liking, Amphetamine, and Morphine Benzedrine Group [Euphoria]) or statistically less than (Stimulation – Euphoria) responses produced by 60 mg IR MPH. In another study (n=49), both doses of another formulation of methylphenidate hydrochloride extended-release tablets (54 mg and 108 mg) and both doses of IR MPH (50 mg and 90 mg) produced statistically significantly greater responses compared to placebo on the two primary scales used in the study (Drug Liking, Euphoria).

When doses of the other methylphenidate hydrochloride extended-release tablets (54 mg and 108 mg) were compared to IR MPH (50 mg and 90 mg), respectively, methylphenidate hydrochloride extended-release tablets produced statistically significantly lower subjective responses on these two scales than IR MPH. Methylphenidate hydrochloride extended-release tablets (108 mg) produced responses that were statistically indistinguishable from the responses on these two scales produced by IR MPH (50 mg). Differences in subjective responses to the respective doses should be considered in the context that only 18% of the total amount of methylphenidate in RELEXXII i… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenesis In a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas and, in males only, an increase in hepatoblastomas at a daily dose of approximately 60 mg/kg/day. This dose is approximately 4 times the MRHD of methylphenidate hydrochloride extended-release tablets on a mg/m 2 basis, respectively. Hepatoblastoma is a relatively rare rodent malignant tumor type.

There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown. Methylphenidate did not cause any increases in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 6 times the MRHD of methylphenidate hydrochloride extended-release tablets on a mg/m 2 basis, respectively.

In a 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 to 74 mg/kg/day of methylphenidate. Mutagenesis Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or the in vitro mouse lymphoma cell forward mutation assay.

Sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay in cultured Chinese Hamster Ovary cells. Methylphenidate was negative in vivo in males and females in the mouse bone marrow micronucleus assay. Impairment of Fertility Methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week Continuous Breeding study.

The study was conducted at doses up to 160 mg/kg/day, approximately 11-fold the MRHD of methylphenidate hydrochloride extended-release tablets on a mg/m 2 basis, respectively.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~1 min read ▾

13.1Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenesis In a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas and, in males only, an increase in hepatoblastomas at a daily dose of approximately 60 mg/kg/day. This dose is approximately 4 times the MRHD of methylphenidate hydrochloride extended-release tablets on a mg/m 2 basis, respectively. Hepatoblastoma is a relatively rare rodent malignant tumor type.

There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown. Methylphenidate did not cause any increases in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 6 times the MRHD of methylphenidate hydrochloride extended-release tablets on a mg/m 2 basis, respectively.

In a 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 to 74 mg/kg/day of methylphenidate. Mutagenesis Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or the in vitro mouse lymphoma cell forward mutation assay.

Sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay in cultured Chinese Hamster Ovary cells. Methylphenidate was negative in vivo in males and females in the mouse bone marrow micronucleus assay. Impairment of Fertility Methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week Continuous Breeding study.

The study was conducted at doses up to 160 mg/kg/day, approximately 11-fold the MRHD of methylphenidate hydrochloride extended-release tablets on a mg/m 2 basis, respectively.

📄 Recent Major Changes 17 words ▾

RECENT MAJOR CHANGES Indications and Usage ( 1 ) 09/2025 Warnings and Precautions ( 5.7 ) 09/2025

📄 Package Label / Principal Display Panel 200 words ▾

PRINCIPAL DISPLAY PANEL RELEXXII ® 18 mg 100 count Bottle Label NDC 68025-095-10 RELEXXII 18 mg 100ct BL

PRINCIPAL DISPLAY PANEL RELEXXII ® 18 mg 30 count Bottle Label NDC 68025-095-30 RELEXXII 18 mg 30ct BL

PRINCIPAL DISPLAY PANEL RELEXXII ® 27 mg 100 count Bottle Label NDC 68025-096-10 RELEXXII 27 mg 100ct BL

PRINCIPAL DISPLAY PANEL RELEXXII ® 27 mg 30 count Bottle Label NDC 68025-096-30 RELEXXII 27 mg 30ct BL

PRINCIPAL DISPLAY PANEL RELEXXII ® 36 mg 100 count Bottle Label NDC 68025-097-10 RELEXXII 36 mg 100ct BL

PRINCIPLE DISPLAY PANEL RELEXXII ® 36 mg 30 count Bottle Label NDC 68025-097-30 RELEXXII 36 mg 30ct BL

PRINCIPAL DISPLAY PANEL RELEXXII ® 45 mg 30 count Bottle Label NDC 68025-088-30 RELEXXII 45 mg 30ct Bottle Label

PRINCIPAL DISPLAY PANEL RELEXXII ® 54 mg 100 count Bottle Label NDC 68025-098-10 RELEXXII 54 mg 100ct BL

PRINCIPLE DISPLAY PANEL RELEXXII ® 54 mg 30 count Bottle Label NDC 68025-098-30 RELEXXII 54 mg 30ct BL

PRINCIPAL DISPLAY PANEL RELEXXII ® 63 mg 30 count Bottle Label NDC 68025-089-30 RELEXXII 63 mg 30ct Bottle Label

PRINCIPAL DISPLAY PANEL RELEXXII ® 72 mg 30 count Bottle Label NDC 68025-084-30 RELEXXII 72 mg 30ct BL

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

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 this package alone, 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 – Q4 2025 · 4 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
77
Units reimbursed last 4 qtrs
2.4K
Gross reimbursed last 4 qtrs
$52.9K
Avg / prescription
$686.74
Avg / unit
$22.3118
Latest quarter Q4 2025
50Rx
Medicaid pays / ea
$22.3118
gross reimbursed
vs
NADAC / ea
$22.0992
acquisition cost
=
Spread
+$0.2126
+1% 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% MCO
Fee-for-service · 0 Rx Managed care · 77 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: no data reported MI New York: no data reported 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: 450 units · 6.6 per 100k residents IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: no data reported 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: 900 units · 8.3 per 100k residents 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: 1,020 units · 3.3 per 100k residents TX Florida: no data reported FL
Units reimbursed · per 100k residents
3.38.3
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 North Carolina 8.3 /100k
2 Indiana 6.6 /100k
3 Texas 3.3 /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 tablets this page68025-0084-30 77 Rx · $52,879
100 tablets68025-0084-10 No Medicaid data
Drug total (last 4 qtrs): 77 Rx · 2,370 units · $52,879 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 Relexxii — 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 Relexxii. 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
$19.7K
Claims incl. refills
33
Beneficiaries
19
Spend / beneficiary
$1,034.94
Spend / claim
$595.87
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 RELEXXII (this brand).

Top reported reactions

Headache396
Fatigue353
Anxiety347
Nausea329
Toxicity To Various Agents326
Drug Abuse279
Somnolence269

Reporter sex

6,780 reports
Male · 52%
Female · 46%
Unknown · 1%

Serious outcomes

Hospitalization1,651
Death434
Disabling146
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 728 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.
← 68025-0083-07 · Vertical 68025-0086-07 · Vertical →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.