NDC 72912-570 Adhansia Xr

Methylphenidate Hydrochloride Extented Release Capsules

NDC Product Code 72912-570

NDC Code: 72912-570

Proprietary Name: Adhansia Xr Additional informationCallout TooltipWhat is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Methylphenidate Hydrochloride Extented Release Capsules Additional informationCallout TooltipWhat is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.


Product Characteristics
Color(s):
BLUE (C48333)
ORANGE (C48331)
YELLOW (C48330)
GREEN (C48329)
GRAY (C48324)
Shape: CAPSULE (C48336)
Size(s):
18 MM
19 MM
22 MM
24 MM
Imprint(s):
MLR02;25MG
MLR02;35MG
MLR02;45MG
MLR02;55MG
MLR02;70MG
Score: 1

Code Structure
  • 72912 - Adlon Therapeutics L.p.
    • 72912-570 - Adhansia Xr

NDC 72912-570-10

Package Description: 100 CAPSULE, EXTENDED RELEASE in 1 BOTTLE

NDC Product Information

Adhansia Xr with NDC 72912-570 is a a human prescription drug product labeled by Adlon Therapeutics L.p.. The generic name of Adhansia Xr is methylphenidate hydrochloride extented release capsules. The product's dosage form is capsule, extended release and is administered via oral form.

Labeler Name: Adlon Therapeutics L.p.

Dosage Form: Capsule, Extended Release - A solid dosage form in which the drug is enclosed within either a hard or soft soluble container made from a suitable form of gelatin, and which releases a drug (or drugs) in such a manner to allow a reduction in dosing frequency as compared to that drug (or drugs) presented as a conventional dosage form.

Product Type: Human Prescription Drug Additional informationCallout TooltipWhat kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

DEA Schedule: Schedule II (CII) Substances Additional informationCallout TooltipWhat is the Drug Enforcement Administration (DEA) CII Schedule?
The controlled substances in the CII schedule have a high abuse potential with severe psychological or physical dependence liability, but have accepted medical use in the United States. Schedule CII controlled substances include certain narcotic, stimulant, and depressant drugs.


Adhansia Xr Active Ingredient(s)

Additional informationCallout TooltipWhat is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • METHYLPHENIDATE HYDROCHLORIDE 70 mg/1

Inactive Ingredient(s)

Additional informationCallout TooltipAbout the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • AMMONIO METHACRYLATE COPOLYMER TYPE B (UNII: 161H3B14U2)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • GLYCERYL MONOSTEARATE (UNII: 230OU9XXE4)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • POLYSORBATE 20 (UNII: 7T1F30V5YH)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • SORBIC ACID (UNII: X045WJ989B)
  • SUCROSE (UNII: C151H8M554)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • AMMONIO METHACRYLATE COPOLYMER TYPE B (UNII: 161H3B14U2)
  • GLYCERYL MONOSTEARATE (UNII: 230OU9XXE4)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • POLYSORBATE 20 (UNII: 7T1F30V5YH)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • SORBIC ACID (UNII: X045WJ989B)
  • SUCROSE (UNII: C151H8M554)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
  • AMMONIO METHACRYLATE COPOLYMER TYPE B (UNII: 161H3B14U2)
  • GLYCERYL MONOSTEARATE (UNII: 230OU9XXE4)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • POLYSORBATE 20 (UNII: 7T1F30V5YH)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • SORBIC ACID (UNII: X045WJ989B)
  • SUCROSE (UNII: C151H8M554)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • FD&C YELLOW NO. 5 (UNII: I753WB2F1M)
  • AMMONIO METHACRYLATE COPOLYMER TYPE B (UNII: 161H3B14U2)
  • GLYCERYL MONOSTEARATE (UNII: 230OU9XXE4)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • POLYSORBATE 20 (UNII: 7T1F30V5YH)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • SORBIC ACID (UNII: X045WJ989B)
  • SUCROSE (UNII: C151H8M554)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • FERRIC OXIDE YELLOW (UNII: EX438O2MRT)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • AMMONIO METHACRYLATE COPOLYMER TYPE B (UNII: 161H3B14U2)
  • GLYCERYL MONOSTEARATE (UNII: 230OU9XXE4)
  • HYPROMELLOSE, UNSPECIFIED (UNII: 3NXW29V3WO)
  • POLYETHYLENE GLYCOL, UNSPECIFIED (UNII: 3WJQ0SDW1A)
  • POLYSORBATE 20 (UNII: 7T1F30V5YH)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • SODIUM HYDROXIDE (UNII: 55X04QC32I)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • SORBIC ACID (UNII: X045WJ989B)
  • SUCROSE (UNII: C151H8M554)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • TRIETHYL CITRATE (UNII: 8Z96QXD6UM)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)

Administration Route(s)

Additional informationCallout TooltipWhat are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

Additional informationCallout TooltipWhat is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Central Nervous System Stimulant - [EPC] (Established Pharmacologic Class)
  • Central Nervous System Stimulation - [PE] (Physiologic Effect)

Product Labeler Information

Additional informationCallout TooltipWhat is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Adlon Therapeutics L.p.
Labeler Code: 72912
FDA Application Number: NDA212038 Additional informationCallout TooltipWhat is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: NDA - A product marketed under an approved New Drug Application. Additional informationCallout TooltipWhat is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 03-11-2019 Additional informationCallout TooltipWhat is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 Additional informationCallout TooltipWhat is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N Additional informationCallout TooltipWhat is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Adhansia Xr Product Label Images

Adhansia Xr Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Warning: Abuse And Dependence

CNS stimulants, including ADHANSIA XR, other methylphenidate-containing
products, and amphetamines, have a high potential for abuse and dependence.
Assess the risk of abuse prior to prescribing, and monitor for signs
of abuse and dependence while on therapy [see Warnings and
Precautions (5.1), Drug Abuse and
Dependence (9.2, 9.3)].

1 Indications And Usage

ADHANSIA XRTM is a central nervous system (CNS) stimulant indicated
for the treatment of Attention Deficit Hyperactivity Disorder (ADHD)
in patients 6 years and older [see Clinical Studies (14)].

2.1 Pretreatment Screening

Prior to initiating
treatment with ADHANSIA XR, 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)].Assess the risk of abuse prior
to prescribing and monitor for signs of abuse and dependence while
on therapy. Maintain careful prescription records, educate patients
about abuse, and periodically re-evaluate the need for ADHANSIA XR
use [see Boxed Warning, Warnings and Precautions (5.1), and Drug Abuse and
Dependence (9)].

2.2 General Dosing Information

Administer ADHANSIA XR orally once daily
in the morning with or without food. The recommended starting dose of ADHANSIA
XR for patients 6 years or older is 25 mg once daily. Titrate the
dose in increments of 10 to 15 mg at intervals of no less than 5 days.
Dosages higher than 100 mg daily in adults and 85 mg daily in pediatric
patients have not been evaluated in clinical trials and are not recommended.
Although efficacy was demonstrated in short-term controlled trials
in adults at dosages of 100 mg daily, dosages above 85 mg daily were
associated with a disproportionate increase in the incidence of certain
adverse reactions. In short-term controlled trials in pediatric patients,
efficacy was demonstrated at dosages of 70 mg daily, but dosages 70
mg daily and higher were associated with a disproportionate increase
in the incidence of certain adverse reactions [see Adverse
Reactions (6.1), Clinical Studies
(14)]. Individualize dosage
adjustments based upon assessment of clinical benefit and tolerability
with careful consideration of the dose-related adverse reactions.ADHANSIA XR may be taken whole
or the capsule may be opened and the entire contents sprinkled onto
a tablespoon of applesauce or yogurt. The entire mixture should be
consumed immediately or within 10 minutes. If the mixture is not
consumed within 10 minutes after mixing, it should be discarded and
not stored. Patients should take the entire contents of the capsule
sprinkled on the chosen food in its entirety, without chewing. The
dose of a single capsule should not be divided. Patients should not
take anything less than one capsule per day.In the event of a missed dose, do not administer
later in the day. Do not administer additional medication to make
up for the missed dose [see Adverse Reactions (6.1), Clinical Studies (14)].Pharmacological treatment of ADHD may be
needed for extended periods. Periodically re-evaluate the long-term
use of ADHANSIA XR, and adjust dosage as needed.

2.3 Dose Reduction And Discontinuation

If paradoxical aggravation of symptoms or
other adverse reactions occur, reduce the dosage, or, if necessary,
discontinue the drug. ADHANSIA XR should be periodically discontinued
to assess the patient's condition. If improvement is not observed
after appropriate dosage adjustment over a one-month period, discontinue
ADHANSIA XR.

2.4 Switching From Other Methylphenidate Products

If switching from other methylphenidate products,
discontinue that treatment, and titrate with ADHANSIA XR using the
titration schedule above.Do not substitute ADHANSIA XR for other methylphenidate products
on a milligram-per-milligram basis because of different methylphenidate
base compositions and differing pharmacokinetic profiles [see
Description (11) and Clinical Pharmacology
(12.3)].

3 Dosage Forms And Strengths

  • 25 mg (methylphenidate hydrochloride) Extended-Release
  • Capsules – blue capsule(imprinted with
  • “MLR-02” on cap and “25 mg” on the body)Contains
  • 25 mg methylphenidate hydrochloride, equivalent to 21.6 mg of methylphenidate 35 mg (methylphenidate hydrochloride) Extended-Release
  • Capsules – orange capsule(imprinted with
  • “MLR-02” on cap and “35 mg” on the body)Contains
  • 35 mg methylphenidate hydrochloride, equivalent to 30.3 mg of methylphenidate45 mg (methylphenidate hydrochloride) Extended-Release
  • Capsules – yellow capsule(imprinted with
  • “MLR-02” on cap and “45 mg” on the body)Contains
  • 45 mg methylphenidate hydrochloride, equivalent to 38.9 mg of methylphenidate55 mg (methylphenidate hydrochloride) Extended-Release
  • Capsules – light green capsule(imprinted
  • With “MLR-02” on cap and “55 mg” on the body)Contains 55 mg methylphenidate hydrochloride, equivalent to 47.6
  • Mg of methylphenidate 70 mg (methylphenidate hydrochloride) Extended-Release
  • Capsules – iron gray capsule(imprinted
  • With “MLR-02” on cap and “70 mg” on the body)Contains 70 mg methylphenidate hydrochloride, equivalent to 60.5
  • Mg of methylphenidate85 mg (methylphenidate hydrochloride) Extended-Release
  • Capsules – white capsule(imprinted with
  • “MLR-02” on cap and “85 mg” on the body)Contains
  • 85 mg methylphenidate hydrochloride, equivalent to 73.5 mg of methylphenidate

4 Contraindications

  • ADHANSIA XR is contraindicated in patients:With a known hypersensitivity to methylphenidate or other
  • Components of ADHANSIA XR. 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)].

5.1 Potential For Abuse And Dependence

CNS stimulants, including ADHANSIA XR, other
methylphenidate-containing products, and amphetamines, have a high
potential for abuse and dependence. Assess the risk of abuse prior
to prescribing, and monitor for signs of abuse and dependence while
on therapy [see Drug Abuse and Dependence (9.2, 9.3)].

5.2 Serious Cardiovascular Events

Sudden death, stroke and myocardial infarction
have occurred in adults treated with CNS stimulant treatment at recommended
doses. Sudden death has occurred in pediatric patients with structural
cardiac abnormalities and other serious cardiac problems taking CNS
stimulants at recommended doses for ADHD. Avoid use in patients with
known structural cardiac abnormalities, cardiomyopathy, serious heart
arrhythmia, coronary artery disease, and other serious heart problems.
Further evaluate patients who develop exertional chest pain, unexplained
syncope, or arrhythmias during treatment during ADHANSIA XR treatment.

5.3 Blood Pressure And Heart Rate Increases

CNS stimulants cause an increase in blood
pressure (mean increase approximately 2 to 4 mmHg) and heart rate
(mean increase approximately 3 to 6 bpm). Individuals may have larger
increases. Monitor all patients for hypertension and tachycardia.

5.4 Psychiatric Adverse Reactions

Exacerbation of Pre-Existing PsychosisCNS stimulants may exacerbate symptoms of behavior disturbance
and thought disorder in patients with a pre-existing psychotic disorder.Induction of a Manic
Episode in Patients with Bipolar DisorderCNS
stimulants may induce a manic or mixed episode in patients. Prior
to initiating treatment, screen patients for risk factors for developing
a manic episode (e.g., comorbid or history of depressive symptoms
or a family history of suicide, bipolar disorder, or depression).New Psychotic or Manic
SymptomsCNS stimulants, at recommended doses,
may cause psychotic or manic symptoms (e.g., hallucinations, delusional
thinking, or mania) in patients without a prior history of psychotic
illness or mania. If such symptoms occur, consider discontinuing ADHANSIA
XR. In a pooled analysis of multiple short-term, placebo-controlled
studies of CNS stimulants, psychotic or manic symptoms occurred in
approximately 0.1% of CNS stimulant-treated patients, compared to
0% in placebo-treated patients.

5.5 Priapism

Prolonged and painful erections,
sometimes requiring surgical intervention, have been reported with
methylphenidate products, in both pediatric and adult patients. Priapism
was not reported with drug initiation but developed after some time
on the drug, often subsequent to an increase in dose. Priapism has
also appeared during a period of drug withdrawal (drug holidays or
during discontinuation). Patients who develop abnormally sustained
or frequent and painful erections should seek immediate medical attention.

5.6 Peripheral Vasculopathy, Including Raynaud’S Phenomenon

CNS stimulants, including ADHANSIA XR, used
to treat ADHD are associated with peripheral vasculopathy, including
Raynaud’s phenomenon. Signs and symptoms are usually intermittent
and mild; however, very rare sequelae include digital ulceration and/or
soft tissue breakdown. Effects of peripheral vasculopathy, including
Raynaud’s phenomenon, were observed in post-marketing reports at different
times and at therapeutic doses in all age groups throughout the course
of treatment. Signs and symptoms generally improve after reduction
in dose or discontinuation of drug. Careful observation for digital
changes is necessary during treatment with ADHD stimulants. Further
clinical evaluation (e.g., rheumatology referral) may be appropriate
for certain patients.

5.7 Long-Term Suppression Of Growth

CNS stimulants have been associated with
weight loss and slowing of growth rate in pediatric patients.Careful follow-up of weight and
height in pediatric patients ages 7 to 10 years who were randomized
to either methylphenidate or non-medication treatment groups over
14 months, as well as in naturalistic subgroups of newly methylphenidate-treated
and non-medication treated pediatric patients over 36 months (to the
ages of 10 to 13 years), suggests that consistently medicated pediatric
patients (i.e., treatment for 7 days per week throughout the year)
have a temporary slowing in growth rate (on average, a total of about
2 cm less growth in height and 2.7 kg less growth in weight over 3
years), without evidence of growth rebound during this period of development.Closely monitor growth (weight
and height) in pediatric patients treated with CNS stimulants, including
ADHANSIA XR. Patients who are not growing or gaining height or weight
as expected may need to have their treatment interrupted.

5.8 Allergic-Type Reactions: Fd&C Yellow No. 5

ADHANSIA XR 45 mg capsules contain FD&C
Yellow No. 5 (tartrazine) which may cause allergic-type reactions
(including bronchial asthma) in certain susceptible persons. Although
the overall incidence of FD&C Yellow No. 5 (tartrazine) sensitivity
in the general population is low, it is frequently seen in patients
who also have aspirin hypersensitivity [see Contraindications
(4)].

6 Adverse Reactions

  • The following are discussed in more detail in other sections
  • Of the labeling:Known hypersensitivity to methylphenidate or other ingredients
  • Of ADHANSIA XR [see Contraindications (4)]Hypertensive crisis when used concomitantly with monoamine
  • Oxidase inhibitors [see Contraindications (4) and Drug Interactions (7.1)]Drug dependence [see Boxed Warning, Warnings and
  • Precautions (5.1), and Drug Abuse
  • And Dependence (9.2, 9.3)]Serious cardiovascular reactions [see Warnings and
  • Precautions (5.2)]Blood pressure and heart rate increases [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 [see Warnings and
  • Precautions (5.7)]Allergic Reactions FD&C Yellow No.5 [see Warnings
  • And Precautions (5.8)]

6.1 Clinical Trial Experience

Because clinical trials are conducted under
widely varying conditions, adverse reaction rates observed in the
clinical trials of a drug cannot be directly compared to rates in
the clinical trials of another drug and may not reflect the rates
observed in clinical practice.Clinical Trials Experience with
Other Methylphenidate Products in Children, Adolescents, and Adults
with ADHDCommonly reported (≥2% of the methylphenidate
group and twice the rate of the placebo group) adverse reactions from
placebo-controlled trials of methylphenidate products include: appetite
decreased, weight decreased, nausea, abdominal pain, dyspepsia, dry
mouth, vomiting, insomnia, anxiety, nervousness, restlessness, affect
lability, agitation, irritability, dizziness, vertigo, tremor, blurred
vision, blood pressure increased, heart rate increased, tachycardia,
palpitations, hyperhidrosis, and pyrexia.Clinical Trials Experience with
ADHANSIA XRADHANSIA XR was studied in adults
(18 to 72 years) and pediatric patients (6 to 17 years) who met Diagnostic
and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for ADHD.The safety data for adults is based on two
randomized, double-blind, placebo-controlled studies in doses of 25
mg to 100 mg per day. The safety data for pediatric patients (6 to
17 years) is based on randomized, double-blind, placebo-controlled
studies in doses of 25 mg to 85 mg per day.The total number of patients exposed to ADHANSIA
XR during 1 to 4-week long, controlled treatment periods is 883; this
included 434 adult patients and 449 pediatric patients [156 (6 to
12 years); 293 (12 to 17 years)], from two clinical trials in adults,
one in pediatric patients ages 12 to 17 years, and one in pediatric
patients ages 6 to 12 years [see Clinical Studies (14)].Adverse Reactions Leading to Discontinuation
of TreatmentIn controlled adult trials for
Study 1, 3% of both of ADHANSIA XR-treated patients and placebo-treated
patients discontinued due to adverse reactions. In an adult workplace
environment study (Study 2), 10% of ADHANSIA XR-treated patients discontinued
due to adverse reactions compared to 0% of placebo-treated patients.
The following adverse reactions led to discontinuation at a frequency
of 2% of ADHANSIA XR-treated patients: nausea, bronchitis, gastroenteritis
viral, viral infection, blood pressure increased, and hypomania.In a controlled trial (Study
3) in pediatric patients (12 to 17 years), 3% of ADHANSIA XR-treated
patients discontinued due to adverse reactions compared to 0% of placebo-treated
patients. The most frequent adverse reactions leading to discontinuation
in at least 1% of ADHANSIA XR-treated patients and at a rate greater
that placebo was irritability (1%). Two patients taking ADHANSIA XR
70 or 85 mg had delirium leading to discontinuation.In a controlled trial (Study 4) in pediatric
patients (6 to 12 years), 1% of of ADHANSIA XR-treated patients discontinued
due to adverse reactions compared to 0% of placebo-treated patients.Adult Patients with
ADHDThe most common adverse reactions (incidence
of ≥5% and at least twice placebo) of ADHANSIA XR occurring in controlled
trials in adults were insomnia, dry mouth, and decreased appetite.Table 1 lists the adverse reactions
that occurred ≥2% of adult patients and greater than placebo among
ADHANSIA XR-treated adult patients.Table 1: Adverse Reactions Occurring in ≥ 2% of Adult Patients
with ADHD on ADHANSIA XR and Greater than Patients Taking Placebo
in a 4-week Clinical TrialAdverse ReactionADHANSIA XRAll dosesADHANSIA XRPlacebo 25 mg45 mg70 mg100 mg  N=375(N=77)(N=73)(N=73)(N=100)(N=297)(N=78)Initial Insomnia4%8%6%7%5%1%Insomnia17%11%16%19%13%4%Dry mouth8%8%7%14%8%4%Nausea4%6%4%11%5%3%Diarrhea1%3%7%5%3%1%Decreased appetite4%7%15%19%9%3%Feeling jittery1%3%8%4%4%1%Weight decreased3%4%3%5%3%1%Upper respiratory
tract infection0%4%3%3%2%1%Pediatric
Patients (12 to 17 years) with ADHDThe most
common (incidence ≥5% and at least twice placebo) adverse reactions
reported in pediatric patients (12 to 17 years) were decreased appetite,
insomnia, and weight decreased. Table 2 lists the adverse reactions that
occurred ≥2% of pediatric patients (12 to 17 years) and greater than
placebo among ADHANSIA XR-treated pediatric patients (12 to 17 years).Table 2: Adverse Reactions Occurring in ≥ 2% of Pediatric
Patients (12 to 17 years) with ADHD Taking ADHANSIA XR and Greater
than Placebo in a 4-week Clinical TrialAdverse ReactionADHANSIA XRAll dosesADHANSIA XRPlacebo 25 mg45 mg70 mg85 mg   (N=73)(N=72)(N=76)(N=72)(N=293)(N=74)Decreased appetite7%19%28%26%20%0%Insomnia4%0%9%13%6%1%Initial Insomnia4%7%5%4%5%1%Weight decreased1%3%8%13%7%0%Abdominal pain
upper5%1%5%4%4%1%Nausea3%6%7%8%6%4%Dizziness3%0%4%4%3%0%Dry mouth1%0%5%4%3%1%Vomiting1%1%3%6%3%0%Pediatric
Patients (6 to 12 years) with ADHDStudy 4,
conducted in pediatric patients 6 to 12 years of age, was comprised
of a 6-week open-label dose-optimization phase in which all patients
received ADHANSIA XR (n=156; mean dose 48 mg), followed by a 1-week,
double-blind controlled phase in which patients were randomized to
continue ADHANSIA XR (n=75) or switch to placebo (n=73). During the
open-label ADHANSIA XR treatment phase, adverse reactions reported
in > 5% of patients included: decreased appetite (35%), upper abdominal
pain (15%), affect lability (13%), nausea or vomiting (13%), weight
decreased (12%), insomnia (10%), irritability (10%), headache (10%),
and heart rate increased (5%). Because of the trial design (6-week
open-label active treatment phase followed by a 1-week, randomized,
double-blind, placebo-controlled withdrawal), the adverse reaction
rates described in the double-blind phase are lower than expected
in clinical practice. No difference occurred in the incidence of adverse
reactions between ADHANSIA XR and placebo during the 1-week, double-blind,
placebo-controlled treatment phase.

6.2 Post-Marketing Experience

The following adverse reactions have been identified during post
approval use of methylphenidate products. Because these reactions
are reported voluntarily from a population of uncertain size, it is
not possible to reliably estimate their frequency or establish a causal
relationship to drug exposure. These adverse reactions are as follows:Blood and Lymphatic
System Disorders: pancytopenia, thrombocytopenia, thrombocytopenic
purpuraCardiac
Disorders: angina pectoris, bradycardia, extrasystole, supraventricular
tachycardia, ventricular extrasystoleEye Disorders: diplopia,
mydriasis, visual impairmentGeneral Disorders: chest
pain, chest discomfort, hyperpyrexiaHepatobiliary disorders: hepatocellular injury, acute hepatic failureImmune System Disorders: hypersensitivity reactions such as angioedema, anaphylactic reactions,
auricular swelling, bullous conditions, exfoliative conditions, urticarias,
pruritus, rashes, eruptions, and exanthemas Investigations: alkaline
phosphatase increased, bilirubin increased, hepatic enzyme increased,
platelet count decreased, white blood cell count abnormal Musculoskeletal, Connective
Tissue and Bone Disorders: arthralgia, myalgia, muscle twitching,
rhabdomyolysisNervous System Disorders: convulsion, grand mal convulsion,
dyskinesia, serotonin syndrome in combination with serotonergic drugsPsychiatric Disorders: disorientation, hallucination, hallucination auditory, hallucination
visual, libido changes, logorrhea, mania Skin and Subcutaneous Tissue Disorders: alopecia, erythemaUrogenital System: priapismVascular Disorders: Raynaud’s
phenomenon

7.1 Clinically Important Drug Interactions

Table 3 presents clinically important drug
interactions with ADHANSIA XR.Table 3: Drugs Having Clinically Important Interactions with
ADHANSIA XRMonoamine
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 ADHANSIA XR
concomitantly with MAOIs or within 14 days after discontinuing MAOI
treatment.Examples:selegiline, tranylcypromine,
isocarboxazid, phenelzine, linezolid, methylene blueGastric pH
ModulatorsClinical Impact:May change the release, PK profiles
and alter the pharmacodynamics of ADHANSIA XR.Intervention:Monitor patients for changes
in clinical effect and use alternative therapy based on clinical response.Examples:Omeprazole, esomeprazole, pantoprazole,
famotidine, sodium bicarbonate

8.1 Pregnancy

Pregnancy Exposure RegistryThere
is a pregnancy exposure registry that monitors pregnancy outcomes
in women exposed to ADHANSIA XR during pregnancy. Healthcare providers
are encouraged to register patients by calling the National Pregnancy
Registry for Psychostimulants at 1-866-961-2388.Risk SummaryPublished studies and post-marketing reports on methylphenidate
use during pregnancy are insufficient to identify a drug-associated
risk of major birth defects, miscarriage or adverse maternal of 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 embryo-fetal
studies with oral administration of methylphenidate to pregnant rats
and rabbits during organogenesis at doses up to 7 and 11 times, respectively,
the maximum recommended human dose (MRHD) of 85 mg/day given to adolescents
on a mg/m2 basis. However, fetal spina
bifida was observed in rabbits at a dose 36 times the MRHD given to
adolescents. A decrease in pup body weight was observed in a pre-
and post-natal development study with oral administration of methylphenidate
to rats throughout pregnancy and lactation at doses 4 times the MRHD
given to adolescents [see Data].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 ConsiderationsFetal/Neonatal Adverse ReactionsCNS stimulants, such as ADHANSIA XR, 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.DataAnimal DataIn embryo-fetal development studies conducted in rats and rabbits,
methylphenidate was administered orally at doses of up to 75 and 200
mg/kg/day, respectively, during the period of organogenesis. Malformations
(increased incidence of fetal spina bifida) were observed in rabbits
at the highest dose. which is approximately 36 times the maximum recommended
human dose (MRHD) of 85 mg/day given to adolescents on a mg/m2 basis. The no effect level for embryo-fetal development
in rabbits was 60 mg/kg/day (11 times the MRHD given to adolescents
on a mg/m2 basis). There was no evidence
of morphological development effects in rats, although increased incidences
of fetal skeletal variations were seen at the highest dose level (7
times the MRHD given to adolescents on a mg/m2 basis), which was also maternally toxic. The no effect level for
embryo-fetal development in rats was 25 mg/kg/day. (2 times the MRHD
given to adolescents on a mg/m2 basis). When methylphenidate was administered
to rats throughout pregnancy and lactation at doses of up to 45 mg/kg/day,
offspring body weight gain was decreased at the highest dose (4 times
the MRHD on a mg/m2 basis), but no other
effects on postnatal development were observed. The no effect level
for pre- and postnatal development in rats was 15 mg/kg/day (equivalent
to the MRHD given to adolescents on a mg/m2 basis).

8.2 Lactation

Risk SummaryLimited 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. Long-term neurodevelopmental
effects on infants from stimulant exposure are unknown. The developmental
and health benefits of breastfeeding should be considered along with
the mother’s clinical need for ADHANSIA XR and any potential adverse
effects on the breastfed infant from ADHANSIA XR or from the underlying
maternal condition.Clinical ConsiderationsMonitor
breastfeeding infants for adverse reactions, such as agitation, anorexia,
and reduced weight gain.

8.4 Pediatric Use

Safety and effectiveness of ADHANSIA XR in pediatric patients
under the age of 6 years have not been established.The safety and effectiveness of ADHANSIA
XR have been established in one adequate and well-controlled 6-week
study in pediatric patients ages 6 to 12 years, and in one adequate
and well-controlled 4-week study in pediatric patients ages 12 to
17 years [see Clinical Studies (14)]. The long-term efficacy of methylphenidate in pediatric
patients has not been established.Long Term Suppression of GrowthGrowth should be monitored during treatment with stimulants,
including ADHANSIA XR. Pediatric patients who are not growing or
gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions (5.7)].Juvenile Animal Toxicity DataRats treated
with methylphenidate early in the postnatal period through sexual
maturation demonstrated a decrease in spontaneous locomotor activity
in adulthood. A deficit in acquisition of a specific learning task
was observed in females only. The doses at which these findings were
observed are at least 3 times the maximum recommended human dose (MRHD)
of 85 mg/day given to children on a mg/m2 basis.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 3
times the MRHD of 85 mg/day given to children on a mg/m2 basis) or greater, and a deficit in the acquisition
of a specific learning task was observed in females exposed to the
highest dose (6 times the MRHD given to children on a mg/m2 basis). The no effect level for juvenile neurobehavioral
development in rats was 5 mg/kg/day (approximately 0.25 times the
MRHD given to children on a mg/m2 basis).
The clinical significance of the long-term behavioral effects observed
in rats is unknown.

8.5 Geriatric Use

ADHANSIA XR has not been studied in the patients over the
age of 72 years.

9.1 Controlled Substance

ADHANSIA XR contains methylphenidate, a Schedule II controlled
substance.

9.2 Abuse

CNS stimulants including ADHANSIA XR, other methylphenidate-containing
products, and amphetamines have a high potential for abuse. Abuse
is the intentional non-therapeutic use of a drug, even once, to achieve
a desired psychological or physiological effect. Abuse is characterized
by impaired control over drug use, compulsive use, continued use despite
harm, and craving.Signs and symptoms of CNS stimulant abuse include increased heart
rate, respiratory rate, blood pressure, and/or sweating, dilated pupils,
hyperactivity, restlessness, insomnia, decreased appetite, loss of
coordination, tremors, flushed skin, vomiting, and/or abdominal pain.
Anxiety, psychosis, hostility, aggression, suicidal or homicidal
ideation have also been observed. Abusers of CNS stimulants may chew,
snort, inject, or use other unapproved routes of administration which
can result in overdose and death [see Overdosage (10)].To reduce the abuse of CNS stimulants including
ADHANSIA XR, assess the risk of abuse prior to prescribing. After
prescribing, keep careful prescription records, educate patients and
their families about abuse and on proper storage and disposal of CNS
stimulants, monitor for signs of abuse while on therapy, and re-evaluate
the need for ADHANSIA XR use.

9.3 Dependence

ToleranceTolerance (a state of
adaptation in which exposure to a drug results in a reduction of the
drug’s desired and/or undesired effects over time) may occur during
chronic therapy with CNS stimulants including ADHANSIA XR.DependencePhysical dependence (a state of adaptation manifested
by a withdrawal syndrome produced by abrupt cessation, rapid dose
reduction, or administration of an antagonist) can occur in patients
treated with CNS stimulants including ADHANSIA XR. Withdrawal symptoms
after abrupt cessation following prolonged high-dosage administration
of CNS stimulants include dysphoric mood; depression; fatigue; vivid,
unpleasant dreams; insomnia or hypersomnia; increased appetite; and
psychomotor retardation or agitation.

10.1 Signs And Symptoms

Signs and symptoms of acute methylphenidate overdosage, resulting
principally from overstimulation of the CNS and from excessive sympathomimetic
effects, may include the following: nausea, vomiting, diarrhea, restlessness,
anxiety, agitation, tremors, hyperflexia, muscle twitching, convulsion
(may be followed by coma), euphoria, confusion, hallucinations, delirium,
sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations,
cardiac arrhythmias, hypertension, hypotension, tachypnea, mydriasis,
dryness of mucous membranes, and rhabdomyolysis.

10.2 Management Of Overdose

Consult with a Certified Poison Control Center (1-800-222-1222) for
up-to-date guidance and advice on the management of overdosage with
methylphenidate. Provide supportive care, including close medical
supervision and monitoring. Treatment should consist of general measures
employed in the management of overdosage with any drug. Consider
the possibility of multiple drug overdosage. Ensure an adequate airway,
oxygenation, and ventilation. Monitor cardiac rhythm and vital signs.
Use supportive and symptomatic measures.

11 Description

  • ADHANSIA XR extended release capsules contains
  • Methylphenidate hydrochloride, a CNS stimulant. The capsules contain
  • Multilayered beads, composed of an immediate-release (IR) layer which
  • Contains approximately 20% of the methylphenidate dose, and a controlled
  • Release layer which contains approximately 80% of the methylphenidate
  • Dose, for oral administration. ADHANSIA XR is available in six capsule
  • Strengths. Each extended-release capsule contains 25 mg, 35 mg, 45
  • Mg, 55 mg, 70 mg, or 85 mg of methylphenidate hydrochloride (HCl),
  • Which is equivalent to 21.6 mg, 30.3 mg, 38.9, mg, 47.6 mg, 60.5 mg,
  • And 73.5 mg of methylphenidate free base, respectively. Chemically,
  • Methylphenidate HCl is d,l(racemic) methyl α-phenyl-2-piperidineacetate
  • Hydrochloride. Its molecular formula is C14H19NO2●HCl. Its structural
  • Formula is:Methylphenidate HCl is a white to off-white,
  • Odorless, fine 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. Its molecular weight
  • Is 269.8 g/mol.Inactive Ingredients: ammonio methacrylate
  • Copolymer dispersion (type B), anionic copolymer (consisting of methyl
  • Acrylate, methyl methacrylate and methacrylic acid), glyceryl monostearate,
  • Hypromellose, poylethylene glycol, polysorbate, silicon dioxide, sodium
  • Hydroxide, sodium laurylsulfate, sorbic acid, sugar spheres, triethyl
  • Citrate.Each strength
  • Capsule also contains colorant ingredients in the capsule shell as
  • Follows:25 mgFD&C Blue No. 135 mgFD&C Yellow No. 6, Titanium Dioxide45 mgFD&C Yellow No. 5, Titanium Dioxide55 mgFD&C Blue No. 1, Yellow Iron Oxide, Titanium
  • Dioxide70 mgBlack Iron Oxide, Titanium Dioxide85 mgTitanium Dioxide

12.1 Mechanism Of Action

Methylphenidate HCl is a central nervous system (CNS) stimulant.
The mode of therapeutic action in ADHD is not known.

12.2 Pharmacodynamics

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

12.3 Pharmacokinetics

AbsorptionADHANSIA XR
contains a racemic mixture of d- and l-methylphenidate and produces
two distinct peak concentrations (Cmax). The 1st median (range) time to Cmax occurred at about 1.5 (1- 2.5) hours
and the 2nd about 12 (8.5- 16.0) hours
after ADHANSIA XR administration. Following administration of ADHANSIA
XR (100 mg once daily) and 60 mg of immediate-release (IR) methylphenidate
(administered as 20 mg three times daily 4 hours apart) under fasted
condition for 5 consecutive days to 21 healthy adult subjects, 1st d,l-methylphenidate mean Cmax was about 22% higher
but the 2nd mean Cmax was similar for ADHANSIA
XR compared to IR methylphenidate at steady state. The mean extent
of exposure (AUC 0-24h) and minimum concentration (Cmin) of d,l-methylphenidate
were about 50% and 288% higher, respectively for ADHANSIA XR compared
to IR methylphenidate at steady state. (Figure 1). Following administration
of ADHANSIA XR (100 mg once daily), the steady-state was reached from
day 3.Figure
1: Mean Concentration-Time Profiles for d,l-Methylphenidate on Day
5 After Daily DosingEffect of FoodHigh fat, high caloric meal (800 to 1000 calories) does not affect
Cmax and extent of absorption (AUC) of d,l-methylphenidate when taken
with ADHANSIA XR. The time to 1st and 2nd Cmax was increased by about 1 hour after administration
with a high fat meal compared to under fasting condition. The absorption
and exposure to d, l-methylphenidate were similar when ADHANSIA XR
(100 mg) was administered following an overnight fast as an intact
capsule or sprinkled on a tablespoonful of applesauce and yogurt in
healthy adult subjects.Effect of AlcoholIn vitro studies were conducted to explore the effect of alcohol on the release
characteristics of methylphenidate from ADHANSIA XR. No increase in
the rate of release of methylphenidate from ADHANSIA XR was observed
with the alcohol concentrations of 5%, 20%, and 40% at hour 1 and
for 5% and 20% at hour 2. A faster release, 71% and 61% for 70 mg
and 100 mg, respectively, was observed with the alcohol concentration
of 40% at hour 2.In an in vivo alcohol interaction study, in fasted
healthy adults, ADHANSIA XR 70 mg extended-release capsules with 40%
alcohol concentration resulted in a 1.4-fold increase in the peak
plasma methylphenidate concentration and a 1.3-fold increase in the
extent of absorption.EliminationThe mean plasma elimination
half-life for d, l-methylphenidate was about 7 hours in healthy volunteers.MetabolismIn humans, methylphenidate is metabolized primarily via deesterification
to alpha-phenyl-piperidine acetic acid (PPAA). The metabolite has
little or no pharmacologic activity.ExcretionAfter
oral dosing of radiolabeled methylphenidate in humans, about 90% of
the radioactivity was recovered in urine. The main urinary metabolite
was PPAA, accounting for approximately 80% of the dose.Specific PopulationsMale and Female PatientsThere
is insufficient experience with the use of ADHANSIA XR to detect gender
variations in pharmacokinetics.Racial or Ethnic GroupsThere is insufficient experience with the use of ADHANSIA
XR to detect ethnic variations in pharmacokinetics.Pediatric PatientsResults of the pharmacokinetic studies demonstrated that the pharmacokinetic
profile in pediatric patients (6 to 12 years) is comparable to the
pharmacokinetic profile in adults and pediatric patients (13 to 17
years) based on adjustment for body-weight.Pharmacokinetic studies of racemic methylphenidate
after oral administration of ADHANSIA XR has been conducted in pediatric
patients (6 to 17 years) with ADHD. Following administration of ADHANSIA
XR, the median (range) 1st and 2nd peak plasma concentration for d, l-methylphenidate
occurred in about 2 (1-4) and 10 (8-14) hours, respectively in pediatric
patients (6 to 12 years) and 2 (1 – 4) and 11(8 – 14) hours, respectively
in pediatric patients (13 to 17 years). The mean plasma elimination
half-life for d, l-methylphenidate was about 4 to 7 hours in pediatric
patients (6 to 12 years) and 5 hours in pediatric patients (13 to
17 years).Patients with Renal ImpairmentThere is no experience
with the use of ADHANSIA XR in patients with renal impairment. After
oral administration of radiolabeled methylphenidate in humans, methylphenidate
was extensively metabolized and approximately 80% of the radioactivity
was excreted in the urine in the form of ritalinic acid metabolite.
Since renal clearance is not an important route of methylphenidate
clearance, renal insufficiency is expected to have little effect on
the pharmacokinetics of ADHANSIA XR.Patients with Hepatic ImpairmentThere is no experience with the use of ADHANSIA XR in
patients with hepatic impairment.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

CarcinogenesisIn 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 2 times the
maximum recommended human dose (MRHD) of 85 mg/day given to children
on a mg/m2 basis. 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 increase
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 3 times the MRHD given to children on a mg/m2 basis.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.MutagenesisMethylphenidate 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 (CHO) cells. Methylphenidate was
negative in an in vivo mouse bone marrow micronucleus
assay.Impairment of FertilityMethylphenidate 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 of up to 160 mg/kg/day, approximately 5 times the maximum
recommended human dose of 85 mg/day given to adolescents on a mg/m2 basis.

14 Clinical Studies

Adult Patients with ADHDThe efficacy of ADHANSIA XR for the treatment of ADHD
in adults was evaluated in two randomized, double-blind, placebo-controlled
studies. A 4-week, randomized, double-blind, multi-center, placebo-controlled,
safety and efficacy study (Study 1 NCT02139124) involving adult patients
aged 18 to 72 years (n=375) who met the DSM-5 criteria for ADHD was
conducted. Patients were randomized to one of five treatment arms
with ADHANSIA XR 25, 45, 70, 100 mg, or placebo. Doses were titrated
to the randomized, fixed dose over a 2-week period and then maintained
at the assigned dose for an additional 2 weeks. The primary efficacy
endpoint was defined as the change from baseline (Visit 2, Week 1)
of the adult ADHD-Rating Scale (ADHD-5-RS) with prompts total score
at Visit 6, Week 5. ADHANSIA XR demonstrated a statistically significant
improvement for 45 mg and 100 mg compared to placebo on change of
ADHD-RS total score from baseline (Visit 2, Week 1) to Visit 6, Week
5 (Study 1 in Table 4).A randomized, double-blind, placebo-controlled, crossover design,
adult workplace environment (AWE) study (Study 2 NCT02225639) of ADHANSIA
XR was conducted in adults (18 to 58 years) who met the DSM-5 criteria
for ADHD. Subjects were titrated to an optimal dose (25 mg, 35 mg,
45 mg, 55 mg, 70 mg, 85 mg or 100 mg) of ADHANSIA XR in an open-label
phase of between 2 and 7 weeks, familiarized with study procedures
in a practice AWE session and then randomized to one of the two sequences:
(i) ADHANSIA XR to PLACEBO or (ii) PLACEBO to ADHANSIA XR, and received
one treatment for one week, followed by an AWE session, then crossed
over to the other treatment for one week, followed by a second AWE
session. Efficacy assessments were conducted at pre-dose and 1, 2,
5, 8, 11, 14, and 16 hours post-dose during the AWE sessions using
the Permanent Product Measure of Performance Total (PERMP-T) score.
PERMP-T is the combined score obtained by adding PERMP-A (number of
math problems attempted) and PERMP-C (number of math problems answered
correctly). The primary efficacy endpoint was the comparison of the
ADHANSIA XR with placebo in mean PERMP-T scores, averaged across all
timepoints on the AWE days. ADHANSIA XR demonstrated a statistically
significant improvement over placebo based on the primary efficacy
endpoint (Study 2 in Table 5). The secondary efficacy endpoints were
onset and duration of clinical effect, as assessed by the treatment
difference in PERMP-T scores at post-dose time points. ADHANSIA XR
also demonstrated statistically significant improvement over placebo
at 1, 2, 5, 8, 11 and 16 hours post-dose, but not at 14 hours post-dose.Pediatric Patients
(12 to 17 years) with ADHDThe efficacy of
ADHANSIA XR for the treatment of ADHD was evaluated in a 4-week randomized,
double-blind, multi-center, placebo-controlled, safety and efficacy
study (Study 3 NCT0213911) involving pediatric patients (12 to 17
years) (n=354) who met the DSM-5 criteria for ADHD. Patients were
randomized to one of five treatment arms with ADHANSIA XR 25, 45,
70, or 85 mg or placebo. Doses were titrated over a 2-week period
and then maintained on the fixed dose for an additional 2-weeks. The
primary efficacy endpoint was defined as the change from baseline
of the pediatric ADHD-5-RS total score from baseline (Week 1) to Visit
6, Week 5 (Study 3 in Table 4). ADHANSIA XR demonstrated a statistically
significant treatment effect compared with placebo at Visit 6, Week
5 for the 45 and 70 mg dose groups.Pediatric patients (6 to 12 years)
with ADHDThe efficacy of ADHANSIA XR for the
treatment of ADHD was evaluated in an analog classroom trial (Study
4 NCT03172481) conducted in pediatric patients 6 to 12 years of age
(n=147) who met the DSM-5 criteria for ADHD. Patients received ADHANSIA
XR 25, 35, 45, 55, 70 or 85 mg (mean dose 48 mg) during a 6-week,
open-label, dose-optimization period, followed by a 1-week, randomized,
placebo-controlled, double-blind treatment phase. After 1 week of
double-blind treatment, patients were evalu-ated at pre-dose and 1,
2, 4, 6, 8, 10, 12, and 13 hours post-dose on the analog classroom
day using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP)
rating scale, a 13-item teacher-rated scale that assesses manifestations
of ADHD in a classroom setting. The primary efficacy endpoint was
the comparison of the ADHANSIA XR with placebo in mean SKAMP-Combined
scores, averaged across 8 timepoints on the analog classroom day.
ADHANSIA XR demonstrated a statistically significant re-sponse over
placebo (Study 4 in Table 5.). The secondary efficacy endpoints were
onset and duration of clinical effect, as assessed by the treatment
difference in SKAMP-Combined scores at post-dose time points. The
SKAMP-Combined scores were also statistically significantly lower
(improved) at all time points (1, 2, 4, 6, 8, 10, 12, 13 hours) post-dose
with ADHANSIA XR compared to placebo (Figure 1).Table 4: Summary of Primary Efficacy Results from Studies
in Adults (Study 1) and Pediatric Patients 12 to 17 years (Study 3)
with ADHD n: number of subjects included in the primary efficacy
analysis set; SD: standard deviation; SE: standard error; LS Mean:
least-squares mean; CI: confidence interval, not adjusted for multiple
comparisons.a Difference (drug
minus placebo) in least-squares mean change from baseline.* Doses that are statistically significantly different from placebo
after adjusting for multiplicity.Study NumberTreatment
Group (ADHANSIA XR dose level)Primary
Efficacy Measure: Change from Baseline (Week 1, Visit 2) in ADHD-5-RS
Total Score to Week 5 (Visit 6)nMean Baseline Score
(SD)LS Mean Change from
Baseline (SE)Placebo-subtracted
Differencea (95% CI)Study 125 mg7536.1 (8.1)-11.6 (1.31)-1.9 (-5.6, 1.7)45 mg*7336.5 (7.2)-16.8 (1.34)-7.1 (-10.8, -3.4)70 mg7135.4 (7.4)-12.0 (1.37)-2.3 (-6.0, 1.4)100 mg*7237.0 (7.9)-17.6 (1.39)-7.9 (-11.6, -4.1)Placebo7735.7 (8.4)-9.7 (1.32)--Study 325 mg7137.7 (8.7)-12.8 (1.35)-2.2 (-5.9, 1.6)45 mg*6836.4 (8.5)-16.0 (1.39)-5.4 (-9.2, -1.6)70 mg*7235.9 (8.4)-15.8 (1.35)-5.2 (-9.0, -1.4)85 mg7037.8 (8.1)-15.0 (1.39)-4.4 (-8.2, -0.6)Placebo7137.3 (8.4)-10.6 (1.35)--Table 5: Summary of Primary Efficacy Results from Laboratory
Classroom Studies in Adults (Study 2) and Pediatric Patients 6 to
12 years (Study 4) with ADHDn: number of subjects in the primary efficacy analysis
set; SD: standard deviation; SE: standard error; LS Mean: least-squares
mean; CI: confidence interval, not adjusted for multiple comparisons.a Difference (drug minus placebo) in
least-squares mean of post-dose scores.Study NumberPrimary Efficacy MeasureTreatment GroupnPre-dose Mean Score
(SD)Post-Dose LS Mean
Score (SE)Placebo-subtracted
Differencea (95% CI)Study 2Average PERMPADHANSIA XR45225.1 (76.7)281.3 (4.33)26.80 (15.19, 38.41)Placebo45235.7 (65.4)254.5 (4.63)--Study 4Average SKAMPADHANSIA XR7414.4 (10.6)10.3 (0.74)-8.6 (-10.6, -6.6)Placebo7311.5 (7.1)18.9 (0.73) Figure 2: LS Mean
SKAMP-Combined Score after Treatment with ADHANSIA XR or Placebo during
Classroom Day in Pediatric Patients 6 to 12 years with ADHD (Study
4)LS = Least squares.SE = Standard
Error.The raw mean and SE bars are presented at the pre-dose
timepoint, rather than the LS mean and SE bars.

16 How Supplied/Storage And Handling

  • ADHANSIA XR (methylphenidate hydrochloride) extended-release capsules
  • Are available as follows:25 mg Capsules – blue, (imprinted
  • With “MLR-02” and “25 mg”)Bottles of 100 .........................................………………………………NDC
  • 72912-525-1035 mg Capsules – orange, (imprinted
  • With “MLR-02” and “35 mg”)Bottles of 100 .........................................………………………………NDC
  • 72912-535-1045 mg Capsules – yellow, (imprinted
  • With “MLR-02” and “45 mg”)Bottles of 100 ..........................................………………………….......NDC
  • 72912-545-1055 mg Capsules – light green,
  • (imprinted with “MLR-02” and “55 mg”)Bottles of 100 .........................................………………………………NDC
  • 72912-555-1070 mg Capsules – iron gray,
  • (imprinted with “MLR-02” and “70 mg”)Bottles of 100 .........................................………………………………NDC
  • 72912-570-1085 mg Capsules – white, (imprinted
  • With “MLR-02” and “85 mg”)Bottles of 100 .........................................…………………………...….NDC
  • 72912-585-10Storage and
  • HandlingStore between 20º C to 25º C (68º
  • F to 77º F); excursions permitted from 15º C to 30º C (59º F to 86º
  • F) [see USP Controlled Room Temperature]. Protect from light and moisture.Dispense in tight container
  • (USP).DisposalComply with local laws and regulations
  • On drug disposal of CNS stimulants. Dispose of remaining, unused,
  • Or expired ADHANSIA XR by a medicine take-back program or by an authorized
  • Collector registered with the Drug Enforcement Administration. If
  • No take-back program or authorized collector is available, mix ADHANSIA
  • XR with an undesirable, nontoxic substance to make it less appealing
  • To children and pets. Place the mixture in a container such as a sealed
  • Plastic bag and discard ADHANSIA XR in the household trash.

17 Patient Counseling Information

  • Advise the patient to read the FDA-approved patient
  • Labeling (Medication Guide).Controlled Substance Status/High
  • Potential for Abuse and DependenceAdvise patients
  • And their caregivers that ADHANSIA XR is a federally controlled substance,
  • And it can be abused and lead to dependence [see Drug Abuse
  • And Dependence (9.1, 9.2, and 9.3)]. Instruct patients that they should not give ADHANSIA
  • XR to anyone else. Advise patients to store ADHANSIA XR in a safe
  • Place, preferably locked, to prevent abuse. Advise patients and their
  • Caregivers to comply with laws and regulations on drug disposal.
  • Advise patients and their caregivers to dispose of remaining, unused,
  • Or expired ADHANSIA XR by a medicine take-back program if available [Warnings and Precautions (5.1),
  • Abuse and Dependence (9.2, 9.3), How Supplied/Storage and Handling
  • (16)].Instructions for Taking ADHANSIA
  • XRAdvise patients and their caregivers that
  • ADHANSIA XR can be taken with or without food. For patients who take
  • ADHANSIA XR sprinkled over a tablespoon of applesauce or yogurt, the
  • Contents of the entire capsule should be consumed immediately or within
  • 10 minutes of mixing; it should not be stored. Patients should take
  • The applesauce or yogurt with sprinkled beads in its entirety without
  • Chewing. When initiating treatment with ADHANSIA XR, provide dosage
  • Escalation and administration instructions [see Dosage and
  • Administration (2.2)].Serious Cardiovascular
  • RisksAdvise patients, caregivers, and their
  • Family members that there is a potential serious cardiovascular risk
  • Including sudden death, myocardial infarction, and stroke with ADHANSIA
  • XR 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)].Blood
  • Pressure and Heart Rate IncreasesAdvise patients
  • And their caregivers that ADHANSIA XR can cause elevations of their
  • Blood pressure and pulse rate [see Warnings and Precautions
  • (5.3)].Psychiatric RisksAdvise patients and their caregivers that ADHANSIA XR,
  • 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)].PriapismAdvise patients, caregivers, and
  • Family members of the possibility of painful or prolonged penile erections
  • (priapism). Instruct them 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]Instruct patients 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 physician 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 ADHANSIA XR. Further clinical evaluation (e.g., rheumatology referral)
  • May be appropriate for certain patients [see Warnings and
  • Precautions (5.6)].Suppression
  • Of GrowthAdvise patients, families and caregivers
  • That ADHANSIA XR may cause slowing of growth and weight loss [see Warnings and Precautions (5.7)].Alcohol EffectAdvise patients to avoid alcohol
  • While taking ADHANSIA XR. Consumption of alcohol while taking ADHANSIA
  • XR may result in a more rapid release of the dose of methylphenidate [see Clinical Pharmacology (12.3)]. Pregnancy RegistryAdvise patients that there
  • Is a pregnancy exposure registry that monitors pregnancy outcomes
  • In women exposed to ADHANSIA XR during pregnancy [see Use
  • In Specific Populations (8.1)].Marketed
  • By:Adlon Therapeutics L.P.Stamford,
  • CT 06901-3431A subsidiary of Purdue Pharma L.P.Jointly Manufactured
  • By:Glatt Air Techniques, Inc.Ramsey,
  • NJ 07446andPurdue Pharmaceuticals L.P.Wilson, NC 27893ADHANSIA XR™ is a trademark of Purdue Pharma L.P.U.S.
  • Patent Numbers: 9,974,752 and 10,111,839

Spl Medguide

  • This Medication Guide has been approved by the U.S. Food and Drug
  • Administration.
  • Issued: February/2019MEDICATION GUIDEADHANSIA (ad han' see ah) XRTM(methylphenidate hydrochloride)extended-release capsules, CIIWhat is the
  • Most important information I should know about ADHANSIA XR?ADHANSIA XR can cause serious side effects, including:Abuse and dependence. ADHANSIA XR, other methylphenidate
  • Containing medicines, and amphetamines have a high chance for abuse
  • And can cause physical and psychological dependence. Your healthcare
  • Provider should check you or your child for signs of abuse and dependence
  • Before and during treatment with ADHANSIA XR.Tell your healthcare provider if you or your child have
  • Ever abused or been dependent on alcohol, prescription medicines,
  • Or street drugs.Your healthcare provider can tell you more about the differences
  • Between physical and psychological dependence and drug addiction.Heart-related problems, including:sudden death, stroke, and heart attack in adultssudden death in children who have heart problems or heart
  • Defectsincreased blood pressure and heart rateYour healthcare provider should check you or your child carefully
  • For heart problems before starting treatment with ADHANSIA XR. Tell
  • Your healthcare provider if you or your child have any heart problems,
  • Heart defects, high blood pressure, or have a family history of these
  • Problems.Your healthcare provider should check your or
  • Your child’s blood pressure and heart rate regularly during treatment
  • With ADHANSIA XR.Call your healthcare provider or
  • Go to the nearest hospital emergency room right away if you or your
  • Child have any signs of heart problems such as chest pain, shortness
  • Of breath, or fainting during treatment with ADHANSIA XR.Mental (psychiatric) problems, including:new or worse behavior and thought problemsnew or worse bipolar illnessnew psychotic symptoms (such as hearing voices, or seeing
  • Or believing things that are not real) or new manic symptomsTell your healthcare provider about any mental problems you
  • Or your child have, or about a family history of suicide, bipolar
  • Illness, or depression.Call your healthcare provider
  • Right away if you or your child have any new or worsening mental symptoms
  • Or problems during treatment with ADHANSIA XR, especially hearing
  • Voices, seeing or believing things that are not real, or new manic
  • Symptoms.What is ADHANSIA
  • XR?ADHANSIA XR is a central nervous system (CNS)
  • Stimulant prescription medicine used for the treatment of Attention
  • Deficit Hyperactivity Disorder (ADHD) in people 6 years of age and
  • Older. ADHANSIA XR may help increase attention and decrease impulsiveness
  • And hyperactivity in people with ADHD.It is not known
  • If ADHANSIA XR is safe and effective in children under 6 years of
  • Age.ADHANSIA XR is a federally controlled substance
  • (CII) because it contains methylphenidate that can be a target for
  • People who abuse prescription medicines or street drugs. Keep
  • ADHANSIA XR in a safe place to protect it from theft. Never give your
  • ADHANSIA XR to anyone else, because it may cause death or harm them.
  • Selling or giving away ADHANSIA XR may harm others and is against
  • The law.Do not take
  • ADHANSIA XR if you or your child are:allergic to methylphenidate hydrochloride or any of the
  • Ingredients in ADHANSIA XR. See the end of this Medication Guide for
  • A complete list of ingredients in ADHANSIA XR.taking, or have stopped taking within the past 14 days,
  • A medicine used to treat depression called a monoamine oxidase inhibitor
  • (MAOI).Before taking
  • ADHANSIA XR tell your healthcare provider about all medical conditions,
  • Including if you or your child:have heart problems, heart defects, or high blood pressurehave mental problems including psychosis, mania, bipolar
  • Illness, or depression, or have a family history of suicide, bipolar
  • Illness, or depression have circulation problems in fingers and toesare pregnant or plan to become pregnant. It is not known
  • If ADHANSIA XR will harm the unborn baby. There is a pregnancy registry for females who are exposed
  • To ADHANSIA XR during pregnancy. The purpose of the registry is to
  • Collect information about the health of females exposed to ADHANSIA
  • XR and their baby. If you or your child becomes pregnant during treatment
  • With ADHANSIA XR, talk to your healthcare provider about registering
  • With the National Pregnancy Registry for Psychostimulants at 1-866-961-2388.are breastfeeding or plan to breastfeed. ADHANSIA XR passes
  • Into breast milk. Talk to your healthcare provider about the best
  • Way to feed the baby during treatment with ADHANSIA XR.Tell your healthcare provider about all the medicines
  • That you or your child take, including prescription and over-the-counter
  • Medicines, vitamins, and herbal supplements.ADHANSIA XR
  • And some medicines may interact with each other and cause serious
  • Side effects. Sometimes the doses of other medicines will need to
  • Be changed during treatment with ADHANSIA XR. Your healthcare provider
  • Will decide whether ADHANSIA XR can be taken with other medicines.Especially tell your healthcare provider if you or your child
  • Take a medicine used to treat depression called a monoamine
  • Oxidase inhibitor (MAOI).Know the medicines that you or
  • Your child take. Keep a list of the medicines with you to show your
  • Healthcare provider and pharmacist. Do not start any new medicine
  • During treatment with ADHANSIA XR without talking to your healthcare
  • Provider first.How should
  • ADHANSIA XR be taken?Take ADHANSIA XR exactly as prescribed by your healthcare
  • Provider. Your healthcare provider may change the dose if needed.Take ADHANSIA XR by mouth 1 time each day in the morning. ADHANSIA XR can be taken with or without food, but take
  • It the same way each time.Swallow ADHANSIA XR capsules whole. If ADHANSIA XR capsules
  • Cannot be swallowed whole, the capsules may be opened and sprinkled
  • Onto a tablespoonful of applesauce or yogurt. Make sure to sprinkle
  • All the medicine onto the applesauce or yogurt. The ADHANSIA XR dose
  • Should not be divided.swallow all the applesauce or yogurt and medicine mixture
  • Without chewing right away or within 10 minutesdo not chew the applesauce or yogurtdo not store applesauce or yogurt and medicine
  • MixtureYour healthcare provider may sometimes stop ADHANSIA XR
  • Treatment for a while to check ADHD symptoms.If a dose of ADHANSIA XR is missed do not take the dose
  • Later in the day or take an extra dose to make up for the missed dose,
  • Wait until the next morning to take the next scheduled dose.In case of poisoning call your poison control center
  • At 1-800-222-1222 or go to the nearest hospital emergency room right
  • Away.What should
  • Be avoided during treatment with ADHANSIA XR?Avoid
  • Drinking alcohol during treatment with ADHANSIA XR. This may cause
  • A faster release of the ADHANSIA XR medicine.What are possible
  • Side effects of ADHANSIA XR?ADHANSIA XR can
  • Cause serious side effects, including:See “What is the most important information I should
  • Know about ADHANSIA XR?”Painful and prolonged erections (priapism). Priapism has happened in males who take products that contain methylphenidate. If you or your child develop priapism, get medical help right away.Circulation problems in fingers and toes (peripheral
  • Vasculopathy, including Raynaud’s phenomenon). Signs and symptoms
  • May include:fingers or toes may feel numb, cool, painfulfingers or toes may change color from pale, to blue, to
  • RedTell your healthcare provider if you or your child have numbness,
  • Pain, skin color change, or sensitivity to temperature in the fingers
  • Or toes.Call your healthcare provider right away if your
  • Child have any signs of unexplained wounds appearing on fingers or
  • Toes during treatment with ADHANSIA XR.Slowing of growth (height and weight) in children. Children should have their height and weight checked often while
  • Taking ADHANSIA XR. ADHANSIA XR treatment may be stopped if your
  • Child is not growing or gaining weight.FD&C Yellow No. 5. ADHANSIA XR 45 mg capsules
  • Contain FD&C Yellow No. 5 (tartrazine) which may cause allergic-type
  • Reactions (including bronchial asthma) in certain people, especially
  • People who also have an allergy to aspirin.The most common side effects in adults include trouble sleeping, dry mouth, and decreased appetite.The most common side effects of ADHANSIA XR in children include decreased appetite, trouble sleeping, and decreased weight.Call your doctor for medical advice about side effects. You may
  • Report side effects to FDA at 1-800-FDA-1088.How should
  • I store ADHANSIA XR?Store ADHANSIA XR at room temperature between 68°F to 77°F
  • (20°C to 25°C).Store ADHANSIA XR in a safe place, like a locked cabinet.
  • Protect from light and moisture.Dispose of remaining, unused, or expired ADHANSIA XR by
  • A medication take-back program at authorized collection sites such
  • As retail pharmacies, hospital or clinic pharmacies, and law enforcement
  • Locations. If no take-back program or authorized collector is available,
  • Mix ADHANSIA XR with an undesirable, nontoxic substance such as dirt,
  • Cat litter, or used coffee grounds to make it less appealing to children
  • And pets. Place the mixture in a container such as a sealed plastic
  • Bag and throw away ADHANSIA XR in the household trash.Keep ADHANSIA XR and all medicines out of the reach of
  • Children.General information
  • About the safe and effective use of ADHANSIA XR.Medicines are sometimes prescribed for purposes other than those
  • Listed in a Medication Guide. Do not use ADHANSIA XR for a condition
  • For which it was not prescribed. Do not give ADHANSIA XR to other
  • People, even if they have the same symptoms. It may harm them and
  • It is against the law. You can ask your healthcare provider or pharmacist
  • For information about ADHANSIA XR that was written for healthcare
  • Professionals.What are the
  • Ingredients in ADHANSIA XR?Active Ingredient: methylphenidate hydrochlorideInactive Ingredients: ammonio methacrylate copolymer dispersion (type B), anionic copolymer
  • (consisting of methyl acrylate, methyl methacrylate and methacrylic
  • Acid), glyceryl monostearate, hypromellose, poylethylene glycol, polysorbate,
  • Silicon dioxide, sodium hydroxide, sodium laurylsulfate, sorbic acid,
  • Sugar spheres, triethyl citrateJointly Manufactured
  • By: Glatt Air Techniques, Inc., Ramsey, NJ 07466 and Purdue
  • Pharmaceuticals L.P., Wilson, NC 27893To
  • Report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at
  • 1-888-726-7535 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

* Please review the disclaimer below.

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