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 )] .
ADHANSIA XR ® 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 )] .
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 ab...
ADHANSIA XR ® (methylphenidate hydrochloride) extended-release capsules are available as follows: 25 mg Capsules – blue, (imprinted with “MLR-02” and “25 mg”) Bottles of 30 .........................................………………………………NDC 72912-525-30 35 mg Capsules – orange, (imprinted with “MLR-02” and “35 mg”) Bottles of 30 .........................................………………………………NDC 72912-535-30 45 mg Capsules – yellow, (i...
www.fda.gov/medwatchCNS 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)].
ADHANSIA XR® 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)].
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)].
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.
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.
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)].
ADHANSIA XR is contraindicated in patients:
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)].
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 ADHANSIA XR treatment.
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.
Exacerbation of Pre-Existing Psychosis
CNS 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 Disorder
CNS
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
Symptoms
CNS 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.
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.
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.
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.
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)].
The following are discussed in more detail in other sections of the labeling:
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 ADHD
Commonly 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 XR
ADHANSIA 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 three 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 two 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 1168; this included 719 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 Treatment
In 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 an adult laboratory classroom study (Study 5), 3.5% of ADHANSIA XR-treated patients discontinued due to adverse reactions during the open-label titration period. There were no discontinuations due to adverse reactions during the double-blind period of the study.
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 ADHANSIA XR-treated patients discontinued due to adverse reactions compared to 0% of placebo-treated patients.
Adult Patients with ADHD
The most common adverse reactions (incidence of ≥5% and
at least twice placebo) of ADHANSIA XR occurring in controlled trials
in adults (Study 1) 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 in Study 1.
| Adverse Reaction | ADHANSIA XR | All doses ADHANSIA XR | Placebo | |||
| 25 mg | 45 mg | 70 mg | 100 mg | |||
| N=375 | (N=77) | (N=73) | (N=73) | (N=74) | (N=297) | (N=78) |
| Initial Insomnia | 4% | 8% | 6% | 7% | 6% | 1% |
| Insomnia | 17% | 11% | 16% | 19% | 16% | 4% |
| Dry mouth | 8% | 8% | 7% | 14% | 9% | 4% |
| Nausea | 4% | 6% | 4% | 11% | 6% | 3% |
| Diarrhea | 1% | 3% | 7% | 5% | 4% | 1% |
| Decreased appetite | 4% | 7% | 15% | 19% | 11% | 3% |
| Feeling jittery | 1% | 3% | 8% | 4% | 4% | 1% |
| Weight decreased | 3% | 4% | 3% | 5% | 4% | 1% |
| Upper respiratory tract infection | 0% | 4% | 3% | 3% | 2% | 1% |
The most common adverse reactions (incidence of ≥5%) of ADHANSIA XR occurring in adults in the open-label dose-optimization period of Study 5 were headache, decreased appetite, insomnia, irritability, upper respiratory tract infection, dry mouth, nausea, anxiety, and fatigue.
Table 2 lists adverse reactions that occurred ≥2% of adult patients in the ADHANSIA XR-treated patients and greater than placebo-treated patients for the double-blind period of study 5.
| * Includes insomnia, initial insomnia, and delayed sleep phase | |||||||||
| Adverse Reaction | ADHANSIA XR | All doses ADHANSIA XR | Placebo | ||||||
| 25 mg | 35 mg | 45 mg | 55 mg | 70 mg | 85 mg | 100 mg | |||
| N=239 | (N=3) | (N=4) | (N=15) | (N=31) | (N=30) | (N=22) | (N=16) | (N=121) | (N=118) |
| Headache | 0% | 0% | 7% | 0% | 3% | 5% | 13% | 4% | 3% |
| Fatigue | 0% | 0% | 0% | 3% | 3% | 9% | 0% | 3% | 1% |
| Insomnia* | 0% | 0% | 0% | 0% | 7% | 5% | 0% | 3% | 2% |
| Irritability | 0% | 0% | 0% | 0% | 0% | 9% | 0% | 2% | 0% |
| Nausea | 0% | 0% | 7% | 3% | 0% | 0% | 0% | 2% | 0% |
| Dysmenorrhea | 0% | 25% | 0% | 0% | 0% | 5% | 0% | 2% | 0% |
Pediatric
Patients (12 to 17 years) with ADHD
The 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 3 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).
| Adverse Reaction | ADHANSIA XR | All doses ADHANSIA XR | Placebo | |||
| 25 mg | 45 mg | 70 mg | 85 mg | |||
| (N=73) | (N=72) | (N=76) | (N=72) | (N=293) | (N=74) | |
| Decreased appetite | 7% | 19% | 28% | 26% | 20% | 0% |
| Insomnia | 4% | 0% | 9% | 13% | 6% | 1% |
| Initial Insomnia | 4% | 7% | 5% | 4% | 5% | 1% |
| Weight decreased | 1% | 3% | 8% | 13% | 7% | 0% |
| Abdominal pain upper | 5% | 1% | 5% | 4% | 4% | 1% |
| Nausea | 3% | 6% | 7% | 8% | 6% | 4% |
| Dizziness | 3% | 0% | 4% | 4% | 3% | 0% |
| Dry mouth | 1% | 0% | 5% | 4% | 3% | 1% |
| Vomiting | 1% | 1% | 3% | 6% | 3% | 0% |
Pediatric
Patients (6 to 12 years) with ADHD
Study 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.
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 purpura
Cardiac Disorders: angina pectoris, bradycardia, extrasystole, supraventricular tachycardia, ventricular extrasystole
Eye Disorders: diplopia, mydriasis, visual impairment
General Disorders: chest pain, chest discomfort, hyperpyrexia
Hepatobiliary disorders: hepatocellular injury, acute hepatic failure
Immune 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, rhabdomyolysis
Nervous System Disorders: convulsion, grand mal convulsion, dyskinesia, serotonin syndrome in combination with serotonergic drugs
Psychiatric Disorders: disorientation, hallucination, hallucination auditory, hallucination visual, libido changes, logorrhea, mania
Skin and Subcutaneous Tissue Disorders: alopecia, erythema
Urogenital System: priapism
Vascular Disorders: Raynaud’s phenomenon
Table 3 presents clinically important drug interactions with ADHANSIA XR.
| 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 ADHANSIA XR concomitantly with MAOIs or within 14 days after discontinuing MAOI treatment. |
| Examples: | selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue |
| Gastric pH Modulators | |
| Clinical 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 |
| Antihypertensive Drugs | |
| Clinical Impact: | ADHANSIA XR 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. |
| Examples: | Potassium-sparing and thiazide diuretics, calcium channel blockers, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta blockers, centrally acting alpha-2 receptor agonists |
| 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. |
Pregnancy Exposure Registry
There 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 Summary
Published 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 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 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 Considerations
Fetal/Neonatal Adverse Reactions
CNS 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.
Data
Animal Data
In 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).
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. 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 Considerations
Monitor
breastfeeding infants for adverse reactions, such as agitation, anorexia,
and reduced weight gain.
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 Growth
Growth 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 Data
Rats 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.
ADHANSIA XR has not been studied in the patients over the age of 72 years.
ADHANSIA XR contains methylphenidate, a Schedule II controlled substance.
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.
Dependence
ADHANSIA XR may produce physical
dependence from continued therapy. Physical dependence is a state
of adaptation manifested by a withdrawal syndrome produced by abrupt
cessation, rapid dose reduction, or administration of an antagonist.
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.
Tolerance
ADHANSIA XR may produce tolerance from continued therapy. Tolerance
is 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.
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, hyperreflexia, 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.
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.
ADHANSIA XR extended-release capsules contain 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.
ADHANSIA XR is intended for oral administration. 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-piperidine acetate 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, polyethylene glycol, polysorbate, silicon dioxide, sodium hydroxide, sodium lauryl sulfate, sorbic acid, sugar spheres, triethyl citrate.
Each strength capsule also contains colorant ingredients in the capsule shell as follows:
Methylphenidate HCl is a central nervous system (CNS) stimulant. The mode of therapeutic action in ADHD is not known.
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.
Absorption
ADHANSIA 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 (AUC0-24h) 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 Dosing
Effect of Food
High 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 Alcohol
In 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.
Elimination
The mean plasma elimination
half-life for d, l-methylphenidate was about 7 hours in healthy volunteers.
Metabolism
In humans, methylphenidate is metabolized primarily via de-esterification
to alpha-phenyl-piperidine acetic acid (PPAA). The metabolite has
little or no pharmacologic activity.
Excretion
After
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 Populations
Male and Female Patients
There
is insufficient experience with the use of ADHANSIA XR to detect gender
variations in pharmacokinetics.
Racial or Ethnic Groups
There is insufficient experience with the use of ADHANSIA
XR to detect ethnic variations in pharmacokinetics.
Pediatric Patients
Results 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 Impairment
There 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 Impairment
There is no experience with the use of ADHANSIA XR in
patients with hepatic impairment.
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 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.
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 (CHO) cells. Methylphenidate was
negative in an in vivo 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 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.
Adult Patients with ADHD
The efficacy of ADHANSIA XR for the treatment of ADHD
in adults was evaluated in three 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 demonstrated statistically significant improvement over placebo at 1, 2, 5, 8, 11 and 16 hours post-dose, but not at 14 hours post-dose.
A randomized, double-blind, placebo-controlled, parallel-group, adult laboratory classroom (ALC) study (Study 5 NCT03618030) of ADHANSIA XR was conducted in adults (18 to 60 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, mean dose 67.5 mg) of ADHANSIA XR in an open-label phase for up to 7 weeks, familiarized with study procedures in a practice ALC session, then randomized to their optimal dose of ADHANSIA XR or placebo. At the end of 1 week of double-blind treatment, patients were evaluated at pre-dose and at 0.5, 1, 2, 4, 6, 7.5, 9, 11, 13, 14, 15, and 16 hours post-dose during the ALC session using the Permanent Product Measure of Performance Total (PERMP-T) score.
The primary efficacy endpoint was the comparison of the ADHANSIA XR with placebo in mean PERMP-T scores, averaged across all timepoints on the ALC day. ADHANSIA XR demonstrated a statistically significant improvement over placebo based on the primary efficacy endpoint (Study 5 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 demonstrated statistically significant improvement over placebo at 1, 2, 4, 6, 7.5, 9, 11, 13, 14, 15, and 16 hours post- dose.
Pediatric Patients (12 to 17 years) with ADHD
The 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 NCT02139111)
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 ADHD
The 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-con- trolled, double-blind treatment
phase. After 1 week of double-blind treatment, patients were evaluated
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
response 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 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 2).
| 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 Number | Treatment 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) | |||
| n | Mean Baseline Score (SD) | LS Mean Change from Baseline (SE) | Placebo-subtracted Differencea (95% CI) | ||
| Study 1 | 25 mg | 75 | 36.1 (8.1) | -11.6 (1.31) | -1.9 (-5.6, 1.7) |
| 45 mg* | 73 | 36.5 (7.2) | -16.8 (1.34) | -7.1 (-10.8, -3.4) | |
| 70 mg | 71 | 35.4 (7.4) | -12.0 (1.37) | -2.3 (-6.0, 1.4) | |
| 100 mg* | 72 | 37.0 (7.9) | -17.6 (1.39) | -7.9 (-11.6, -4.1) | |
| Placebo | 77 | 35.7 (8.4) | -9.7 (1.32) | -- | |
| Study 3 | 25 mg | 71 | 37.7 (8.7) | -12.8 (1.35) | -2.2 (-5.9, 1.6) |
| 45 mg* | 68 | 36.4 (8.5) | -16.0 (1.39) | -5.4 (-9.2, -1.6) | |
| 70 mg* | 72 | 35.9 (8.4) | -15.8 (1.35) | -5.2 (-9.0, -1.4) | |
| 85 mg | 70 | 37.8 (8.1) | -15.0 (1.39) | -4.4 (-8.2, -0.6) | |
| Placebo | 71 | 37.3 (8.4) | -10.6 (1.35) | -- | |
| n: 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. b In each treatment group, three subjects did not have a pre-dose score. Hence, the actual numbers of patients included in the primary analysis were 113 and 110 respectively. | ||||||
| Study Number | Primary Efficacy Measure | Treatment Group | n | Pre-dose Mean Score (SD) | Post-Dose LS Mean Score (SE) | Placebo-subtracted Differencea (95% CI) |
| Study 2 | Average PERMP-T | ADHANSIA XR | 45 | 225.1 (76.7) | 281.3 (4.33) | 26.80 (15.19, 38.41) |
| Placebo | 45 | 235.7 (65.4) | 254.5 (4.63) | -- | ||
| Study 5 | Average PERMP-T | ADHANSIA XR | 116b | 258.2 (89.2) | 302.9 (3.50) | 16.3 (7.6, 24.9) |
| Placebo | 113b | 275.2 (105.8) | 286.6 (3.52) | – | ||
| Study 4 | Average SKAMP-C | ADHANSIA XR | 74 | 14.4 (10.6) | 10.3 (0.74) | -8.6 (-10.6, -6.6) |
| Placebo | 73 | 11.5 (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.
ADHANSIA XR® (methylphenidate hydrochloride) extended-release capsules are available as follows:
Storage and
Handling
Store 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).
Disposal
Comply 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.
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Controlled Substance Status/High Potential for Abuse and
Dependence
Advise 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)].
Serious Cardiovascular Risks
Advise 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 Increases
Advise patients and their caregivers that ADHANSIA XR can cause
elevations of their blood pressure and pulse rate [see Warnings
and Precautions (5.3)].
Psychiatric Risks
Advise 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)].
Priapism
Advise 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]
Suppression
of Growth
Advise patients, families and caregivers
that ADHANSIA XR may cause slowing of growth and weight loss [see Warnings and Precautions (5.7)].
Administration Instructions
Advise 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)].
Alcohol Effect
Advise 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 Registry
Advise 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 06901-3431
A
subsidiary of Purdue Pharma L.P.
Manufactured by:
Purdue Pharmaceuticals L.P.
Wilson, NC 27893
ADHANSIA XR® is a registered trademark of Purdue Pharma L.P.
U.S. Patent Numbers:
9,974,752; 10,111,839; 10,292,938; 10,292,939; 10,449,159; 10,500,162;
10,507,186; 10,512,612; 10,512,613; 10,568,841; 10,688,060 and 10,722,473
| This Medication Guide has been approved by the U.S. Food and Drug Administration. | Revised 6/2021 |
| MEDICATION GUIDE ADHANSIA (ad han' see ah) XR® (methylphenidate hydrochloride) extended-release capsules, CII | |
| What is the
most important information I should know about ADHANSIA XR? ADHANSIA XR can cause serious side effects, including:
| |
| 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:
| |
Before taking
ADHANSIA XR tell your healthcare provider about all medical conditions,
including if you or your child:
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?
| |
| 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:
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?
| |
| 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 hydrochloride Inactive Ingredients: ammonio methacrylate copolymer dispersion (type B), anionic copolymer (consisting of methyl acrylate, methyl methacrylate and methacrylic acid), glyceryl monostearate, hypromellose, polyethylene glycol, polysorbate, silicon dioxide, sodium hydroxide, sodium lauryl sulfate, sorbic acid, sugar spheres, triethyl citrate Manufactured by: Purdue Pharmaceuticals L.P., Wilson, NC 27893 To 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. | |
ADHANSIA
XR 25 mg
NDC: 72912-525-30
ADHANSIA
XR 35 mg
NDC: 72912-535-30
ADHANSIA
XR 45 mg
NDC: 72912-545-30
ADHANSIA
XR 55 mg
NDC: 72912-555-30
ADHANSIA
XR 70 mg
NDC: 72912-570-30
ADHANSIA
XR 85 mg
NDC: 72912-585-30
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 72912-535-30 | EA - Each | 72912-535 | da2bd3e2-c307-4265-af20-9b18d3ce279d | 1 | 2019-07-02 |
| 72912-585-30 | EA - Each | 72912-585 | 9e23153e-9ec9-4a33-9d30-c0eb77f65671 | 1 | 2019-07-02 |
| 72912-525-30 | EA - Each | 72912-525 | c9f980cf-e30d-449d-ae1f-a7fbc69c7032 | 1 | 2019-07-02 |
| 72912-545-30 | EA - Each | 72912-545 | 18369a1c-1ae4-4640-bdf1-e91d7d6701a4 | 1 | 2019-07-02 |
| 72912-570-30 | EA - Each | 72912-570 | 98b4e53c-97bf-46fe-998d-0361d9e79024 | 1 | 2019-07-02 |
| 72912-555-30 | EA - Each | 72912-555 | 5ad007d8-ebbe-40fd-bba6-a50894dff3a4 | 1 | 2019-07-02 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 72912-535 | 72912-535-30 |
| 72912-585 | 72912-585-30 |
| 72912-525 | 72912-525-30 |
| 72912-545 | 72912-545-30 |
| 72912-570 | 72912-570-30 |
| 72912-555 | 72912-555-30 |
Every source-derived ingredient row is available through these pages.
All distinct exact application/product contexts derived from this label’s complete NDC list are paginated below.
| Application-product | Trade name | Ingredient | Strength | Dosage form / route | TE codes | RLD / RS | Approval date |
|---|---|---|---|---|---|---|---|
| N212038-001 | ADHANSIA XR | METHYLPHENIDATE HYDROCHLORIDE | 25MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | |
| N212038-002 | ADHANSIA XR | METHYLPHENIDATE HYDROCHLORIDE | 35MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | |
| N212038-003 | ADHANSIA XR | METHYLPHENIDATE HYDROCHLORIDE | 45MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | |
| N212038-004 | ADHANSIA XR | METHYLPHENIDATE HYDROCHLORIDE | 55MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | |
| N212038-005 | ADHANSIA XR | METHYLPHENIDATE HYDROCHLORIDE | 70MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | |
| N212038-006 | ADHANSIA XR | METHYLPHENIDATE HYDROCHLORIDE | 85MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 |
| Application-product | Patent | Expiration | Use code | Coverage / status | Submission date |
|---|---|---|---|---|---|
| N212038-001 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | |
| N212038-001 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | |
| N212038-001 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 |
| N212038-001 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | |
| N212038-001 | 10500162 | 2035-10-30 | U-2357 | 2019-12-11 | |
| N212038-001 | 10507186 | 2035-10-30 | Drug product | 2019-12-18 | |
| N212038-001 | 10512612 | 2035-10-30 | Drug product | 2020-01-02 | |
| N212038-001 | 10512613 | 2035-10-30 | U-2357 | 2020-01-02 | |
| N212038-001 | 10568841 | 2035-10-30 | U-2357 | Drug product | 2020-02-26 |
| N212038-001 | 10688060 | 2035-10-30 | Drug product | 2020-06-23 | |
| N212038-001 | 9974752 | 2035-10-30 | Drug product | 2019-03-08 | |
| N212038-001 | 10722473 | 2038-11-19 | U-2357 | 2020-07-28 | |
| N212038-002 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | |
| N212038-002 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | |
| N212038-002 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 |
| N212038-002 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | |
| N212038-002 | 10500162 | 2035-10-30 | U-2357 | 2019-12-11 | |
| N212038-002 | 10507186 | 2035-10-30 | Drug product | 2019-12-18 | |
| N212038-002 | 10512612 | 2035-10-30 | Drug product | 2020-01-02 | |
| N212038-002 | 10512613 | 2035-10-30 | U-2357 | 2020-01-02 | |
| N212038-002 | 10568841 | 2035-10-30 | U-2357 | Drug product | 2020-02-26 |
| N212038-002 | 10688060 | 2035-10-30 | Drug product | 2020-06-23 | |
| N212038-002 | 9974752 | 2035-10-30 | Drug product | 2019-03-08 | |
| N212038-002 | 10722473 | 2038-11-19 | U-2357 | 2020-07-28 | |
| N212038-003 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | |
| N212038-003 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | |
| N212038-003 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 |
| N212038-003 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | |
| N212038-003 | 10500162 | 2035-10-30 | U-2357 | 2019-12-11 | |
| N212038-003 | 10507186 | 2035-10-30 | Drug product | 2019-12-18 | |
| N212038-003 | 10512612 | 2035-10-30 | Drug product | 2020-01-02 | |
| N212038-003 | 10512613 | 2035-10-30 | U-2357 | 2020-01-02 | |
| N212038-003 | 10568841 | 2035-10-30 | U-2357 | Drug product | 2020-02-26 |
| N212038-003 | 10688060 | 2035-10-30 | Drug product | 2020-06-23 | |
| N212038-003 | 9974752 | 2035-10-30 | Drug product | 2019-03-08 | |
| N212038-003 | 10722473 | 2038-11-19 | U-2357 | 2020-07-28 | |
| N212038-004 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | |
| N212038-004 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | |
| N212038-004 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 |
| N212038-004 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | |
| N212038-004 | 10500162 | 2035-10-30 | U-2357 | 2019-12-11 | |
| N212038-004 | 10507186 | 2035-10-30 | Drug product | 2019-12-18 | |
| N212038-004 | 10512612 | 2035-10-30 | Drug product | 2020-01-02 | |
| N212038-004 | 10512613 | 2035-10-30 | U-2357 | 2020-01-02 | |
| N212038-004 | 10568841 | 2035-10-30 | U-2357 | Drug product | 2020-02-26 |
| N212038-004 | 10688060 | 2035-10-30 | Drug product | 2020-06-23 | |
| N212038-004 | 9974752 | 2035-10-30 | Drug product | 2019-03-08 | |
| N212038-004 | 10722473 | 2038-11-19 | U-2357 | 2020-07-28 | |
| N212038-005 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | |
| N212038-005 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | |
| N212038-005 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 |
| N212038-005 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | |
| N212038-005 | 10500162 | 2035-10-30 | U-2357 | 2019-12-11 | |
| N212038-005 | 10507186 | 2035-10-30 | Drug product | 2019-12-18 | |
| N212038-005 | 10512612 | 2035-10-30 | Drug product | 2020-01-02 | |
| N212038-005 | 10512613 | 2035-10-30 | U-2357 | 2020-01-02 | |
| N212038-005 | 10568841 | 2035-10-30 | U-2357 | Drug product | 2020-02-26 |
| N212038-005 | 10688060 | 2035-10-30 | Drug product | 2020-06-23 | |
| N212038-005 | 9974752 | 2035-10-30 | Drug product | 2019-03-08 | |
| N212038-005 | 10722473 | 2038-11-19 | U-2357 | 2020-07-28 | |
| N212038-006 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | |
| N212038-006 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | |
| N212038-006 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 |
| N212038-006 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | |
| N212038-006 | 10500162 | 2035-10-30 | U-2357 | 2019-12-11 | |
| N212038-006 | 10507186 | 2035-10-30 | Drug product | 2019-12-18 | |
| N212038-006 | 10512612 | 2035-10-30 | Drug product | 2020-01-02 | |
| N212038-006 | 10512613 | 2035-10-30 | U-2357 | 2020-01-02 | |
| N212038-006 | 10568841 | 2035-10-30 | U-2357 | Drug product | 2020-02-26 |
| N212038-006 | 10688060 | 2035-10-30 | Drug product | 2020-06-23 | |
| N212038-006 | 9974752 | 2035-10-30 | Drug product | 2019-03-08 | |
| N212038-006 | 10722473 | 2038-11-19 | U-2357 | 2020-07-28 |
Observed FDA ZIP history: Each table is queried independently by exact application/product key from successfully parsed Orange Book snapshots. Capture times identify archived source observations; absence or a change between snapshots is not inferred. FDA publication files that were not recoverable as structured ZIP data are not represented as states.
| Captured | Edition | Application-product | Trade name | Strength | Dosage form / route | Product TE source text | RLD / RS | Approval date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|---|
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | ADHANSIA XR | 25MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | ADHANSIA XR | 35MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | ADHANSIA XR | 45MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-004 | ADHANSIA XR | 55MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-005 | ADHANSIA XR | 70MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-006 | ADHANSIA XR | 85MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | c2088c7a36db… | |
| 2026-09-14 22:38:34 | 2026-08 | N212038-001 | ADHANSIA XR | 25MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N212038-002 | ADHANSIA XR | 35MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N212038-003 | ADHANSIA XR | 45MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N212038-004 | ADHANSIA XR | 55MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N212038-005 | ADHANSIA XR | 70MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 84e616aacf4f… | |
| 2026-09-14 22:38:34 | 2026-08 | N212038-006 | ADHANSIA XR | 85MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 84e616aacf4f… | |
| 2026-08-18 06:07:40 | 2026-07 | N212038-001 | ADHANSIA XR | 25MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N212038-002 | ADHANSIA XR | 35MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N212038-003 | ADHANSIA XR | 45MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N212038-004 | ADHANSIA XR | 55MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N212038-005 | ADHANSIA XR | 70MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | caaa826d4ba7… | |
| 2026-08-18 06:07:40 | 2026-07 | N212038-006 | ADHANSIA XR | 85MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | caaa826d4ba7… | |
| 2026-02-19 14:30 UTC | 2026-02 | N212038-001 | ADHANSIA XR | 25MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N212038-002 | ADHANSIA XR | 35MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N212038-003 | ADHANSIA XR | 45MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N212038-004 | ADHANSIA XR | 55MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N212038-005 | ADHANSIA XR | 70MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 011fe1cb6892… | |
| 2026-02-19 14:30 UTC | 2026-02 | N212038-006 | ADHANSIA XR | 85MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 011fe1cb6892… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N212038-001 | ADHANSIA XR | 25MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N212038-002 | ADHANSIA XR | 35MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N212038-003 | ADHANSIA XR | 45MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N212038-004 | ADHANSIA XR | 55MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N212038-005 | ADHANSIA XR | 70MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 31067a03dcf5… | |
| 2025-12-14 10:44 UTC · 2 captures of this ZIP | 2025-12 | N212038-006 | ADHANSIA XR | 85MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 31067a03dcf5… | |
| 2025-08-23 18:47 UTC | 2025-08 | N212038-001 | ADHANSIA XR | 25MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N212038-002 | ADHANSIA XR | 35MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N212038-003 | ADHANSIA XR | 45MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N212038-004 | ADHANSIA XR | 55MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N212038-005 | ADHANSIA XR | 70MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 6a471c1ec25d… | |
| 2025-08-23 18:47 UTC | 2025-08 | N212038-006 | ADHANSIA XR | 85MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | 6a471c1ec25d… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N212038-001 | ADHANSIA XR | 25MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N212038-002 | ADHANSIA XR | 35MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N212038-003 | ADHANSIA XR | 45MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | fd3edfee7708… | |
| 2025-03-22 03:13 UTC · 3 captures of this ZIP | 2025-03 | N212038-004 | ADHANSIA XR | 55MG | CAPSULE, EXTENDED RELEASE / ORAL | RLD | 2019-02-27 | fd3edfee7708… |
| Captured | Edition | Application-product | Patent | Expiration | Use code | Coverage / status | Submission date | Source SHA-256 |
|---|---|---|---|---|---|---|---|---|
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10500162 | 2035-10-30 | U-2357 | 2019-12-11 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10507186 | 2035-10-30 | Drug product | 2019-12-18 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10512612 | 2035-10-30 | Drug product | 2020-01-02 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10512613 | 2035-10-30 | U-2357 | 2020-01-02 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10568841 | 2035-10-30 | U-2357 | Drug product | 2020-02-26 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10688060 | 2035-10-30 | Drug product | 2020-06-23 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 9974752 | 2035-10-30 | Drug product | 2019-03-08 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-001 | 10722473 | 2038-11-19 | U-2357 | 2020-07-28 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10500162 | 2035-10-30 | U-2357 | 2019-12-11 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10507186 | 2035-10-30 | Drug product | 2019-12-18 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10512612 | 2035-10-30 | Drug product | 2020-01-02 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10512613 | 2035-10-30 | U-2357 | 2020-01-02 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10568841 | 2035-10-30 | U-2357 | Drug product | 2020-02-26 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10688060 | 2035-10-30 | Drug product | 2020-06-23 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 9974752 | 2035-10-30 | Drug product | 2019-03-08 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-002 | 10722473 | 2038-11-19 | U-2357 | 2020-07-28 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10500162 | 2035-10-30 | U-2357 | 2019-12-11 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10507186 | 2035-10-30 | Drug product | 2019-12-18 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10512612 | 2035-10-30 | Drug product | 2020-01-02 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10512613 | 2035-10-30 | U-2357 | 2020-01-02 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10568841 | 2035-10-30 | U-2357 | Drug product | 2020-02-26 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10688060 | 2035-10-30 | Drug product | 2020-06-23 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 9974752 | 2035-10-30 | Drug product | 2019-03-08 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-003 | 10722473 | 2038-11-19 | U-2357 | 2020-07-28 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-004 | 10111839 | 2035-10-30 | U-2357 | 2019-03-08 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-004 | 10292938 | 2035-10-30 | Drug product | 2019-05-22 | c2088c7a36db… | |
| 2026-10-15 13:18:30 | 2026-09 | N212038-004 | 10292939 | 2035-10-30 | U-2357 | Drug product | 2019-05-22 | c2088c7a36db… |
| 2026-10-15 13:18:30 | 2026-09 | N212038-004 | 10449159 | 2035-10-30 | U-2357 | 2019-10-22 | c2088c7a36db… |
| Captured | Edition | Application-product | Exclusivity code | Expiration | Source SHA-256 |
|---|---|---|---|---|---|
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N212038-001 | M-82 | 2024-06-28 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N212038-002 | M-82 | 2024-06-28 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N212038-003 | M-82 | 2024-06-28 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N212038-004 | M-82 | 2024-06-28 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N212038-005 | M-82 | 2024-06-28 | 03ed91905a0d… |
| 2025-01-19 17:59 UTC · 7 captures of this ZIP | 2025-01 | N212038-006 | M-82 | 2024-06-28 | 03ed91905a0d… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N212038-001 | M-82 | 2024-06-28 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N212038-002 | M-82 | 2024-06-28 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N212038-003 | M-82 | 2024-06-28 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N212038-004 | M-82 | 2024-06-28 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N212038-005 | M-82 | 2024-06-28 | 2680178bc6a6… |
| 2024-12-13 21:23 UTC · 2 captures of this ZIP | 2024-12 | N212038-006 | M-82 | 2024-06-28 | 2680178bc6a6… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N212038-001 | M-82 | 2024-06-28 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N212038-002 | M-82 | 2024-06-28 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N212038-003 | M-82 | 2024-06-28 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N212038-004 | M-82 | 2024-06-28 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N212038-005 | M-82 | 2024-06-28 | 5bbf6a4d5a75… |
| 2024-09-14 05:58 UTC · 2 captures of this ZIP | 2024-09 | N212038-006 | M-82 | 2024-06-28 | 5bbf6a4d5a75… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N212038-001 | M-82 | 2024-06-28 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N212038-002 | M-82 | 2024-06-28 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N212038-003 | M-82 | 2024-06-28 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N212038-004 | M-82 | 2024-06-28 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N212038-005 | M-82 | 2024-06-28 | d8e5a09893c0… |
| 2024-11-08 22:44 UTC · 3 captures of this ZIP | 2024-11 | N212038-006 | M-82 | 2024-06-28 | d8e5a09893c0… |
| 2024-10-29 15:01 UTC | 2024-10 | N212038-001 | M-82 | 2024-06-28 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N212038-002 | M-82 | 2024-06-28 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N212038-003 | M-82 | 2024-06-28 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N212038-004 | M-82 | 2024-06-28 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N212038-005 | M-82 | 2024-06-28 | d06236e962d9… |
| 2024-10-29 15:01 UTC | 2024-10 | N212038-006 | M-82 | 2024-06-28 | d06236e962d9… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N212038-001 | M-82 | 2024-06-28 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N212038-002 | M-82 | 2024-06-28 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N212038-003 | M-82 | 2024-06-28 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N212038-004 | M-82 | 2024-06-28 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N212038-005 | M-82 | 2024-06-28 | 79d66fd596c7… |
| 2024-08-13 05:28 UTC · 3 captures of this ZIP | 2024-08 | N212038-006 | M-82 | 2024-06-28 | 79d66fd596c7… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | N212038-001 | M-82 | 2024-06-28 | 301d65b070ca… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | N212038-002 | M-82 | 2024-06-28 | 301d65b070ca… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | N212038-003 | M-82 | 2024-06-28 | 301d65b070ca… |
| 2024-07-13 05:37 UTC · 2 captures of this ZIP | 2024-07 | N212038-004 | M-82 | 2024-06-28 | 301d65b070ca… |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| 44d07b63-99b3-4c9d-a0fc-935290e76059 | 80e15bd0-4d56-75f0-ab5a-885879fc56e9 | 2023-04-19 | Boxed warning, Warnings, Adverse reactions | 44d07b63-99b3-4c9d-a0fc-935290e76059 80e15bd0-4d56-75f0-ab5a-885879fc56e9 |
Adverse event summaries are temporarily unavailable. Other product information remains available.