Adhansia XR™ (methylphenidate HCl) Extended Release Capsules CII, New ADHD Treatment from Adlon Therapeutics L.P., Now Available Throughout the U.S.
In Conjunction with the New Medication Introduction, Adlon Commits to Support Responsible Use of Prescription Stimulants
Stamford, Conn., July 30, 2019 – Adlon Therapeutics L.P., a subsidiary of Purdue Pharma L.P., today announced that Adhansia XR™ (methylphenidate hydrochloride) extended-release capsules CII, a central nervous system (CNS) stimulant for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in patients six years and older, is now available in the United States.
“As part of our mission to address the medical needs of patients suffering from a variety of disease conditions and symptoms beyond chronic pain, we’re pleased to make Adhansia XR available by prescription following its approval earlier this year by the U.S. Food and Drug Administration. While Adhansia XR is not appropriate for all patients with ADHD, we believe it has the potential to address an important treatment gap for certain patients who may require a longer acting medication,” said Craig Landau, MD, president and CEO, Purdue Pharma. “With this introduction, we are simultaneously reaffirming our commitment to a variety of initiatives in support of responsible prescribing and utilization of stimulant medications. One such measure includes Adlon’s recent decision to become a member of the Prescription Drug Safety Network, a nationwide public-private coalition committed to empowering students with skills to help make safe and healthy decisions about prescription medications.”
The Full Prescribing Information for Adhansia XR contains a boxed warning for abuse and dependence. CNS stimulants, including Adhansia XR, other methylphenidate-containing products, and amphetamines have a high potential for abuse and dependence. Healthcare professionals should assess the risk of abuse prior to prescribing Adhansia XR and monitor for signs of abuse and dependence while patients are on therapy.1
Adhansia XR is not appropriate for all patients, and healthcare professionals should work with their patients to determine the most appropriate treatment option. Adhansia XR is contraindicated in patients with a known hypersensitivity to methylphenidate or product components, as well as patients receiving concurrent treatment with a monoamine oxidase inhibitor (MAOI) or who have used an MAOI within the preceding 14 days.1
The Full Prescribing Information for Adhansia XR, including Boxed Warning, is available at this link. Please see Important Safety Information for Adhansia XR below, including the Boxed Warning, Contraindications, Warnings and Precautions including the potential for abuse and dependence, serious cardiovascular events, blood pressure and heart rate increases, psychiatric adverse reactions, priapism, peripheral vasculopathy, long-term suppression of growth, allergic-type reactions, and Adverse Reactions.1
“For some patients living with ADHD, managing symptoms outside of standard work or school hours can be difficult. Adhansia XR is a new option that may help address the needs of certain patients who could benefit from a longer duration of efficacy,” said Alice Mao, MD, Memorial Park Psychiatry, Houston. “As prescription stimulant use continues to rise, it is important to remind patients and families that methylphenidate-containing medications are scheduled products and must be used responsibly.”
Availability and Dosing
Adhansia XR will be available in six capsule strengths (25, 35, 45, 55, 70, and 85 mg). The recommended starting dose of Adhansia XR for patients six years or older is 25 mg once daily. Healthcare professionals should titrate the dose in increments of 10 mg to 15 mg at intervals of no less than five 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. Adhansia XR should be taken orally once daily in the morning, with or without food. Capsules may be taken whole or, for patients who have difficulty swallowing, capsules may be opened and the entire contents sprinkled onto a tablespoon of applesauce or yogurt. The entire mixture should be consumed without crushing or chewing, immediately or within 10 minutes. If the mixture is not consumed within 10 minutes after mixing, it should be discarded and not stored. The dose of a single capsule should not be divided and patients should not take anything less than one capsule per day. In the event of a missed dose, patients should not take their medication later in the day.1
Prior to initiating treatment with Adhansia XR, healthcare professionals should assess for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam). Healthcare professionals should also assess the risk of abuse prior to prescribing Adhansia XR and monitor for signs of abuse and dependence while patients are on therapy. After prescribing and while patients are on therapy, healthcare professionals should maintain careful prescription records, educate patients and their families about abuse and proper storage and disposal of CNS stimulants, and periodically re-evaluate the need for Adhansia XR use.1
Dosages above 85 mg daily in adults and 70 mg and above daily in pediatric patients are associated with disproportionate increases in the incidence of certain adverse reactions. If paradoxical aggravation of symptoms or other adverse reactions occur, healthcare professionals should reduce the dosage, or, if necessary, discontinue treatment with Adhansia XR. Treatment with Adhansia XR should also be periodically discontinued to assess the patient’s condition. If improvement is not observed in a patient after appropriate dosage adjustment over a one-month period, healthcare providers should discontinue treatment with Adhansia XR.1
About Adhansia XR Phase 3 Clinical Trials1
The U.S. FDA approval of Adhansia XR was based on four clinical studies evaluating the efficacy and safety of Adhansia XR in patients who met DSM-5 criteria for ADHD. Eight hundred and eighty-three (883) patients were exposed to Adhansia XR during 1- to 4-week long, controlled treatment periods (434 adult patients and 449 pediatric patients [156 (6 to 12 years); 293 (12 to 17 years)] from two clinical studies in adults, one analog classroom trial over a 13-hour study day in pediatric patients ages 6 to 12 years, and one safety and efficacy study in pediatric patients ages 12 to 17 years). The safety data for adult patients are 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) are based on randomized, double-blind, placebo-controlled studies in doses of 25 mg to 85 mg per day.
A double-blind, randomized, placebo-controlled crossover adult workplace environment (AWE) study evaluated Adhansia XR in adult patients with ADHD. Efficacy assessments were conducted at pre-dose and 1, 2, 5, 8, 11, 14, and 16 hours post-dose. The primary endpoint was the mean Permanent Product Measure of Performance Total scores (PERMP-T), averaged across all time points compared to placebo. PERMP-T, an objective, validated, skill-adjusted math test, is the combined score obtained by adding PERMP-A (number of math problems attempted) and PERMP-C (number of math problems answered correctly).
While receiving Adhansia XR, adults achieved statistically significant improvement over placebo, achieving greater mean PERMP-T scores averaged across all time points on the AWE days (post-dose score of 281.3 vs. 254.5; difference of 26.80, 95% CI [15.19, 38.41]). 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 hour 14 post-dose.
In this study, 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, viral gastroenteritis, viral infection, increased blood pressure, and hypomania.
About Adhansia XR™
Adhansia XR was developed by Purdue Pharma (Canada). The medication was granted marketing authorization from Health Canada in December 2017 and is currently marketed in Canada as FOQUEST™ for the treatment of ADHD. In the U.S., the medication was approved by the U.S. Food and Drug Administration (FDA) for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in patients six years and older in February 2019 and is currently marketed as Adhansia XR.
Adhansia XR capsules contain multilayered beads, which are composed of an immediate-release layer which contains approximately 20 percent of the methylphenidate dose, and a controlled-release layer which contains approximately 80 percent of the methylphenidate dose, for oral administration. The MLR® (multi-layer release) technology is a controlled-release delivery system patented by Purdue Pharma.
Please see Important Safety Information, including Boxed Warning, Warnings & Precautions, and Adverse Reactions below.
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.
IMPORTANT SAFETY INFORMATION1
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. Adhansia XR is also contraindicated in patients 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.
Warnings and Precautions
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.
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.
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.
Psychiatric Adverse Reactions
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.
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.
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.
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.
The most common (≥5% and twice the rate of placebo) adverse reactions occurring with Adhansia XR in adults are insomnia, dry mouth, and decreased appetite.
The most common (≥5% and twice the rate of placebo) adverse reactions occurring with Adhansia XR in pediatric patients are decreased appetite, insomnia, weight decreased, and upper abdominal pain.
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.
To report SUSPECTED ADVERSE REACTIONS, contact Purdue Pharma L.P. at 1-888-726-7535 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Prescription Medications: Risks of Addiction, Misuse, Abuse, and Diversion
For information on addiction, misuse, abuse, and diversion of prescription medications, please visit the National Institute on Drug Abuse.
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1Purdue Pharma L.P. Adhansia XR Full Prescribing Information. May 2019. Accessed June 17, 2019. Retrieved from http://app.adlontherapeutics.com/adhansia-xr/fpi.pdf.