AZSTARYS

AZSTARYS- serdexmethylphenidate chloride and dexmethylphenidate hydrochloride capsule
Corium, Inc

1 INDICATIONS AND USAGE

AZSTARYS is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older.

2 DOSAGE AND ADMINISTRATION

2.1 Pretreatment Screening

Prior to initiating treatment with AZSTARYS, 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, monitor for signs of abuse and overdose, and periodically re-evaluate the need for AZSTARYS use [see Boxed Warning, Warnings and Precautions (5.1), and Drug Abuse and Dependence (9)].

2.2 Recommended Dosage

Pediatric Patients 6 to 12 years of age

• The recommended starting dosage of AZSTARYS is 39.2 mg serdexmethylphenidate/7.8 mg dexmethylphenidate once daily in the morning.
• The dosage may be increased after one week to a dosage of 52.3 mg serdexmethylphenidate/10.4 mg dexmethylphenidate per day, or decreased after one week to a dosage of 26.1 mg serdexmethylphenidate/5.2 mg dexmethylphenidate per day, depending on response and tolerability.
• Maximum recommended dosage is 52.3 mg serdexmethylphendiate/10.4 mg dexmethyphenidate once daily.

Adults and Pediatric Patients 13 to 17 years of age

• The recommended starting dosage of AZSTARYS is 39.2 mg serdexmethylphenidate/7.8 mg dexmethylphenidate once daily in the morning.
• Increase the dosage after one week to a dosage of 52.3 mg serdexmethylphenidate/10.4 mg dexmethylphenidate per day.
• Maximum recommended dosage is 52.3 mg serdexmethylphenidate/10.4 mg dexmethylphenidate once daily.

Pharmacological treatment of ADHD may be needed for extended periods. Periodically re- evaluate the long-term use of AZSTARYS, and adjust dosage as needed.

2.3 Administration Information

Administer AZSTARYS orally once daily in the morning with or without food [see Clinical Pharmacology (12.3)].

AZSTARYS capsules may be taken whole, or opened and the entire contents sprinkled into 50 mL of water or over 2 tablespoons of applesauce. Consume all the drug/food mixture immediately or within 10 minutes of mixing; do not store for future use [see Clinical Pharmacology (12.3)].

2.4 Switching from Other Methylphenidate Products

If switching from other methylphenidate products, discontinue that treatment, and titrate with AZSTARYS using the titration schedule described above.

Do not substitute AZSTARYS for other methylphenidate products on a milligram-per-milligram basis because these products have different pharmacokinetic profiles from AZSTARYS and may have different methylphenidate base composition [see Description (11), Clinical Pharmacology (12.3)].

2.5 Dose Reduction and Discontinuation

If paradoxical aggravation of symptoms or other adverse reactions occur; the dosage should be reduced, or, if necessary, the drug should be discontinued. AZSTARYS should be periodically discontinued to assess the pediatric patient’s condition. If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.

3 DOSAGE FORMS AND STRENGTHS

AZSTARYS capsules are available as:

• 26.1 mg/5.2 mg (serdexmethylphenidate/dexmethylphenidate) – blue cap/grey body, imprinted with “286” on cap and “KP415” on the body
• 39.2 mg/7.8 mg (serdexmethylphenidate/dexmethylphenidate) – dark blue cap/grey body, imprinted with “429” on cap and “KP415” on the body
• 52.3 mg/10.4 mg (serdexmethylphenidate/dexmethylphenidate) – orange cap/grey body, imprinted with “5612” on cap and “KP415” on the body

4 CONTRAINDICATIONS

AZSTARYS is contraindicated in patients:

• with known hypersensitivity to serdexmethylphenidate, methylphenidate, or other components of AZSTARYS. Bronchospasm, rash, and pruritus have been reported in patients who received AZSTARYS. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other methylphenidate products [see Adverse Reactions (6.2)].
• receiving concomitant treatment with monoamine oxidase inhibitors (MAOIs), or within 14 days following discontinuation of treatment with an MAOI, because of the risk of hypertensive crisis [see Drug Interactions (7.1)].

5 WARNINGS AND PRECAUTIONS

5.1 Potential for Abuse and Dependence

CNS stimulants, including AZSTARYS, 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 Boxed Warning and Drug Abuse and Dependence (9.2, 9.3)].

5.2 Serious Cardiovascular Reactions

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

5.3 Blood Pressure and Heart Rate Increases

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

5.4 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 mood 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 AZSTARYS. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared to 0 in placebo-treated patients.

5.5 Priapism

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

5.6 Peripheral Vasculopathy, including Raynaud’s Phenomenon

CNS stimulants used to treat ADHD, including AZSTARYS, 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.