Azstarys (serdexmethylphenidate and dexmethylphenidate)

WARNING

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.

Azstarys may cause serious side effects, including:

• Painful and prolonged erections (priapism). Priapism has happened in males who take products that contain methylphenidate. If you or your child develop priapism, get medical help right away.
• Circulation problems in fingers and toes (peripheral vasculopathy, including Raynaud's phenomenon). Signs and symptoms may include:
  • fingers or toes may feel numb, cool, or painful
  • fingers or toes may change color from pale, to blue, to red

Tell your healthcare provider if you or your child have numbness, pain, skin color change, or sensitivity to temperature in the fingers or toes.

Call your healthcare provider right away if you or your child have any signs of unexplained wounds appearing on fingers or toes during treatment with Azstarys.

• Slowing of growth (height and weight) in children. Children should have their height and weight checked often during treatment Azstarys. Azstarys treatment may be stopped if your child is not growing or gaining weight.

The most common side effects of Azstarys include:

• decreased appetite
• nausea
• indigestion
• trouble sleeping
• vomiting
• stomach pain
• weight loss
• dizziness
• mood swings
• increased blood pressure
• anxiety
• irritability
• increased heart rate

These are not all the possible side effects of Azstarys.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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).

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.

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 reevaluate the long-term use of Azstarys, and adjust dosage as needed.

Administration Information

Administer Azstarys orally once daily in the morning with or without food.

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.

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.

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.

Clinically Important Interactions With Azstarys

Table 1 presents clinically important drug interactions with Azstarys.

Table 1: Clinically Important Drug Interactions with Azstarys

Drug Abuse And Dependence

Controlled Substance

• Azstarys contains dexmethylphenidate hydrochloride, a Schedule II controlled substance, and serdexmethylphenidate. (Controlled substance schedule of serdexmethylphenidate to be determined after review by the Drug Enforcement Administration.)

Abuse

• CNS stimulants including Azstarys, 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.
• Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Both abuse and misuse may lead to addiction, and some individuals may develop addiction even when taking Azstarys as prescribed.
• 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. Individuals who abuse CNS stimulants may chew, snort, inject, or use other unapproved routes of administration which can result in overdose and death.
• To reduce the abuse of Azstarys, 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 Azstarys use.

Dependence

Physical Dependence

• Azstarys 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

• Azstarys 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.

• CNS stimulants, such as Azstarys, 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.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including Azstarys, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388.
• There are no available data on the presence of serdexmethylphenidate in human milk, effects on the breastfed infant, or effects on milk production. Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate.