Cara Aldridge Young
FDA has approved Azstarys (KemPharm), the first ADHD medication to combine two medications, 70% serdexmethylphenidate (SDX) and 30% immediate-release dexmethylphenidate (d-MPH), in a once-daily capsule for treatment of ADHD in patients ages 6 years and older. Because d-MPH is fully absorbed within about 2 hours, while SDX is absorbed slowly over several hours, the drug provides both early onset of action and longer duration of therapy.
Dosing and administration
Azstarys will be available in three once-daily dosage strengths of SDX/d-MPH: 26.1/5.2 mg, 39.2/7.8 mg, and 52.3/10.4 mg.
In children ages 6 to 12 years, the recommended starting dosage is 39.2 mg/7.8 mg orally once daily in the morning, with or without food. The dosage may be increased to the maximum recommended dose of 52.3 mg/10.4 mg daily or decreased to 26.1 mg/5.2 mg daily after 1 week.
For adults and children ages 13 to 17 years, the recommended starting dosage is 39.2 mg/7.8 mg orally once daily in the morning. The dosage is increased after 1 week to 52.3 mg/10.4 mg once daily.
Patients who cannot swallow Azstarys capsules whole can open the capsule and sprinkle the contents into 50 mL of water or onto 2 tablespoons of applesauce and consume the mixture within 10 minutes of preparation.
Safety and efficacy
Azstarys’s safety and efficacy were evaluated in a multicenter, double-blind, randomized, placebo-controlled, laboratory classroom Phase III study in 150 children aged 6 to 12 years with ADHD. Compared with placebo, the medication significantly improved ADHD symptoms with a single dose, as measured by the primary endpoint: the change from baseline in SKAMP-C
rating scale scores averaged over a 13-hour laboratory classroom day. As ADHD symptoms improved, SKAMP-C
scores declined.
The Azstarys group had an average SKAMP-C score reduction of −5.4 points more than the placebo group. Adverse events that occurred more frequently in the Azstarys group (2% or more of the participants) compared with the placebo group were headache (5.4% vs. 1.3%, respectively), upper abdominal pain (4.1% vs. 1.3%), insomnia (2.7% vs. 1.3%), and sore throat (2.7% vs. 0%). No serious adverse events were reported.
Boxed warning, adverse effects
Like other CNS stimulants used to treat ADHD, Azstarys is a controlled substance that comes with a boxed warning on the high potential for abuse and dependence, particularly in patients with a personal or family history of addiction. Providers should assess patients’ risk of abuse before prescribing and monitor patients for signs of abuse and dependence while they are taking the medication.
Cardiovascular events resulting in sudden death have been reported in pediatric patients with structural cardiac abnormalities or other serious heart problems.
In adults, sudden death, stroke, and myocardial infarction have been reported. Patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmias, or coronary artery disease should not use the drug. Providers should monitor patients’ blood pressure and pulse and consider the benefits and risks in patients for whom an increase in blood pressure or heart rate would be problematic.
Because the drug has been associated with long-term suppression of growth, children’s height and weight should be monitored at appropriate intervals.
Psychotic or manic symptoms can occur in patients with no history of psychiatric illness or be exacerbated in patients with preexisting psychiatric illness. Patients should be evaluated for bipolar disorder before being prescribed the drug.
Azstarys can cause priapism—a painful erection lasting longer than 4 hours. If this happens, patients should seek medical help right away.
Common adverse effects include nausea, abdominal pain, dyspepsia, vomiting, insomnia, anxiety, affect lability, irritability, dizziness, increased blood pressure, and tachycardia.
Drug interactions
Patients taking MAOIs for depression or Parkinson’s disease should not take Azstarys at the same time or within 14 days of stopping the MAOI. The combination can cause a severe, potentially life-threatening rise in blood pressure or render blood pressure medications less effective.
In children with ADHD who are also taking risperidone, dose adjustments of either medication (or both) may raise the risk of spasms, restlessness, and other uncontrolled movements.
Patients having surgery should inform their provider of any medications they are taking, as Azstarys can interact with anesthesia drugs and cause a rapid rise in blood pressure and heart rate.
Availability
Because Azstarys contains d-MPH, a Schedule II stimulant, FDA has recommended that it also be classified as a Schedule II controlled substance. Pending a final scheduling decision by DEA, Azstarys is expected to be available this summer.