Azstarys​

Azstarys (Serdexmethylphenidate and Dexmethylphenidate): Overview
Azstarys is a once-daily, extended-release stimulant medication approved by the FDA in 2021 for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in individuals aged 6 years and older. It combines two active components--serdexmethylphenidate (SDX), a prodrug of dexmethylphenidate, and dexmethylphenidate (d-MPH)—to provide both immediate and extended symptom control.

Mechanism of Action
​Azstarys works by increasing the levels of dopamine and norepinephrine in the brain. These neurotransmitters play critical roles in attention, focus, and impulse control.
  1. Dexmethylphenidate (d-MPH):
    • Provides immediate symptom relief by blocking dopamine and norepinephrine reuptake in the synaptic cleft.
  2. Serdexmethylphenidate (SDX):
    • A prodrug converted into active dexmethylphenidate in the body.
    • Provides sustained symptom control throughout the day by releasing dexmethylphenidate gradually.
This dual-release mechanism ensures a fast onset of action and long-lasting efficacy.

​Clinical Benefits
  1. Symptom Management:
    • Effective for reducing hyperactivity, impulsivity, and inattention throughout the day.
  2. Dual-Action Mechanism:
    • Combines immediate and extended-release properties for all-day symptom control.
    • Reduces the need for mid-day dosing.
  3. Improved Adherence:
    • Single-daily dosing enhances convenience and compliance.
  4. Flexibility:
    • Capsules can be swallowed whole or opened to sprinkle the contents onto food.

Dosage
Azstarys is available in capsules containing fixed doses of serdexmethylphenidate and dexmethylphenidate.
  1. Starting Dose:
    • 39.2 mg / 7.8 mg (SDX/d-MPH) taken once daily in the morning.
  2. Titration:
    • Adjust based on clinical response and tolerability.
    • Maximum dose: 52.3 mg / 10.4 mg (SDX/d-MPH) once daily.
  3. Administration Notes:
    • Can be taken with or without food.
    • Avoid dosing late in the day to minimize the risk of insomnia.
Prevalence of Side Effects
Azstarys is generally well-tolerated, but like all stimulant medications, it has potential side effects.
  1. Common Side Effects (5-20%):
    • Decreased appetite.
    • Insomnia.
    • Headache.
    • Nausea or vomiting.
    • Dry mouth.
    • Increased heart rate.
  2. Less Common Side Effects (1-5%):
    • Anxiety or restlessness.
    • Irritability.
    • Abdominal pain.
  3. Rare but Serious Side Effects (<1%):
    • Cardiovascular events: Increased blood pressure or heart rate.
    • Psychiatric symptoms: Agitation, hallucinations, or mania.
    • Growth suppression: Monitoring height and weight is recommended in children.
  4. Abuse Potential:
    • SDX reduces immediate abuse potential compared to traditional stimulants, but Azstarys still carries a Schedule II classification due to the inclusion of dexmethylphenidate.

Efficacy
​Clinical trials have shown Azstarys to:
  • Improve ADHD symptoms within 30 minutes of dosing.
  • Provide sustained symptom control for up to 13 hours.
  • Be effective across both children and adolescents.

Summary: Azstarys is a novel stimulant medication for ADHD offering dual-action symptom relief. Its combination of immediate and extended-release components ensures all-day efficacy, making it a convenient and effective option for individuals with ADHD. While generally safe, close monitoring for potential side effects and misuse is necessary.