Serdexmethylphenidate And Dexmethylphenidate
FDA Drug Information • Also known as: Azstarys
- Brand Names
- Azstarys
- Route
- ORAL
- Dosage Form
- CAPSULE
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: ABUSE, MISUSE, AND ADDICTION AZSTARYS has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including AZSTARYS, can result in overdose and death [see Overdosage ( 10 )], and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection. Before prescribing AZSTARYS, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout AZSTARYS treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction [see Warnings and Precautions ( 5.1 ) and Drug Abuse and Dependence ( 9.2 )]. WARNING: ABUSE, MISUSE, AND ADDICTION See full prescribing information for complete boxed warning. AZSTARYS has a high potential for abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Misuse and abuse of CNS stimulants, including AZSTARYS, can result in overdose and death ( 5.1 , 9.2 , 10 ): Before prescribing AZSTARYS, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks, proper storage of the drug, and proper disposal of any unused drug. Throughout treatment, reassess each patient’s risk and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
Description
11 DESCRIPTION AZSTARYS (serdexmethylphenidate and dexmethylphenidate) capsules contain dexmethylphenidate, a CNS stimulant, and serdexmethylphenidate, a prodrug of dexmethylphenidate. AZSTARYS capsules are intended for oral administration and each capsule contains a fixed molar ratio of 30% dexmethylphenidate and 70% serdexmethylphenidate. AZSTARYS contains 26.1/5.2, 39.2/7.8, or 52.3/10.4 mg of serdexmethylphenidate/ dexmethylphenidate (equivalent to 28/6, 42/9, or 56/12 mg of serdexmethylphenidate chloride/ dexmethylphenidate hydrochloride, respectively. The combined molar dose of serdexmethylphenidate and dexmethylphenidate in each dosage strength of AZSTARYS is equivalent to 20, 30, or 40 mg dexmethylphenidate hydrochloride, respectively (equivalent to 17.3, 25.9 or 34.6 mg dexmethylphenidate free base, respectively). The chemical name of serdexmethylphenidate chloride is 3-((( 1S )-1-carboxy-2-hydroxyethyl)carbamoyl)-1-(((( 2R )-2-(2-( 1R )-methoxy-2-oxo-1-phenylethyl)piperidine-1-carbonyl)oxy)methyl)pyridinium chloride. Its molecular formula is C 25 H 30 N 3 O 8 +
What Is Serdexmethylphenidate And Dexmethylphenidate Used For?
1 INDICATIONS AND USAGE AZSTARYS is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older. Limitations of Use The use of AZSTARYS is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage [see Warnings and Precautions ( 5.7 ), Use in Specific Populations ( 8.4 )]. AZSTARYS is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older. ( 1 ) Limitations of Use The use of AZSTARYS is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage (5.7, 8.4).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Pediatric Patients 6 to 12 years : Recommended starting dosage is 39.2 mg/7.8 mg orally once daily in the morning. Dosage may be increased to 52.3 mg/10.4 mg daily or decreased to 26.1 mg/5.2 mg daily after one week. Maximum recommended dosage is 52.3 mg/10.4 mg once daily. ( 2.2 ) Adults and Pediatric Patients 13 to 17 years: Recommended starting dosage is 39.2 mg/7.8 mg orally once daily in the morning. Increase the dosage after one week to 52.3 mg/10.4 mg once daily depending on response and tolerability. ( 2.2 ) Administer with or without food. ( 2.3 ) Swallow capsules whole or open and sprinkle onto applesauce or add to water. ( 2.3 ) To avoid substitution errors and overdosage, do not substitute for other methylphenidate products on a milligram-per-milligram basis. ( 2.4 ) 2.1 Pretreatment Screening Prior to treating patients 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 )]. the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating AZSTARYS [see Warnings and Precautions ( 5.10 )]. 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, depending on response and tolerability. Maximum recommended dosage is 52.3 mg serdexmethylphenidate/10.4 mg dexmethylphenidate once daily. 2.3 Administration Instructions 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...
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions (5.1) , and Drug Abuse and Dependence (9.2 , 9.3) ] Known hypersensitivity to methylphenidate or other ingredients of AZSTARYS [see Contraindications (4) ] Hypertensive Crisis with Concomitant Use of Monoamine Oxidase Inhibitors [see Contraindications (4) ] Risks to Patients with Serious Cardiac Disease [see Warnings and Precautions (5.2) ] Increased Blood Pressure and Heart Rate [see Warnings and Precautions (5.3) ] Psychiatric Adverse Reactions [see Warnings and Precautions (5.4) ] Priapism [see Warnings and Precautions (5.5) ] Peripheral Vasculopathy, including Raynaud's Phenomenon [see Warnings and Precautions (5.6) ] Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions (5.7) ] Acute Angle Closure Glaucoma [see Warnings and Precautions (5.8) ] Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions (5.9) ] Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions (5.10) ] Based on accumulated data from other methylphenidate products, the most common (>5% and twice the rate of placebo) adverse reactions are appetite decreased, insomnia, nausea, vomiting, dyspepsia, abdominal pain, weight decreased, anxiety, dizziness, irritability, affect lability, tachycardia, and blood pressure increased. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Corium, LLC at 1-855-253-2407 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in Studies with Other Methylphenidate Products in Pediatric Patients and Adults with ADHD Commonly reported (≥ 5% of the methylphenidate group and at least twice the rate of the placebo group) adverse reactions from placebo-controlled trials of methylphenidate products include: decreased appetite, decreased weight, nausea, abdominal pain, dyspepsia, vomiting, insomnia, anxiety, affect lability, irritability, dizziness, increased blood pressure, and tachycardia. Adverse Reactions in Studies with AZSTARYS in Pediatric Patients (6 to 12 years) with ADHD Short-Term Study A short-term study conducted in pediatric patients 6 to 12 years of age with ADHD was comprised of a 3-week, open-label, dose optimization phase in which all patients received AZSTARYS (n=155), followed by a 1-week, double-blind, controlled phase in which patients were randomized to continue AZSTARYS (n=74) or switch to placebo (n=76). Because of the study design, the reported adverse reaction rates cannot be used to predict the rates that may be expected in clinical practice. Long-Term Study A long-term, open-label safety study was conducted in pediatric patients 6 to 12 years of age with ADHD who either completed the short-term study or were de novo patients. This study was comprised of a 3-week dose optimization phase for patients not recently treated with AZSTARYS followed by a 12-month treatment phase for all patients during which 238 patients received open- label AZSTARYS and had evaluable safety data. A total of 154 patients were treated for 12 months. Because of the open-label, uncontrolled design of this study, the reported adverse reaction rates cannot be assessed in terms of a causal relationship to AZSTARYS treatment. To adjust for normal growth, z-scores were derived (measured in standard deviations [SD]); z- scores normalize for the natural growth of children and adolescents by comparisons to age- and sex-matched population standards. A z-score change less than 0.5 SD is considered not clinically significant. In this study, the mean increase in weight from baseline...
Drug Interactions
7 DRUG INTERACTIONS Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed. ( 7.1 ) 7.1 Clinically Important Interactions with AZSTARYS Table 1 presents clinically important drug interactions with AZSTARYS. Table 1: Clinically Important Drug Interactions with AZSTARYS Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact Concomitant use of MAOIs and CNS stimulants, including AZSTARYS, can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see Contraindications ( 4 )] . Intervention Do not administer AZSTARYS concomitantly with MAOIs or within 14 days after discontinuing MAOI treatment [see Contraindications ( 4 )] Antihypertensive Drugs Clinical Impact AZSTARYS may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions ( 5.3 )] . Intervention Monitor blood pressure and adjust the dosage of the antihypertensive drug, as needed. Halogenated Anesthetics Clinical Impact Concomitant use of halogenated anesthetics and AZSTARYS may increase the risk of sudden blood pressure and heart rate increase during surgery. Intervention Avoid use of AZSTARYS in patients being treated with anesthetics on the day of surgery. Risperidone Clinical Impact Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS). Intervention Monitor for signs of EPS.
Contraindications
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 )] . Known hypersensitivity to serdexmethylphenidate, methylphenidate, or product components. ( 4 ) Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days. ( 4 )
Pregnancy and Breastfeeding
8.1 Pregnancy Pregnancy Exposure Registry 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. Risk Summary There are no available data on AZSTARYS use in pregnant women to evaluate for a drug- associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes; however, AZSTARYS contains dexmethylphenidate and serdexmethylphenidate, a prodrug of dexmethylphenidate. Dexmethylphenidate is the d-threo enantiomer of racemic methylphenidate. Published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There may be risks to the fetus associated with the use of CNS stimulants use during pregnancy ( see Clinical Considerations ). Embryo-fetal development studies in rats showed delayed fetal skeletal ossification at doses up to 3 times the maximum recommended human dose (MRHD) of 40 mg/day dexmethylphenidate hydrochloride given to adults based on plasma levels. A decrease in pup weight in males was observed in a pre- and post-natal development study with oral administration of dexmethylphenidate to rats throughout pregnancy and lactation at doses 3 times the MRHD of 40 mg/day dexmethylphenidate hydrochloride given to adults based on plasma levels ( see Data ). No evidence of developmental effects were found in an embryo-fetal development study with oral administration of serdexmethylphenidate to rabbits during organogenesis at doses up to approximately 49 times the MRHD of 52 mg/day serdexmethylphenidate given to adults based on plasma levels ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All...
Overdosage
10 OVERDOSAGE Clinical Effects of Overdose Overdose of CNS stimulants is characterized by the following sympathomimetic effects: Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop. CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur. Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop. Overdose Management Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of AZSTARYS should be considered when treating patients with overdose. Because methylphenidate has a large volume of distribution and is rapidly metabolized, dialysis is not useful. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING AZSTARYS (serdexmethylphenidate/dexmethylphenidate) capsules are available as follows: 26.1 mg/5.2 mg Capsules – blue cap/grey body, imprinted with "286" on cap and "KP415" on the body Bottles of 100 ................................................................... NDC 65038-0286-99 39.2 mg/7.8 mg Capsules – dark blue cap/grey body, imprinted with "429" on cap and "KP415" on the body Bottles of 100 ................................................................... NDC 65038-0429-99 52.3 mg/10.4 mg Capsules – orange cap/grey body, imprinted with "5612" on cap and "KP415" on the body Bottles of 100 ................................................................... NDC 65038-0561-99 Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. Protect from moisture. Dispense in tight container (USP).
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.