Quillivant

Dosage Forms and Strengths ( 3 ) 03/2026 Indications and Usage ( 1 ) 09/2025 Warnings and Precautions ( 5.7 ) 09/2025

1 INDICATIONS AND USAGE QUILLIVANT XR is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) [see Clinical Studies ( 14 ) ]. Limitations of Use The use of QUILLIVANT XR 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 )]. QUILLIVANT XR is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD). ( 1 ) Limitations of Use The use of QUILLIVANT XR 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 ).

2 DOSAGE AND ADMINISTRATION Before administering the dose, vigorously shake bottle for at least 10 seconds. ( 2.2 ) May be taken with or without food. ( 2.3 ) For patients 6 years and above, recommended starting dose is 20 mg given orally once daily in the morning. Dosage may be increased weekly in increments of 10 mg to 20 mg per day. Daily dosage above 60 mg is not recommended. ( 2.2 ) Reconstitution instructions for the pharmacist: Tap bottle until powder flows freely. Remove bottle cap, add specified amount of water for reconstitution. Insert bottle adapter into neck of bottle. Replace bottle cap. Shake with vigorous back and forth motion for at least 10 seconds to prepare suspension. ( 2.6 ) 2.1 Pretreatment Screening Prior to treating patients with QUILLIVANT XR, 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 QUILLIVANT XR [see Warnings and Precautions (5.10) ]. 2.2 Recommended Dosage Before administering the dose, VIGOROUSLY SHAKE the bottle of QUILLIVANT XR for at least 10 seconds, to ensure that the proper dose is administered. The recommended starting dose of QUILLIVANT XR for patients 6 years and above is 20 mg once daily in the morning. The dose may be titrated weekly in increments of 10 mg to 20 mg. Daily doses above 60 mg have not been studied and are not recommended. As with any CNS stimulant, during titration of QUILLIVANT XR, the prescribed dose should be adjusted, if necessary, until a well‐tolerated, therapeutic dose is achieved. Patients should be advised to avoid alcohol while taking QUILLIVANT XR [see Clinical Pharmacology (12.3) ]. 2.3 Administration Instructions QUILLIVANT XR should be orally administered once daily in the morning with or without food [see Clinical Pharmacology ( 12.3 ) ]. 2.4 Switching from other Methylphenidate Products If switching from other methylphenidate products, discontinue that treatment, and titrate with QUILLIVANT XR using the above titration schedule. Do not substitute for other methylphenidate products on a milligram-per-milligram basis, because of different methylphenidate base compositions and differing pharmacokinetic profiles [see Description ( 11 ) , Clinical Pharmacology ( 12.3 ) ]. 2.5 Dose Reduction and Discontinuation If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage, or, if necessary, discontinue the drug. If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued. 2.6 Reconstitution Instructions for the Pharmacist QUILLIVANT XR is supplied as a powder for oral suspension which must be reconstituted with water prior to dispensing. Preparation instructions: Tap bottle until powder flows freely. Remove bottle cap, and add specified amount of water to the bottle (see Table 1 below). Fully insert bottle adapter into neck of bottle [see Instructions for Use , Figures F and G] . Replace bottle cap. Shake with vigorous back and forth motion for at least 10 seconds to prepare suspension. Table 1: Product Reconstitution Instructions Amount of drug in bottle Amount of water to add to bottle Final reconstituted volume (yield) 300 mg 53 mL 60 mL 600 mg 105 mL 120 mL 750 mg 131 mL 150 mL 900 mg 158 mL 180 mL Store reconstituted QUILLIVANT XR at 25oC (77oF); excursions permitted from 15o to 30oC (59o to 86oF). Dispense in original packaging (bottle in carton) with bottle adapter inserted and with enclosed oral dosing dispenser. QUILLIVANT XR is stable for up to 4 months after reconstitution.

3 DOSAGE FORMS AND STRENGTHS Extended-release oral suspension (after reconstitution with water): equivalent of 25 mg of methylphenidate hydrochloride per 5 mL. Extended-release oral suspension (after reconstitution with water): equivalent of 25 mg of methylphenidate hydrochloride per 5 mL ( 3 )

4 CONTRAINDICATIONS Known hypersensitivity to methylphenidate or product components. ( 4.1 ) Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days. ( 4.2 , 7.1 ) 4.1 Hypersensitivity to Methylphenidate or other Components of QUILLIVANT XR QUILLIVANT XR is contraindicated in patients known to be hypersensitive to methylphenidate, or other components of QUILLIVANT XR. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other methylphenidate products [see Adverse Reactions ( 6.2 ) ]. 4.2 Monoamine Oxidase Inhibitors QUILLIVANT XR is contraindicated during treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with a monoamine oxidase inhibitor (MAOI), because of the risk of hypertensive crisis [see Drug Interactions ( 7.1 ) ].

6 ADVERSE REACTIONS The following are discussed in more detail in other sections of the labeling: Known hypersensitivity to methylphenidate products or other ingredients of QUILLIVANT XR [see Contraindications (4) ] Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors [see Contraindications (4) , Drug Interactions (7.1) ] Abuse, Misuse, and Addiction [see Boxed Warning , Warnings and Precautions (5.1) , Drug Abuse and Dependence (9.2 , 9.3 )] 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. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Tris Pharma, Inc. at 732-940-0358 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 Children, Adolescents, and Adults with ADHD Commonly reported (≥2% of the methylphenidate group and at least twice the rate of the placebo group) adverse reactions from placebo-controlled trials of methylphenidate products include: appetite decreased, weight decreased, nausea, abdominal pain, dyspepsia, dry mouth, vomiting, insomnia, anxiety, nervousness, restlessness, affect lability, agitation, irritability, dizziness, vertigo, tremor, blurred vision, blood pressure increased, heart rate increased, tachycardia, palpitations, hyperhidrosis, and pyrexia. Adverse Reactions in Studies with QUILLIVANT XR in Children and Adolescents with ADHD There is limited experience with QUILLIVANT XR in controlled trials. Based on this limited experience, the adverse reaction profile of QUILLIVANT XR appears similar to other methylphenidate extended-release products. The most common (≥2% in the QUILLIVANT XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 45 ADHD patients (ages 6 to 12 years) were affect lability, excoriation, initial insomnia, tic, decreased appetite, vomiting, motion sickness, eye pain, and rash. Table 2: Common Adverse Reactions occurring in ≥2% of subjects on QUILLIVANT XR and greater than placebo during the controlled cross-over phase Adverse reaction QUILLIVANT XR N= 45 Placebo N= 45 Affect lability 9% 2% Excoriation 4% 0 Initial Insomnia 2% 0 Tic 2% 0 Decreased appetite 2% 0 Vomiting 2% 0 Motion sickness 2% 0 Eye pain 2% 0 Rash 2% 0 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of methylphenidate products. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are as follows: Blood and Lymphatic System Disorders: Pancytopenia, Thrombocytopenia, Thrombocytopenic p …

7 DRUG INTERACTIONS Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed. ( 7 ) 7.1 Clinically Important Drug Interactions MAOI Inhibitors Do not administer QUILLIVANT XR concomitantly with monoamine oxidase inhibitors (MAOIs) or within 14 days after discontinuing MAOI treatment. Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Antihypertensive Drugs QUILLIVANT XR may decrease the effectiveness of drugs used to treat hypertension. Monitor blood pressure and adjust the dosage of the hypertensive drug as needed [see Warnings and Precautions (5.3) ]. Halogenated Anesthetics Concomitant use of halogenated anesthetics and QUILLIVANT XR may increase the risk of sudden blood pressure and heart rate increase during surgery. Monitor blood pressure and avoid use of QUILLIVANT XR in patients being treated with anesthetics on the day of surgery. Risperidone 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). Monitor for signs of EPS.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/othermedications/ . Risk Summary There are limited published studies and small case series that report on the use of methylphenidate in pregnant women; however, the data are insufficient to inform any drug-associated risks. There are clinical considerations [see Clinical Considerations ] . No teratogenic effects were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis at doses 2 and 11 times, respectively, the maximum recommended human dose (MRHD). However, spina bifida was observed in rabbits at a dose 40 times the MRHD [see Data ]. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal adverse reactions CNS stimulant medications, such as QUILLIVANT XR, 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. Data Animal Data In studies conducted in rats and rabbits, methylphenidate was administered orally at doses of up to 75 and 200 mg/kg/day, respectively, during the period of organogenesis. Teratogenic effects (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 40 times the maximum recommended human dose (MRHD) on a mg/m 2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (11 times the MRHD on a mg/m 2 basis). There was no evidence of specific teratogenic activity in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (7 times the MRHD on a mg/m 2 basis), which was also maternally toxic. The no effect level for embryo-fetal development in rats was 25 mg/kg/day (2 times the MRHD on a mg/m 2 basis). 8.2 Lactation Risk Summary Limited published literature reports that methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7. There are no reports of adverse effects on the breastfed infant and no effects on milk production. Long-term neurodevelopmental effects on infants from CNS stimulant exposure are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for QUILLIVANT XR and any potential adverse effects on the breastfed infant from QUILLIVANT XR or from the underlying maternal condition. Clinical Considerations Monitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain. 8.4 Pediatric Use The safety and effectiveness of QUILLIVANT XR have not been established in pediatric patients below the age of 6 years. In studies evaluating extended-release methylphenidate products, patients 4 to <6 years of age had higher systemic methylphenidate exposures than those observed in older pediatric patients at the same dosage. Pediatric patients 4 to <6 years of age also had a higher incidence of adverse reactions, including weight loss. The safety and effectiveness of QUILLIVANT XR have been established in pediatric patients ages 6 to 17 years. Use of QUILLIVANT XR in pediatric patients 6 to 12 years of age is supported by on …

12.1 Mechanism of Action Methylphenidate is a central nervous system (CNS) stimulant.

11 DESCRIPTION QUILLIVANT XR is a powder that, after reconstitution with water, forms an extended-release oral suspension formulation of methylphenidate intended for once daily oral administration. QUILLIVANT XR contains approximately 20% immediate-release and 80% extended-release methylphenidate. After reconstitution, QUILLIVANT XR contains in each 1 mL the equivalent of 5 mg of methylphenidate hydrochloride, present as methylphenidate (4.32 mg) complexed with sodium polystyrene sulfonate. Methylphenidate HCl is a central nervous system (CNS) stimulant. The chemical name is methyl α-phenyl-2-piperidineacetate hydrochloride, and its structural formula is shown in Figure 1. Figure 1: Methylphenidate structure C 14 H 19 NO 2 Mol. Wt. 233.31 QUILLIVANT XR also contains the following inactive ingredients: sodium polystyrene sulfonate, povidone, triacetin, polyvinyl acetate, sucrose, anhydrous trisodium citrate, anhydrous citric acid, sodium benzoate, sucralose, poloxamer 188, corn starch, xanthan gum, talc, banana flavor, and silicon dioxide. chem draw without HCL

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 QUILLIVANT XR 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.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied QUILLIVANT XR is supplied as powder that, after reconstitution with water, forms an extended-release oral suspension. The product is supplied in a carton. Each carton also contains one bottle, one oral dosing dispenser, and one bottle adapter. The product must be reconstituted only by the pharmacist and not by the patient or caregiver. After reconstitution, the product is a light beige to tan viscous suspension containing the equivalent of 25 mg of methylphenidate hydrochloride per 5 mL. Bottles of 300 mg (to prepare 60 mL suspension) NDC 24478-321-02 Bottles of 600 mg (to prepare 120 mL suspension) NDC 24478-322-04 Bottles of 750 mg (to prepare 150 mL suspension) NDC 24478-323-05 Bottles of 900 mg (to prepare 180 mL suspension) NDC 24478-324-06 16.2 Storage and Handling Store at 25oC (77oF); excursions permitted from 15oC to 30oC (59oF to 86oF). [See USP Controlled Room Temperature.] Dispense in original container.

16.1 How Supplied QUILLIVANT XR is supplied as powder that, after reconstitution with water, forms an extended-release oral suspension. The product is supplied in a carton. Each carton also contains one bottle, one oral dosing dispenser, and one bottle adapter. The product must be reconstituted only by the pharmacist and not by the patient or caregiver. After reconstitution, the product is a light beige to tan viscous suspension containing the equivalent of 25 mg of methylphenidate hydrochloride per 5 mL. Bottles of 300 mg (to prepare 60 mL suspension) NDC 24478-321-02 Bottles of 600 mg (to prepare 120 mL suspension) NDC 24478-322-04 Bottles of 750 mg (to prepare 150 mL suspension) NDC 24478-323-05 Bottles of 900 mg (to prepare 180 mL suspension) NDC 24478-324-06