). monitor for signs of eps.

ns and priapism have been reported with methylphenidate products. immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed. ( 5.5 ) peripheral vasculopathy, including raynaud’s phenomenon: cns stimulants used to treat adhd are associated with peripheral vasculopathy, including raynaud’s phenomenon. careful observation for digital changes is necessary during treatment with adhd stimulants. ( 5.6 ) long-term suppression of growth: monitor height and weight at appropriate intervals in pediatric patients. ( 5.7 ) 5.1 potential for abuse and dependence cns stimulants, including quillivant xr, 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 [see drug abuse and dependence ( 9.2 , 9.3 )]. 5.2 serious cardiovascular reactions stroke and myocardial infarction have occurred in adults treated with cns stimulants at recommended doses. sudden death has occurred in children and adolescents with structural cardiac abnormalities and other serious cardiac problems, and in adults taking cns stimulants at recommended doses for adhd. avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac problems. further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during treatment with quillivant xr. 5.3 blood pressure and heart rate increases cns stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mm hg) and heart rate (mean increase approximately 3 to 6 bpm). individuals may have larger increases. monitor all patients for hypertension and tachycardia. 5.4 psychiatric adverse reactions exacerbation of pre-existing psychosis cns stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder. induction of a manic episode in patients with bipolar disorder cns stimulants may induce a manic or mixed episode in patients. prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression). new psychotic or manic symptoms cns stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. if such symptoms occur, consider discontinuing quillivant xr. in a pooled analysis of multiple short-term, placebo-controlled studies of cns stimulants, psychotic or manic symptoms occurred in approximately 0.1% of cns stimulant-treated patients, compared to 0 in placebo-treated patients. 5.5 priapism prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients. priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose. priapism has also appeared during a period of drug withdrawal (drug holidays or during discontinuation). patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention. 5.6 peripheral vasculopathy, including raynaud’s phenomenon cns stimulants, including quillivant xr, used to treat adhd are associated with peripheral vasculopathy, including raynaud’s phenomenon. signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. effects of peripheral vasculopathy, including raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. signs and symptoms generally improve after reduction in dose or discontinuation of drug. careful observation of digital changes is necessary during treatment with adhd stimulants. further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. 5.7 long-term suppression of growth cns stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. careful follow-up of weight and height in pediatric patients ages 7 to 10 years who were randomized to either methylphenidate or nonmedication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and nonmedication-treated pediatric patients over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated pediatric patients (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. closely monitor growth (weight and height) in pediatric patients treated with cns stimulants, including quillivant xr. patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

nd precautions ( 5.2 )]. 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 quillivant xr use [see boxed warning , warnings and precautions ( 5.1 ), drug abuse and dependence ( 9 )]. 2.2 general dosing information 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. pharmacologic treatment of adhd may be needed for extended periods. health care providers should periodically re-evaluate the long-term use of quillivant xr, and adjust dosage as needed. 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. quillivant xr should be periodically discontinued to assess the child’s condition. 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.

e 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. clinical trials experience 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. clinical trials experience 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 purpura cardiac disorders: angina pectoris, bradycardia, extrasystole, supraventricular tachycardia, ventricular extrasystole eye disorders: diplopia, mydriasis, visual impairment general disorders: chest pain, chest discomfort, hyperpyrexia hepatobiliary disorders: severe hepatocellular injury immune system disorders: hypersensitivity reactions such as angioedema, anaphylactic reactions, auricular swelling, bullous conditions, exfoliative conditions, urticarias, pruritus nec, rashes, eruptions, and exanthemas nec investigations: alkaline phosphatase increased, bilirubin increased, hepatic enzyme increased, platelet count decreased, white blood cell count abnormal musculoskeletal, connective tissue and bone disorders: arthralgia, myalgia, muscle twitching, rhabdomyolysis nervous system disorders: convulsion, grand mal convulsion, dyskinesia, serotonin syndrome in combination with serotonergic drugs psychiatric disorders: disorientation, hallucination, hallucination auditory, hallucination visual, libido changes, mania urogenital system: priapism skin and subcutaneous tissue disorders: alopecia, erythema vascular disorders: raynaud’s phenomenon

). monitor for signs of eps.

da 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 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 one adequate and well-controlled study [see clinical studies ( 14 )]. use in 12 to 17 year old's is supported by the adequate and well-controlled studies of quillivant xr in younger pediatric patients and additional pharmacokinetic data in adolescents, along with safety information from other methylphenidate‑containing products. the long-term efficacy of methylphenidate in pediatric patients has not been established. safety and efficacy in pediatric patients below the age of 6 years have not been established. long term suppression of growth growth should be monitored during treatment with cns stimulants, including quillivant xr. children who are not growing or gaining weight as expected may need to have their treatment interrupted [see warnings and precautions ( 5.7 )]. juvenile animal data rats treated with methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. a deficit in acquisition of a specific learning task was observed in females only. the doses at which these findings were observed are at least 6 times the maximum recommended human dose (mrhd) on a mg/m 2 basis. in the study conducted in young rats, methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (postnatal day 7) and continuing through sexual maturity (postnatal week 10). when these animals were tested as adults (postnatal weeks 13 to 14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 6 times the maximum recommended human dose [mrhd] on a mg/m 2 basis) or greater, and a deficit in the acquisition of a specific learning task was observed in females exposed to the highest dose (12 times the mrhd on a mg/m 2 basis). the no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (half the mrhd on a mg/m 2 basis). the clinical significance of the long-term behavioral effects observed in rats is unknown. 8.5 geriatric use quillivant xr has not been studied in patients over the age of 65 years.

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).

le animal data rats treated with methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. a deficit in acquisition of a specific learning task was observed in females only. the doses at which these findings were observed are at least 6 times the maximum recommended human dose (mrhd) on a mg/m 2 basis. in the study conducted in young rats, methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (postnatal day 7) and continuing through sexual maturity (postnatal week 10). when these animals were tested as adults (postnatal weeks 13 to 14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 6 times the maximum recommended human dose [mrhd] on a mg/m 2 basis) or greater, and a deficit in the acquisition of a specific learning task was observed in females exposed to the highest dose (12 times the mrhd on a mg/m 2 basis). the no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (half the mrhd on a mg/m 2 basis). the clinical significance of the long-term behavioral effects observed in rats is unknown.

profiles figure 2 the single dose pharmacokinetics of d- mph under fed conditions are summarized (table 3) from studies in children and adolescents with adhd, and healthy adults following an oral dose of 60 mg quillivant xr. table 3: d-mph pk parameters (mean ±sd) after 60 mg oral dosing of quillivant xr* pk parameter children† (n=3) adolescent† (n=4) adult (n=27) t max (hr) ‡ 4.05 (3.98-6.0) 2.0 (1.98-4.0) 4.0 (1.3-7.3) t 1/2 (hr) 5.2±0.1 5.0±0.2 5.2±1.0 c max (ng/ml) 34.4±14.0 21.1±5.9 17.0±7.7 auc inf (hr*ng/ml) 378±175 178±54.2 163.2±80.3 cl (l/hr/kg) 4.27±0.70 5.06±1.42 5.66±2.15 * breakfast was given 30 min prior to drug administration † total mph measured in children (9 to 12 years old) and adolescents (13 to 15 years old), l- mph <2% of d- mph in circulation ‡ data presented as median (range) food effects in a study in adult volunteers to investigate the effects of a high-fat meal on the bioavailability of quillivant xr at a dose of 60 mg, the presence of food reduced the time to peak concentration by approximately 1 hour (fed: 4 hours vs. fasted: 5 hours). overall, a high-fat meal increased the average c max of quillivant xr by about 28% and the auc by about 19%. these changes are not considered clinically significant. elimination following a single 60 mg oral dose of quillivant xr in 28 healthy adult subjects under fasting conditions, the mean plasma terminal elimination half-life of d- methylphenidate was 5.6 (± 0.8) hours. metabolism in humans, methylphenidate is metabolized primarily via deesterification to alpha-phenyl-piperidine acetic acid (ppaa). the metabolite has little or no pharmacologic activity. excretion after oral dosing of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. the main urinary metabolite was ppaa, accounting for approximately 80% of the dose. alcohol effect an in vitro study was conducted to explore the effect of alcohol on the release characteristics of methylphenidate from quillivant xr oral suspension. at alcohol concentrations of 5% and 10%, there was no effect of alcohol on the release characteristics of methylphenidate. at 20% alcohol concentration, there was on average a 20% increase in drug exposure [see dosage and administration ( 2.2 )]. specific populations sex there is insufficient experience with the use of quillivant xr to detect gender variations in pharmacokinetics. race there is insufficient experience with the use of quillivant xr to detect ethnic variations in pharmacokinetics. age the pharmacokinetics of methylphenidate after quillivant xr administration were studied in pediatric patients with adhd between 9 and 15 years of age. after a single oral dose of 60 mg quillivant xr, plasma concentrations of methylphenidate in children (9 to 12 years old; n=3) were approximately twice the concentrations observed in adults. the plasma concentrations in adolescent patients (13 to 15 years old; n=4) were similar to those in adults. renal impairment there is no experience with the use of quillivant xr in patients with renal insufficiency. after oral administration of radiolabeled methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of ppaa. since renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of quillivant xr. hepatic impairment there is no experience with the use of quillivant xr in patients with hepatic insufficiency. figure 2

�±14.0 21.1±5.9 17.0±7.7 auc inf (hr*ng/ml) 378±175 178±54.2 163.2±80.3 cl (l/hr/kg) 4.27±0.70 5.06±1.42 5.66±2.15 * breakfast was given 30 min prior to drug administration † total mph measured in children (9 to 12 years old) and adolescents (13 to 15 years old), l- mph <2% of d- mph in circulation ‡ data presented as median (range) food effects in a study in adult volunteers to investigate the effects of a high-fat meal on the bioavailability of quillivant xr at a dose of 60 mg, the presence of food reduced the time to peak concentration by approximately 1 hour (fed: 4 hours vs. fasted: 5 hours). overall, a high-fat meal increased the average c max of quillivant xr by about 28% and the auc by about 19%. these changes are not considered clinically significant. elimination following a single 60 mg oral dose of quillivant xr in 28 healthy adult subjects under fasting conditions, the mean plasma terminal elimination half-life of d- methylphenidate was 5.6 (± 0.8) hours. metabolism in humans, methylphenidate is metabolized primarily via deesterification to alpha-phenyl-piperidine acetic acid (ppaa). the metabolite has little or no pharmacologic activity. excretion after oral dosing of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. the main urinary metabolite was ppaa, accounting for approximately 80% of the dose. alcohol effect an in vitro study was conducted to explore the effect of alcohol on the release characteristics of methylphenidate from quillivant xr oral suspension. at alcohol concentrations of 5% and 10%, there was no effect of alcohol on the release characteristics of methylphenidate. at 20% alcohol concentration, there was on average a 20% increase in drug exposure [see dosage and administration ( 2.2 )]. specific populations sex there is insufficient experience with the use of quillivant xr to detect gender variations in pharmacokinetics. race there is insufficient experience with the use of quillivant xr to detect ethnic variations in pharmacokinetics. age the pharmacokinetics of methylphenidate after quillivant xr administration were studied in pediatric patients with adhd between 9 and 15 years of age. after a single oral dose of 60 mg quillivant xr, plasma concentrations of methylphenidate in children (9 to 12 years old; n=3) were approximately twice the concentrations observed in adults. the plasma concentrations in adolescent patients (13 to 15 years old; n=4) were similar to those in adults. renal impairment there is no experience with the use of quillivant xr in patients with renal insufficiency. after oral administration of radiolabeled methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of ppaa. since renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of quillivant xr. hepatic impairment there is no experience with the use of quillivant xr in patients with hepatic insufficiency. figure 2

ation assay or in the in vitro mouse lymphoma cell forward mutation assay. sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay in cultured chinese hamster ovary (cho) cells. methylphenidate was negative in an in vivo mouse bone marrow micronucleus assay. impairment of fertility methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week continuous breeding study. the study was conducted at doses of up to 160 mg/kg/day, approximately 8-fold the maximum recommended human dose on a mg/m 2 basis.

itro mouse lymphoma cell forward mutation assay. sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay in cultured chinese hamster ovary (cho) cells. methylphenidate was negative in an in vivo mouse bone marrow micronucleus assay. impairment of fertility methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week continuous breeding study. the study was conducted at doses of up to 160 mg/kg/day, approximately 8-fold the maximum recommended human dose on a mg/m 2 basis.

classroom using the swanson, kotkin, agler, m-flynn, and pelham (skamp) rating scale. the primary efficacy endpoint was the skamp-combined score at 4 hours post-dosing. the key secondary efficacy endpoints were the skamp-combined scores at 0.75, 2, 8, 10, and 12 hours post-dosing. results from the first double-blind, placebo-controlled week of the study are summarized in figure 3. skamp-combined scores were statistically significantly lower (improved) at all time points (0.75, 2, 4, 8, 10, 12 hours) post-dosing with quillivant xr compared to placebo. figure 3: absolute skamp-combined score after treatment with quillivant xr or placebo during period 1. figure 3 figure 3

nse in original container. disposal comply with local laws and regulations on drug disposal of cns stimulants. dispose of remaining, unused, or expired quillivant xr by a medicine take-back program or by an authorized collector registered with the drug enforcement administration. if no take‑back program or authorized collector is available, mix quillivant xr with an undesirable, nontoxic substance to make it less appealing to children and pets. place the mixture in a container such as a sealed plastic bag and discard quillivant xr in the household trash.

his medicine in its original packaging (bottle within carton) with the bottle adapter fully inserted and the accompanying oral dosing dispenser. use only with the oral dosing dispenser provided with this product. check and make sure that the quillivant xr bottle contains liquid medicine. if quillivant xr is in powder form, do not use it. return it to your pharmacist. vigorously shake the bottle of quillivant xr for at least 10 seconds before each dose, to ensure that the proper dose is administered. remove the bottle cap. confirm that the bottle adapter has been inserted into top of the bottle. insert the tip of the oral dosing dispenser provided with this product into the bottle adapter. turn bottle upside down and withdraw prescribed amount of quillivant xr into the oral dosing dispenser. remove filled oral dosing dispenser from bottle and dispense quillivant xr directly into mouth. replace bottle cap and store bottle as directed. wash oral dosing dispenser after each use (components are dishwasher-safe). serious cardiovascular risks advise patients, caregivers, and family members that there is a potential for serious cardiovascular risks including sudden death, myocardial infarction, and stroke with quillivant xr use. instruct patients to contact a health care provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease [see warnings and precautions ( 5.2 )]. blood pressure and heart rate increases advise patients that quillivant xr can elevate blood pressure and heart rate [see warnings and precautions ( 5.3 )]. psychiatric risks advise patients that quillivant xr, at recommended doses, can cause psychotic or manic symptoms, even in patients without a prior history of psychotic symptoms or mania [see warnings and precautions ( 5.4 )]. priapism advise patients, caregivers, and family members of the possibility of painful or prolonged penile erections (priapism). instruct the patient to seek immediate medical attention in the event of priapism [see warnings and precautions ( 5.5 )]. circulation problems in fingers and toes [peripheral vasculopathy, including raynaud’s phenomenon] instruct patients beginning treatment with quillivant xr about the risk of peripheral vasculopathy, including raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red. instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking quillivant xr. further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. suppression of growth advise patients, families, and caregivers that quillivant xr can cause slowing of growth and weight loss [see warnings and precautions ( 5.7 )]. alcohol effect patients should be advised to avoid alcohol while taking quillivant xr oral suspension. consumption of alcohol while taking quillivant xr may result in a more rapid release of the dose of methylphenidate [see clinical pharmacology ( 12.3 )]. this product’s label may have been updated. for current full prescribing information, please visit www.trispharma.com . distributed by: manufactured by: tris pharma, inc. monmouth junction, nj 08852 lb8529 rev. 01 06/2021 next wave 30%

4 (continued). if bottle adapter (see figure e) has not been inserted by the pharmacist into the bottle, insert adapter into the bottle as shown (see figure e and figure f). after the bottle adapter has been fully inserted into the bottle (see figure g) , it should not be removed. if the bottle adapter has not been inserted and is missing from the box, contact your pharmacist. the bottle adapter must be fully inserted and should be even with the mouth of the bottle and must remain in place to allow the child resistant cap to work the right way. step 5. check the quillivant xr dose in milliliters (ml) as prescribed by your health care provider. locate this number on the oral dosing dispenser (see figure h). step 6. insert tip of the oral dosing dispenser into the upright bottle and push the plunger all the way down (see figure i). step 7. with the oral dosing dispenser in place, turn the bottle upside down. pull the plunger to the number of ml you need (the amount of liquid medicine in step 5 – see figure j ). step 7 (continued). measure the number of ml of medicine from the white end of the plunger (see figure k). step 8. remove the oral dosing dispenser from the bottle adapter. step 9. slowly squirt quillivant xr directly into your or your child’s mouth (see figure l). step 10. cap the bottle tightly. store the bottle upright at 59°f to 86°f (15°c to 30°c) (see figure m). figure m step 11. clean the oral dosing dispenser after each use by placing in the dishwasher, or by rinsing with tap water (see figure n). figure n these instructions for use have been approved by the u..s. food and drug administration. this product’s label may have been updated. for current full prescribing information, please visit www.trispharma.com . distributed by: manufactured by: tris pharma, inc. monmouth junction, nj 08852 lb8529 rev. 01 06/2021 figure a figure b figure c figure d figure e and figure g figure g figure h figure i figure j figure k figure l figure m figure n next wave 30%