Daytrana
methylphenidate · Patch · Transdermal
Uses
(methylphenidate transdermal system) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 17 years of age. Limitations of Use The use of DAYTRANA 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 ( 5.8 ), Use in Specific Populations ( 8.4 )] . DAYTRANA is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 17 years of age. ( 1 ) Limitations of Use The use of DAYTRANA 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 ( 5.8 , 8.4 ).
Dosage and administration
The recommended starting dose for patients new to or converting from another formulation of methylphenidate is 10 mg. ( 2.2 ) DAYTRANA should be applied to the hip area (using alternating sites) 2 hours before an effect is needed and should be removed 9 hours after application. DAYTRANA may be removed earlier than 9 hours if a shorter duration of effect is desired or late day side effects appear. ( 2.2 , 2.3 ) Dosage should be titrated to effect. Dose titration, final dosage, and wear time should be individualized according to the needs and response of the patient. ( 2.2 ) 2.1 Pretreatment Screening Prior to treating patients with DAYTRANA, 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 DAYTRANA [see Warnings and Precautions ( 5.15 )] . 2.2 Recommended Dosage It is recommended that DAYTRANA be applied to the hip area 2 hours before an effect is needed and should be removed 9 hours after application. Dosage should be titrated to effect. The recommended dose titration schedule is shown in the table below. Dose titration, final dosage, and wear time should be individualized according to the needs and response of the patient. *Nominal in vivo delivery rate in children and adolescents when applied to the hip, based on a 9-hour wear period. Table 1 DAYTRANA - Recommended Titration Schedule (Patients New to Methylphenidate) Upward Titration, if Response is Not Maximized Week 1 Week 2 Week 3 Week 4 Transdermal System Size 12.5 cm 2 18.75 cm 2 25 cm 2 37.5 cm 2 Nominal Delivered Dose* (mg/9 hours) 10 mg 15 mg 20 mg 30 mg Delivery Rate* (1.1 mg/hr)* (1.6 mg/hr)* (2.2 mg/hr)* (3.3 mg/hr)* Patients converting from another formulation of methylphenidate should follow the above titration schedule due to differences in bioavailability of DAYTRANA compared to other products. 2.3 Application The parent or caregiver should be encouraged to use the administration chart included with each carton of DAYTRANA to monitor application and removal time, and method of disposal. It is recommended that parents or caregivers apply and remove the transdermal system for children; responsible adolescents may apply or remove the transdermal system themselves if appropriate. If a transdermal system was removed without the parent or caregiver's knowledge, or if a transdermal system is missing from the tray, the parent or caregiver should be encouraged to ask the child when and how the transdermal system was removed. The Medication Guide includes a timetable to calculate when to remove DAYTRANA, based on the 9-hour application time. The adhesive side of DAYTRANA should be placed on a clean, dry area of the hip. The area selected should not be oily, damaged, or irritated. Apply DAYTRANA to the hip area avoiding the waistline, since clothing may cause the transdermal system to rub off. When applying the transdermal system the next morning, place on the opposite hip at a new site if possible. If patients or caregivers experience difficulty separating the transdermal system from the release liner or observe transfer of adhesive to the liner, tearing and/or other damage to the transdermal system during removal from the liner, the transdermal system should be discarded and a new transdermal system should be applied. Patients or caregivers should inspect the release liner to ensure that no adhesive containing medication has transferred to the liner. If adhesive transfer has occurred, the transdermal system should be discarded. Refer to the Instructions for Use for recommendations for discarding used DAYTRANA. DAYTRANA should be applied immediately after opening the individual pouch and removing the protective liner. Do not use if the individual pouch seal is broken or if the transdermal system appears to be damaged. Do not cut transdermal systems. Only intact transdermal systems should be applied. The transdermal system should then be pressed firmly in place with the palm of the hand for approximately 30 seconds, making sure that there is good contact of the transdermal system with the skin, especially around the edges. Exposure to water during bathing, swimming, or showering can affect transdermal system adherence. DAYTRANA should not be applied or re-applied with dressings, tape, or other common adhesives. In the event that a transdermal system does not fully adhere to the skin upon application, or becomes partially or fully detached during wear time, the transdermal system should be discarded and a new transdermal system may be applied at a different site. The total recommended wear time for that day should remain 9 hours regardless of the number of transdermal systems used. All patients should be advised to avoid exposing the DAYTRANA application site to direct external heat sources, such as hair dryers, heating pads, electric blankets, heated water beds, etc., while wearing the transdermal system [see Warnings and Precautions ( 5.10 )] . When heat is applied to DAYTRANA after transdermal system application, both the rate and the extent of absorption are significantly increased. The temperature-dependent increase in methylphenidate absorption can be greater than 2-fold [see Clinical Pharmacology ( 12.3 )] . This increased absorption can be clinically significant and result in overdose of methylphenidate [see Overdosage ( 10 )] . DAYTRANA should not be stored in refrigerators or freezers. 2.4 Removal of DAYTRANA DAYTRANA should be peeled off slowly. If necessary, transdermal system removal may be facilitated by gently applying an oil-based product (i.e., petroleum jelly, olive oil, or mineral oil) to the transdermal system edges, gently working the oil underneath the transdermal system edges.
Dosage forms and strengths
Four dosage strengths are available: *Nominal in vivo delivery rate in children and adolescents when applied to the hip, based on a 9-hour wear period. Nominal Dose Delivered (mg) Over 9 Hours* Dosage Rate* (mg/hr) Transdermal System Size (cm 2 ) Methylphenidate Content per Transdermal System (mg) 10 1.1 12.5 27.5 15 1.6 18.75 41.3 20 2.2 25 55 30 3.3 37.5 82.5 Transdermal system: 10mg/9 hours (1.1 mg/hr), 15mg/9 hours (1.6 mg/hr), 20mg/9 hours (2.2 mg/hr), 30mg/9 hours (3.3 mg/hr) ( 3 )
Contraindications
Known hypersensitivity to methylphenidate ( 4.1 ) Patients currently using or within 2 weeks of using an MAO inhibitor ( 4.2 ) 4.1 Hypersensitivity to Methylphenidate DAYTRANA is contraindicated in patients known to be hypersensitive to methylphenidate or other components of the product (polyester/ethylene vinyl acetate laminate film backing, acrylic adhesive, silicone adhesive, and fluoropolymer-coated polyester) [see Description ( 11 )] . 4.2 Monoamine Oxidase Inhibitors DAYTRANA is contraindicated during treatment with monoamine oxidase inhibitors, and within a minimum of 14 days following discontinuation of treatment with a monoamine oxidase inhibitor (hypertensive crises may result).
Warnings and precautions
Risks to Patients with Serious Cardiac Disease: Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease. ( 5.2 ) Increased Blood Pressure and Heart Rate: Monitor blood pressure and pulse. ( 5.3 ) Psychiatric Adverse Reactions: Prior to initiating DAYTRANA, screen patients for risk factors for developing a manic episode. If new psychotic or manic symptoms occur, consider discontinuing DAYTRANA. ( 5.4 ) Seizures: Stimulants may lower the convulsive threshold. Discontinue in the presence of seizures. ( 5.5 ) Priapism: If abnormally sustained or frequent and painful erections occur, patients should seek immediate medical attention. ( 5.6 ) Peripheral Vasculopathy, including Raynaud’s phenomenon: Careful observation for digital changes is necessary during DAYTRANA treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy. ( 5.7 ) Long-Term Suppression of Growth in Pediatric Patients: Closely monitor (height and weight) in pediatric patients. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted. ( 5.8 ) Chemical Leukoderma: DAYTRANA use may result in a persistent loss of skin pigmentation at and around the application site. Loss of pigmentation, in some cases, has been reported at other sites distant from the application site. Monitor for signs of skin depigmentation. Discontinue DAYTRANA if it occurs. ( 5.9 ) Contact Sensitization: Use of DAYTRANA may lead to contact sensitization. Treatment should be discontinued if contact sensitization is suspected. Erythema is commonly seen with use of DAYTRANA and is not by itself an indication of sensitization. However, contact sensitization should be suspected if erythema is accompanied by evidence of a more intense local reaction (edema, papules, vesicles) that does not significantly improve within 48 hours or spreads beyond the transdermal system site. ( 5.10 ) External Heat: Patients should be advised to avoid exposing the DAYTRANA application site to direct external heat sources. When heat is applied to DAYTRANA after application, both the rate and extent of absorption are significantly increased. ( 5.11 ) Hematologic monitoring: Periodic CBC, differential, and platelet counts are advised during prolonged therapy. ( 5.12 ) Acute Angle Closure Glaucoma: DAYTRANA-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist. ( 5.13 ) Increased Intraocular Pressure (IOP) and Glaucoma: Prescribe DAYTRANA to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor patients with a history of increased IOP or open angle glaucoma. ( 5.14 ) Motor and Verbal Tics and Worsening of Tourette’s Syndrome: Before initiating DAYTRANA, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome. Discontinue treatment if clinically appropriate. ( 5.15 ) 5.1 Abuse, Misuse, and Addiction DAYTRANA has a high potential for abuse and misuse. The use of DAYTRANA exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. DAYTRANA can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence ( 9.2 )] . Misuse and abuse of CNS stimulants, including DAYTRANA, 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 DAYTRANA, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their caregivers or families about these risks. Advise patients to store DAYTRANA in a safe place, preferably locked, and instruct patients to not give DAYTRANA to anyone else. Throughout DAYTRANA treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction. DAYTRANA has special disposal instructions. Instruct patients to find a take back location to dispose of unused or expired DAYTRANA. If a take back program is unavailable, instruct them to: Remove DAYTRANA from its pouch, separate it from its liner, fold it in half with the adhesive sides touching each other, and immediately flush the used transdermal system down the toilet, and Place the pouch and liner in a container, close the container, and throw out the container in the trash (advise patients not to flush the pouch and liner down the toilet). 5.2 Risks to Patients with Serious Cardiac Disease Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage. Avoid DAYTRANA use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 5.3 Increased Blood Pressure and Heart Rate CNS stimulants may cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm). Some patients may have larger increases. Monitor all DAYTRANA-treated 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 Disease CNS stimulants may induce a manic or mixed episode in patients.
Side effects
Detailed information on serious and adverse reactions of particular importance is provided in the Boxed Warning and Warnings and Precautions ( 5 ) sections: Abuse, Misuse, and Addiction [see Boxed Warning ] Hypersensitivity to Methylphenidate [ see Contraindications ( 4.1 ) ] Monoamine Oxidase Inhibitors [ see Contraindications ( 4.2 ) and Drug Interactions ( 7.1 ) ] 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 )] Seizures [see Warnings and Precautions ( 5.5 )] Priapism [see Warnings and Precautions ( 5.6 )] Peripheral Vasculopathy [see Warnings and Precautions ( 5.7 )] Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions ( 5.8 )] Chemical Leukoderma [see Warnings and Precautions ( 5.9 )] Contact Sensitization [see Warnings and Precautions ( 5.10 )] External Heat [see Warnings and Precautions ( 5.11 )] Hematologic Monitoring [see Warnings and Precautions ( 5.12 )] Acute Angle Closure Glaucoma [see Warnings and Precautions ( 5.13 )] Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions ( 5.14 )] Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions ( 5.15 )] Pediatric patients (ages 6 to 12 years): The most commonly (≥5% and twice the rate of placebo) reported adverse reactions in pediatric patients ages 6 to 12 years included appetite decreased, insomnia, nausea, vomiting, weight decreased, tic, affect lability, and anorexia. ( 6.1 ) Pediatric patients (ages 13 to 17 years): The most commonly (≥5% and twice the rate of placebo) reported adverse reactions in pediatric patients ages 13 to 17 years included appetite decreased, nausea, insomnia, weight decreased, dizziness, abdominal pain, and anorexia. The majority of subjects in these trials had erythema at the application site. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Noven Therapeutics, LLC at 1-800-455-8070 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 reactions 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 practice. The most commonly reported (frequency ≥ 5% and twice the rate of placebo) adverse reactions in a controlled trial in children aged 6-12 included appetite decreased, insomnia, nausea, vomiting, weight decreased, tic, affect lability, and anorexia. The most commonly reported (frequency ≥ 5% and twice the rate of placebo) adverse reactions in a controlled trial in adolescents aged 13-17 were appetite decreased, nausea, insomnia, weight decreased, dizziness, abdominal pain, and anorexia [see Adverse Reactions ( 6.1 )] . The most common (≥ 2% of subjects) adverse reaction associated with discontinuations in double-blind clinical trials in children or adolescents was application site reactions [see Adverse Reactions ( 6.1 )] . The overall DAYTRANA development program included exposure to DAYTRANA in a total of 2,152 participants in clinical trials, including 1,529 children aged 6-12, 223 adolescents aged 13-17, and 400 adults. The 1,752 child and adolescent subjects aged 6-17 years were evaluated in 10 controlled clinical studies, 7 open-label clinical studies, and 5 clinical pharmacology studies. In a combined studies pool of children using DAYTRANA with a wear time of 9 hours, 212 subjects were exposed for ≥ 6 months and 115 were exposed for ≥ 1 year; 85 adolescents were exposed for ≥ 6 months. Most patients studied were exposed to DAYTRANA transdermal system sizes of 12.5 cm 2 , 18.75 cm 2 , 25 cm 2 or 37.5 cm 2 , with a wear time of 9 hours. In the data presented below, the adverse reactions reported during exposure were obtained primarily by general inquiry at each visit, and were recorded by the clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of events into a smaller number of standardized event categories. Adverse Reactions in Clinical Studies with Discontinuation of Treatment In a 7-week double-blind, parallel-group, placebo-controlled study in children with ADHD conducted in the outpatient setting, 7.1% (7/98) of patients treated with DAYTRANA discontinued due to adverse events compared with 1.2% (1/85) receiving placebo. The most commonly reported (≥ 1% and twice the rate of placebo) adverse reactions leading to discontinuation in the DAYTRANA group were application site reaction (2%), tics (1%), headache (1%), and irritability (1%). In a 7-week double-blind, parallel-group, placebo-controlled study in adolescents with ADHD conducted in the outpatient setting, 5.5% (8/145) of patients treated with DAYTRANA discontinued due to adverse reactions compared with 2.8% (2/72) receiving placebo. The most commonly reported adverse reactions leading to discontinuation in the DAYTRANA group were application site reaction (2%) and decreased appetite/anorexia (1.4%). Commonly Observed Adverse Reactions in Double-Blind, Placebo-Controlled Trials Skin Irritation and Application Site Reactions DAYTRANA is a dermal irritant. In addition to the most commonly reported adverse reactions presented in Table 2, the majority of subjects in those studies had minimal to definite skin erythema at the DAYTRANA application site. This erythema generally caused no or minimal discomfort and did not usually interfere with therapy or result in discontinuation from treatment. Erythema is not by itself a manifestation of contact sensitization.
Drug interactions
Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed. ( 7.2 ) 7.1 Monoamine Oxidase Inhibitors (MAOI) Concomitant use of MAOIs and CNS stimulants, including DAYTRANA, can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see Contraindications ( 4.2 )] . Concomitant use of DAYTRANA with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated. 7.2 Antihypertensive Drugs DAYTRANA may decrease the effectiveness of drugs used to treat hypertension. Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed [see Warnings and Precautions ( 5.2 )] . 7.3 Coumarin Anticoagulants, Antidepressants, and Selective Serotonin Reuptake Inhibitors Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and some tricyclic drugs (e.g., imipramine, clomipramine, desipramine) and selective serotonin reuptake inhibitors. Downward dose adjustments of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentrations (or, in the case of coumarin, coagulation times), when initiating or discontinuing methylphenidate. 7.4 Halogenated Anesthetics Concomitant use of halogenated anesthetics and methylphenidate may increase the risk of sudden blood pressure and heart rate increase during surgery. Avoid use of DAYTRANA in patients being treated with anesthetics on the day of surgery. 7.5 Risperidone Combined use of methylphenidate with risperidone when there is a change in dosage, whether an increase or decrease, of either or both medications, may increase the risk of extrapyramidal symptoms (EPS). Monitor for signs of EPS.
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, including DAYTRANA, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visit https://womensmentalhealth.org/adhd-medications/ . Risk Summary Published studies and post-marketing reports on methylphenidate use during pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the fetus associated with the use of CNS stimulants during pregnancy ( see Clinical Considerations ) . No effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis. However, spina bifida was observed in rabbits when given oral doses of 200 mg/kg/day. When methylphenidate was administered orally to rats throughout pregnancy and lactation, offspring growth and survival were decreased at maternally toxic doses (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinical recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal adverse reactions CNS stimulants, such as DAYTRANA, 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 Animal reproduction toxicity studies with transdermal methylphenidate have not been performed. In embryo-fetal development studies conducted in rats and rabbits, methylphenidate was administered orally to pregnant animals during the period of organogenesis, at doses up to 100 and 200 mg/kg/day, respectively. No evidence of morphological development effects was found in either of the species; however, increased incidences of fetal skeletal variations were observed in rats at 60 mg/kg or greater and an increase in fetal visceral variations was seen in rabbits at the highest dose. In a previous study, methylphenidate was shown to have malformations (increased incidence of fetal spina bifida) in rabbits when given oral doses of 200 mg/kg/day. When methylphenidate was administered orally to rats throughout pregnancy and lactation at doses of up to 60 mg/kg/day, offspring growth and survival were decreased at maternally toxic doses. In a study in which oral methylphenidate was given to rats throughout pregnancy and lactation at doses up to 60 mg/kg/day, offspring weights and survival were decreased at 40 mg/kg/day and above; these doses caused some maternal toxicity. 8.2 Lactation Risk Summary Limited published literature, based on breast milk sampling from five mothers, 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 stimulant exposure are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for DAYTRANA and any potential adverse effects on the breastfed infant from DAYTRANA 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 DAYTRANA 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 DAYTRANA for the treatment of ADHD have been established in pediatric patients 6 to 17 years. Long Term Suppression of Growth Growth should be monitored during treatment with stimulants, including DAYTRANA. Children who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions ( 5.8 )] . Juvenile Animal Toxicity 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. Studies with transdermal methylphenidate have not been performed in juvenile animals. In a 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 13-14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose. The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day. The clinical significance of the long-term behavioral effects observed in rats is unknown.
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including DAYTRANA, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visit https://womensmentalhealth.org/adhd-medications/ . Risk Summary Published studies and post-marketing reports on methylphenidate use during pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There are risks to the fetus associated with the use of CNS stimulants during pregnancy ( see Clinical Considerations ) . No effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis. However, spina bifida was observed in rabbits when given oral doses of 200 mg/kg/day. When methylphenidate was administered orally to rats throughout pregnancy and lactation, offspring growth and survival were decreased at maternally toxic doses (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinical recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal adverse reactions CNS stimulants, such as DAYTRANA, 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 Animal reproduction toxicity studies with transdermal methylphenidate have not been performed. In embryo-fetal development studies conducted in rats and rabbits, methylphenidate was administered orally to pregnant animals during the period of organogenesis, at doses up to 100 and 200 mg/kg/day, respectively. No evidence of morphological development effects was found in either of the species; however, increased incidences of fetal skeletal variations were observed in rats at 60 mg/kg or greater and an increase in fetal visceral variations was seen in rabbits at the highest dose. In a previous study, methylphenidate was shown to have malformations (increased incidence of fetal spina bifida) in rabbits when given oral doses of 200 mg/kg/day. When methylphenidate was administered orally to rats throughout pregnancy and lactation at doses of up to 60 mg/kg/day, offspring growth and survival were decreased at maternally toxic doses. In a study in which oral methylphenidate was given to rats throughout pregnancy and lactation at doses up to 60 mg/kg/day, offspring weights and survival were decreased at 40 mg/kg/day and above; these doses caused some maternal toxicity.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of DAYTRANA 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 DAYTRANA for the treatment of ADHD have been established in pediatric patients 6 to 17 years. Long Term Suppression of Growth Growth should be monitored during treatment with stimulants, including DAYTRANA. Children who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions ( 5.8 )] . Juvenile Animal Toxicity 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. Studies with transdermal methylphenidate have not been performed in juvenile animals. In a 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 13-14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day or greater, and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose. The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day. The clinical significance of the long-term behavioral effects observed in rats is unknown.
Geriatric use
8.5 Geriatric Use DAYTRANA has not been studied in patients greater than 65 years of age.
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. Because methylphenidate has a large volume of distribution and is rapidly metabolized, dialysis is not useful. Remove all transdermal systems immediately and cleanse the area(s) to remove any remaining adhesive. The continuing absorption of methylphenidate from the skin, even after removal of the transdermal system, should be considered when treating patients with overdose. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
Description
11 DESCRIPTION DAYTRANA is an adhesive-based matrix transdermal system containing methylphenidate that is applied to intact skin. The chemical name for methylphenidate is α-phenyl-2-piperidineacetic acid methyl ester. It is a white to off-white powder and is soluble in alcohol, ethyl acetate, and ether. Methylphenidate is practically insoluble in water and petrol ether. Its molecular weight is 233.31. Its empirical formula is C 14 H 19 NO 2 . The structural formula of methylphenidate is: Transdermal System Components DAYTRANA contains methylphenidate in a multipolymeric adhesive. The methylphenidate is dispersed in acrylic adhesive that is dispersed in a silicone adhesive. The composition per unit area of all dosage strengths is identical, and the total dose delivered is dependent on the transdermal system size and wear time. DAYTRANA consists of three layers, as seen in the figure below (cross-section of the transdermal system). Proceeding from the outer surface toward the surface adhering to the skin, the layers are (1) a polyester/ethylene vinyl acetate laminate film backing, (2) a proprietary adhesive formulation incorporating Noven Pharmaceuticals, Inc.'s DOT Matrix™ transdermal technology consisting of an acrylic adhesive, a silicone adhesive, and methylphenidate, and (3) a fluoropolymer-coated polyester protective liner, which is attached to the adhesive surface and must be removed before the transdermal system can be used. The active component of the transdermal system is methylphenidate. The remaining components are pharmacologically inactive. daytrana-structure daytrana-figure-section
Mechanism of action
12.1 Mechanism of Action Methylphenidate is a CNS stimulant. Its mode of therapeutic action in ADHD is not known.
How supplied
16 HOW SUPPLIED/STORAGE AND HANDLING DAYTRANA is supplied in a sealed tray containing 30 individually pouched transdermal systems. See the chart below for information regarding available strengths. *Nominal in vivo delivery rate per hour in children and adolescents when applied to the hip, based on a 9-hour wear period. **Methylphenidate content in each transdermal system. Nominal Dose Delivered (mg) Over 9 Hours Dosage Rate* (mg/hr) Transdermal System Size (cm 2 ) Methylphenidate Content per Transdermal System** (mg) Transdermal Systems Per Carton NDC Number 10 1.1 12.5 27.5 30 68968-5552-3 15 1.6 18.75 41.3 30 68968-5553-3 20 2.2 25 55 30 68968-5554-3 30 3.3 37.5 82.5 30 68968-5555-3 Store at 25° C (77° F); excursions permitted to 15-30° C (59-86° F) [see USP Controlled Room Temperature]. Do not store transdermal systems unpouched. Do not store transdermal systems in refrigerators or freezers. Once the sealed tray is opened, use contents within 2 months. Apply the transdermal system immediately upon removal from the individual protective pouch. For transdermal use only. See the Patient Counseling Information ( 17 ) for specific disposal instructions for unused or expired DAYTRANA.
Patient information
Advise patients to read the FDA-approved patient labeling (Medication Guide and Instructions for Use). Abuse, Misuse, and Addiction Educate patients and their families about the risks of abuse, misuse, and addiction of DAYTRANA, which can lead to overdose and death, and proper disposal of any unused drug [see Warnings and Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 ), Overdosage ( 10 )] . Advise patients to store DAYTRANA in a safe place, preferably locked, and instruct patients to not give DAYTRANA to anyone else. Special Disposal Instructions Advise patients that there are special disposal instructions for unused or expired DAYTRANA [see Warnings and Precautions ( 5.1 )] . Instruct patients to find a take back location to dispose of unused or expired DAYTRANA. If a take back program is unavailable, instruct them to: Remove DAYTRANA from its pouch, separate it from its liner, fold it in half with the adhesive sides touching each other, and immediately flush it down the toilet, and Place the pouch and liner in a container, close the container, and throw out the container in the trash (advise patients not to flush the pouch and liner down the toilet). Risks to Patients with Serious Cardiac Disease Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with DAYTRANA use. Instruct patients to contact a healthcare 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 )] . 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 ( 5.6 )]. Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’s phenomenon] [see Warnings and Precautions ( 5.7 )] Instruct patients beginning treatment with DAYTRANA about the risk of peripheral vasculopathy, including Raynaud’s Phenomenon, and in 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 using DAYTRANA. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients. Long-Term Suppression of Growth in Pediatric Patients Advise patients that DAYTRANA may cause slowing of growth including weight loss [see Warnings and ( 5.8 )] . Chemical Leukoderma Advise patients of the possibility of a persistent loss of skin pigmentation at, around and distant from the application site. Advise patients to immediately inform their healthcare provider if changes in skin pigmentation occur [see Warnings and Precautions ( 5.9 )] . Increased Intraocular Pressure (IOP) and Glaucoma Advise patients that IOP and glaucoma may occur during treatment with DAYTRANA [see Warnings and Precautions ( 5.14 )] . Motor and Verbal Tics, and Worsening of Tourette’s Syndrome Advise patients that motor and verbal tics and worsening of Tourette’s Syndrome may occur during treatment with DAYTRANA. Instruct patients to notify their healthcare provider if emergence of new tics or worsening of tics or Tourette’s syndrome occurs [see Warnings and Precautions ( 5.15 )] . Important Preparation and Administration Instructions [see Dosage and Administration ( 2.3 )] Parents and patients should be informed to apply DAYTRANA to a clean, dry site on the hip, which is not oily, damaged, or irritated. The site of application must be alternated daily. DAYTRANA should not be applied to the waistline, or where tight clothing may rub it. If patients or caregivers experience difficulty separating the transdermal system from the release liner or observe tearing and/or other damage to the transdermal system during removal from the liner, the transdermal system should be discarded according to the directions provided in this label, and a new transdermal system should be applied [see Dosage and Administration ( 2.3 )] . Patients or caregivers should inspect the release liner to ensure that no adhesive containing medication has transferred to the liner. If adhesive transfer has occurred, the transdermal system should be discarded. DAYTRANA should be applied 2 hours before the desired effect. DAYTRANA should be removed approximately 9 hours after it is applied, although the effects from the transdermal system will last for several more hours. DAYTRANA may be removed earlier than 9 hours if a shorter duration of effect is desired or late day side effects appear. The parent or caregiver should be encouraged to use the administration chart included with each carton of DAYTRANA to monitor application and removal time, and method of disposal. The Medication Guide included at the end of this insert also includes a timetable to calculate when to remove DAYTRANA, based on the 9 hour application time. Patients or caregivers should avoid touching the adhesive side of the transdermal system during application, in order to avoid absorption of methylphenidate. If they do touch the adhesive side of the transdermal system, they should immediately wash their hands after application. In the event that a DAYTRANA does not fully adhere to the skin upon application, or is partially or fully detached during wear time, the transdermal system should be discarded according to the directions provided in this label, and a new transdermal system should be applied [see Dosage and Administration ( 2.3 )] . If a transdermal system is replaced, the total recommended wear time for that day should remain 9 hours, regardless of the number of transdermal systems used.
Label text from the FDA structured product label by Noven Therapeutics, LLC (revised Sep 1, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Methylphenidate in 4 products
Daytrana NDC products (4)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 68968-5552 | Methylphenidate 10 mg/9h Patch | Noven Therapeutics, LLC | NDA · DEA CII |
| 68968-5553 | Methylphenidate 15 mg/9h Patch | Noven Therapeutics, LLC | NDA · DEA CII |
| 68968-5554 | Methylphenidate 20 mg/9h Patch | Noven Therapeutics, LLC | NDA · DEA CII |
| 68968-5555 | Methylphenidate 30 mg/9h Patch | Noven Therapeutics, LLC | NDA · DEA CII |
Daytrana recalls
- D-0473-2023 Mar 29, 2023 · Class II · Ongoing
Defective Delivery System: Out of specification for shear. - D-0472-2023 Mar 29, 2023 · Class II · Ongoing
Defective Delivery System: Out of specification for shear. - D-0471-2023 Mar 29, 2023 · Class II · Ongoing
Defective Delivery System: Out of specification for shear. - D-0470-2023 Mar 29, 2023 · Class II · Ongoing
Defective Delivery System: Out of specification for shear. - D-0071-2023 Dec 7, 2022 · Class II · Ongoing
Defective Delivery System: Recalled lot was found to be out of specification for shear. Shear is an attribute related to the adhesive properties of the transdermal patches. - D-1169-2022 Jul 6, 2022 · Class II · Ongoing
Defective Delivery System: Customer complaints received for ripping patches and tight release/adhesive transfer. - D-0889-2022 Jun 1, 2022 · Class II · Ongoing
Defective Delivery System: customer complaints exceeded respective action limits. - D-0394-2021 Jun 2, 2021 · Class II · Ongoing
Defective Delivery System: The number of customer complaints for ripping patches and tight release/adhesive transfer have exceeded the action limits. - D-0393-2021 Jun 2, 2021 · Class II · Ongoing
Defective Delivery System: The number of customer complaints for ripping patches and tight release/adhesive transfer have exceeded the action limits. - D-0294-2021 Mar 10, 2021 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel. - D-0295-2021 Mar 10, 2021 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel. - D-0296-2021 Mar 10, 2021 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel. - D-0293-2021 Mar 10, 2021 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel. - D-1247-2020 Apr 29, 2020 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel and shear. - D-1248-2020 Apr 29, 2020 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel and shear. - D-1249-2020 Apr 29, 2020 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel and shear. - D-1045-2020 Mar 25, 2020 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel and shear. - D-1044-2020 Mar 25, 2020 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel and shear. - D-1043-2020 Mar 25, 2020 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel and shear. - D-1042-2020 Mar 25, 2020 · Class II · Terminated
Defective Delivery System: Out of specification for mechanical peel and shear.
Frequently asked questions
What is Daytrana used for?
(methylphenidate transdermal system) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 17 years of age. Limitations of Use The use of DAYTRANA 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…
What are the side effects of Daytrana?
Detailed information on serious and adverse reactions of particular importance is provided in the Boxed Warning and Warnings and Precautions ( 5 ) sections: Abuse, Misuse, and Addiction [see Boxed Warning ] Hypersensitivity to Methylphenidate [ see Contraindications ( 4.1 ) ] Monoamine Oxidase Inhibitors [ see Contraindications ( 4.2 ) and Drug Interactions ( 7.1 ) ] Risks to Patients with… See the full label for the complete list.
Who makes Daytrana?
Daytrana is listed by 1 labeler in the FDA NDC directory, including Noven Therapeutics, LLC.
Has Daytrana been recalled?
The FDA enforcement database lists 20 recalls for Daytrana, most recently D-0473-2023 (class ii): Defective Delivery System: Out of specification for shear.