Jornay Drug Information

Pretreatment Screening

Prior to treating patients with JORNAY PM, assess: for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) . the family history and clinically evaluate patients for motor or verbal tics or Tourette's syndrome.

Recommended Dosage

The recommended starting dosage of JORNAY PM in patients 6 years and older is 20 mg once daily orally in the evening. Do not take JORNAY PM in the morning. The dose may be titrated weekly in increments of 20 mg.

A daily dosage above 100 mg has not been studied and is not recommended. Initiate dosing at 8:00 p.m. Adjust the timing of administration between 6:30 p.m. and 9:30 p.m. to optimize the tolerability and efficacy the next morning and throughout the day.

In clinical trials of patients aged 6 to 12 years, the most common dosing time (>70% of patients) was 8:00 p.m., with an allowed range between 6:30 p.m. and 9:30 p.m. Following determination of the optimal administration time, advise patients to maintain a consistent dosing time. Advise patients to take JORNAY PM consistently, either with food or without food.

Patients who miss their dose of JORNAY PM at the regularly scheduled time should take it as soon as they remember that same evening. If a patient remembers the missed dose the following morning, they should skip the missed dose and wait until their next scheduled evening administration.

Administration Instructions

JORNAY PM may be taken whole, or the capsule may be opened, and the entire contents sprinkled onto applesauce. If the patient is using the sprinkled administration method, the sprinkled applesauce should be consumed immediately; it should not be stored. Patients should take the applesauce with sprinkled beads in its entirety without chewing.

The dose of a single capsule should not be divided. The contents of the entire capsule should be taken at the same time.

Switching from Other Methylphenidate Products

If switching from other methylphenidate products, discontinue that treatment, and titrate with JORNAY PM using the titration schedule described above. Do not substitute JORNAY PM for other methylphenidate products on a milligram-per-milligram basis because these products have different pharmacokinetic profiles from JORNAY PM and may have different methylphenidate base composition .

Dosage Reduction and Discontinuation

If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage or, if necessary, discontinue JORNAY PM. If improvement is not observed after appropriate dosage adjustment over a one-month period, discontinue JORNAY PM.

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 with 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 JORNAY PM in Pediatric Patients (6 to 12 years) with ADHD The safety of JORNAY PM was evaluated in 280 patients (6 to 12 years of age) who participated in two controlled clinical studies of patients with ADHD . Study 1, conducted in pediatric patients 6 to 12 years of age, was comprised of a 6-week open-label dose-optimization phase in which all patients received JORNAY PM (n=125; mean dose 50 mg), followed by a 1-week, double-blind controlled phase in which patients were randomized to continue JORNAY PM (n=65) or switch to placebo (n=54). During the open-label JORNAY PM treatment phase, adverse reactions reported in > 5% of patients included: any insomnia (41%), decreased appetite (27%), affect lability (22%), headache (19%), upper respiratory tract infection (17%), upper abdominal pain (9%), nausea or vomiting (9%), increased diastolic blood pressure (8%), tachycardia (7%), and irritability (6%). Three patients discontinued treatment because of adverse reactions of affect lability, panic attacks, and agitation and aggression.

Because of the trial design (6-week open-label active treatment phase followed by a 1-week, randomized, double-blind, placebo-controlled withdrawal), the adverse reaction rates described in the double-blind phase are lower than expected in clinical practice. No difference occurred in the incidence of adverse reactions between JORNAY PM and placebo during the 1-week, double-blind, placebo-controlled treatment phase. Study 2 was a 3-week, placebo-controlled study of JORNAY PM (n=81; mean dose 52mg) in pediatric patients 6 to 12 years.

Most Common Adverse Reactions (incidence of ≥ 5% and at a rate at least twice placebo): any insomnia, decreased appetite, headache, vomiting, nausea, psychomotor hyperactivity, and affect lability or mood swings. One patient in the JORNAY PM group discontinued from the study due to mood swings. Table 1 provides the incidence of adverse reactions reported in Study 2 (incidence of 2% or more and at least twice placebo) among pediatric patients 6 to 12 years in a 3-week clinical trial.

Table 1: Adverse Reactions that Occurred in ≥2% of JORNAY PM-treated Pediatric Patients and Greater than Placebo in a 3-Week ADHD Study (Study 2) Body Organ System Adverse Reaction JORNAY PM (N=81) Placebo (N=80) Psychiatric disorders Any insomnia 33% 9% Initial insomnia 14% 5% Middle insomnia 11% 4% Terminal insomnia 11% 1% Insomnia, not specified 4% 1% Affect lability/ Mood swings 6% 1% Metabolism and nutrition disorders Decreased appetite 19% 4% Nervous system disorders Headache 10% 5% Psychomotor hyperactivity 5% 1% Cardiovascular Blood pressure diastolic increased 7% 4% Gastrointestinal disorders Vomiting 9% 0% Nausea 6% 0% Infections and infestations Nasopharyngitis Pharyngitis streptococcal 3% 3% 1% 0% Injury, poisoning and procedural complications Contusion 3% 0% Musculoskeletal and connective tissue disorders Back pain 3% 0% Skin and subcutaneous tissue disorders Rash 2% 0%

Postmarketing Experience

The following adverse reactions have been identified during postapproval 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, Increased intraocular pressure, Mydriasis, Visual impairment General Disorders: Chest pain, Chest discomfort, Hyperpyrexia Immune System Disorders: Hypersensitivity reactions such as Angioedema, Anaphylactic reactions, Auricular swelling, Bullous conditions, Exfoliative conditions, Urticarias, Pruritus, Rashes, Eruptions, and Exanthemas Investigations: Alkaline phosphatase increased, Bilirubin increased, Hepatic enzyme increased, Platelet count decreased, White blood cell count abnormal, Severe hepatic injury 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, Motor and Verbal Tics 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

MAO Inhibitors Do not administer

JORNAY PM concomitantly with MAOIs or within 14 days after discontinuing MAOI treatment. Concomitant use of MAO inhibitors 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

JORNAY PM may decrease the effectiveness of drugs used to treat hypertension. Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed.

Halogenated Anesthetics

Concomitant use of halogenated anesthetics and JORNAY PM may increase the risk of sudden blood pressure and heart rate increase during surgery. Monitor blood pressure and avoid use of JORNAY PM in patients being treated with anesthetics on the day of surgery.

Risperidone

The combined use of methylphenidate with risperidone when there is a change in dose of either or both medications may increase the risk of extrapyramidal symptoms (EPS). Monitor for signs of EPS.

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to JORNAY PM during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388. Risk Summary Published studies and postmarketing reports on methylphenidate use during pregnancy are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes . No teratogenic effects were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis at doses up to 2 and 9 times the maximum recommended human dose (MRHD) of 100 mg/day given to adolescents on a mg/m 2 basis, respectively. However, spina bifida was observed in rabbits at a dose 31 times the MRHD given to adolescents.

A decrease in pup body weight was observed in a pre-and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 3.5 times the MRHD given to adolescents . The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies. Clinical Considerations Fetal/Neonatal Adverse Reactions CNS stimulant medications, such as JORNAY PM, 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 Human Data A limited number of pregnancies have been reported in published observational studies and postmarketing reports describing methylphenidate use during pregnancy. Due to the small number of methylphenidate-exposed pregnancies with known outcomes, these data cannot definitely establish or exclude any drug-associated risk during pregnancy.

Methodological limitations of these observational studies include small sample size, concomitant use of other medications, lack of detail regarding dose and duration of exposure to methylphenidate and nongeneralizability of the enrolled populations. 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 31 times the maximum recommended human dose (MRHD) of 100 mg/day given to adolescents on a mg/m 2 basis.

The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (9 times the MRHD given to adolescents 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 (6 times the MRHD given to adolescents 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 given to adolescents on a mg/m 2 basis).

Pediatric Use The safety and effectiveness of JORNAY PM 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 JORNAY PM have been established in pediatric patients ages 6 to 17 years in two adequate and well-controlled clinical studies in pediatric patients 6 to 12 years, pharmacokinetic data in adults, and safety information from other methylphenidate-containing products. Long-Term Suppression of Growth Growth should be monitored during treatment with stimulants, including JORNAY PM. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted. 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. The doses at which these findings were observed are at least 2.5 times the maximum recommended human dose (MRHD) of 100 mg/day given to children on a mg/m 2 basis. 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 (approximately ≥ 2.5 times the MRHD of 100 mg/day given to children on a mg/m 2 basis), and a deficit in the acquisition of a specific learning task was seen in females exposed to the highest dose (5 times the MRHD of 100 mg/day given to children on a mg/m 2 basis). The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (0.25 times the MRHD of 100 mg/day given to children on a mg/m 2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.

is contraindicated in patients: With a history of hypersensitivity to methylphenidate or other components of JORNAY PM. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate products. Receiving concomitant treatment with monoamine oxidase (MAO) inhibitors, or within 14 days following discontinuation of a monoamine oxidase inhibitor, because of the risk of hypertensive crisis . Known hypersensitivity to methylphenidate or product components. Concurrent treatment with a monoamine oxidase inhibitor (MAOI) or use of an MAOI within the preceding 14 days.

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℉) and rhabdomyolysis may develop.

Overdose Management Consider the possibility of multiple drug ingestion. The pharmacokinetic profile of JORNAY PM 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.