The pre-marketing development program for Focalin included exposures in a total of 696 participants in clinical trials (684 patients, 12 healthy adult subjects). These participants received Focalin 5, 10, or 20 mg/day. The 684 ADHD patients (ages 6 to 17 years) were evaluated in two controlled clinical studies, two clinical pharmacology studies, and two uncontrolled long-term safety studies. Safety data on all patients are included in the discussion that follows. Adverse reactions were assessed by collecting adverse events, and results of physical examinations, vital sign and body weight measurements, and laboratory analyses.
Adverse events during exposure were primarily obtained by general inquiry and recorded by 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 events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, standard COSTART dictionary terminology has been used to classify reported adverse events.
The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.
Adverse Findings In Clinical Trials with Focalin
Adverse Events Associated with Discontinuation of Treatment
No Focalin-treated patients discontinued due to adverse events in two placebo-controlled trials. Overall, 50 of 684 children treated with Focalin (7.3%) experienced an adverse event that resulted in discontinuation. The most common reasons for discontinuation were twitching (described as motor or vocal tics), anorexia, insomnia, and tachycardia (approximately 1% each).
Adverse Events Occurring at an Incidence of 5% or More Among Focalin-Treated Patients
Table 1 enumerates treatment-emergent adverse events for two, placebo-controlled, parallel group trials in children with ADHD at Focalin doses of 5, 10, and 20 mg/day. The table includes only those events that occurred in 5% or more of patients treated with Focalin where the incidence in patients treated with Focalin was at least twice the incidence in placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.
Table 1 : Treatment-Emergent Adverse Events1 Occurring During Double-Blind Treatment in Clinical Trials of Focalin®
|Body System||Preferred Term||Focalin
|Body as a Whole|
|1 Events, regardless of causality, for which the incidence for patients treated with Focalin was at least 5% and twice the incidence among placebo-treated patients. Incidence has been rounded to the nearest whole number.|
Adverse Events From Post-Marketing Experience
The following additional adverse reactions have been identified during postapproval use of Focalin XR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency:
Immune System Disorders: hypersensitivity reactions, including angioedema and anaphylaxis
Adverse Events With Other Methylphenidate HCl Products
Nervousness and insomnia are the most common adverse reactions reported with other methylphenidate products. In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia may occur more frequently; however, any of the other adverse reactions listed below may also occur.
Other Reactions Include
Cardiac: angina, arrhythmia, palpitations, pulse increased or decreased, tachycardia
Immune: hypersensitivity reactions including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura
Nervous System: dizziness, drowsiness, dyskinesia, headache, rare reports of Tourette's syndrome, toxic psychosis
Vascular: blood pressure increased or decreased, cerebral arteritis and/or occlusion
Although a definite causal relationship has not been established, the following have been reported in patients taking methylphenidate:
Blood/lymphatic: leukopenia and/or anemia
Hepatobiliary: abnormal liver function, ranging from transaminase elevation to hepatic coma
Psychiatric: transient depressed mood, aggressive behavior, libido changes
Skin/subcutaneous: scalp hair loss
Urogenital System: priapism
Very rare reports of neuroleptic malignant syndrome (NMS) have been received, and, in most of these, patients were concurrently receiving therapies associated with NMS. In a single report, a ten year old boy who had been taking methylphenidate for approximately 18 months experienced an NMS-like event within 45 minutes of ingesting his first dose of venlafaxine. It is uncertain whether this case represented a drug-drug interaction, a response to either drug alone, or some other cause.
In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia may occur more frequently; however, any of the other adverse reactions listed above may also occur.
Drug Abuse And Dependence
Controlled Substance Class
Focalin, like other methylphenidate products, is classified as a Schedule II controlled substance by Federal regulation.
Abuse, Dependence, And Tolerance
See WARNINGS for boxed warning containing drug abuse and dependence information.