The following are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Boxed Warning , Warnings and Precautions (5.1) , and Drug Abuse and Dependence (9.2 , 9.3) ] Hypersensitivity to Methylphenidate [see Contraindications (4) ] Hypertensive Crisis with Concomitant Use of Monoamine Oxidase Inhibitors [see Contraindications (4) 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) ] Priapism [see Warnings and Precautions (5.5) ] Peripheral Vasculopathy, including Raynaud's Phenomenon [see Warnings and Precautions (5.6) ] Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions (5.7) ] Acute Angle Closure Glaucoma [see Warnings and Precautions (5.8) ] Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions (5.9) ] Motor and Verbal Tics, and Worsening of Tourette's Syndrome [see Warnings and Precautions (5.10) ] The most common adverse reactions in double-blind clinical trials (> 5% and twice the rate of placebo) in pediatric patients 6 to 17 years were abdominal pain, decreased appetite, headache and insomnia.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Rhodes Pharmaceuticals LLC at 1-888-873-5329; or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adverse Reactions in Studies with Other Methylphenidate Products in Children, Adolescents, and Adults with ADHD Commonly reported (≥2% of the methylphenidate group and at least twice the rate of the placebo group) adverse reactions from placebo-controlled trials of methylphenidate products include: decreased appetite, decreased weight, nausea, abdominal pain, dyspepsia, dry mouth, vomiting, insomnia, anxiety, nervousness, restlessness, affect lability, agitation, irritability, dizziness, vertigo, tremor, blurred vision, increased blood pressure, increased heart rate, tachycardia, palpitations, hyperhidrosis, and pyrexia.
Adverse Reactions in Studies with Methylphenidate Hydrochloride Extended-Release Capsules in Pediatric Patients with ADHD The safety data in this section is based on data from two one-week controlled clinical studies of methylphenidate hydrochloride extended-release capsules in pediatric patients with ADHD, one in children ages 6 to 12 years (RP-BP-EF001, hereafter "Study 1"), and one in children and adolescents ages 6 to 17 years (RP-BP-EF002, hereafter "Study 2").
Two methylphenidate hydrochloride extended-release capsules clinical studies evaluated a total of 256 patients with ADHD. Two hundred and forty-three (243) patients participated in the double-blind phase of these two clinical studies. Study 1 was a randomized, double-blind, single center, placebo-controlled, flexible-dose, cross-over study to evaluate the time of onset, duration of efficacy, tolerability and safety of methylphenidate hydrochloride extended-release capsules 15 mg, 20 mg, 30 mg, or 40 mg administered for one week in 26 pediatric patients aged 6 to 12 years who met DSM-IV criteria for ADHD [see Clinical Studies (14) ] .
Most Common Adverse Reactions (incidence of ≥ 5% and at a rate at least twice placebo): abdominal pain, pyrexia and headache. Adverse Reactions Leading to Discontinuation: No subjects discontinued due to adverse reactions during the double-blind phase of this study. Study 2 was a randomized, double-blind, multicenter, placebo-controlled, parallel group, fixed-dose study of 10 mg, 15 mg, 20 mg, and 40 mg of methylphenidate hydrochloride extended-release capsules administered for one week in 221 pediatric patients (6 to 17 years of age) who met DSM-IV criteria for ADHD [see Clinical Studies (14) ] .
Most Common Adverse Reactions (incidence of ≥ 5% and at a rate of at least twice placebo): abdominal pain, decreased appetite, headache and insomnia. Adverse Reactions Leading to Discontinuation: Two patients (4.4%) in the methylphenidate hydrochloride extended-release capsules 40 mg group discontinued due to insomnia, nausea and rapid heart rate, respectively during the double-blind phase of the study. Table 1: Common Adverse Reactions Occurring in ≥ 2% of Pediatric Patients (6 to 17 years of age) with ADHD Taking Methylphenidate Hydrochloride Extended-Release Capsules and at a Rate Greater than Placebo (Study 2) System Organ Class Adverse Reaction Methylphenidate Hydrochloride Extended-Release Capsules (n=183) Placebo (n=47) Nervous System Disorders Headache 10.9% 8.5% Insomnia 9.8% 2.1% Dizziness 2.2% 2.1% Gastrointestinal Disorders Abdominal pain upper 8.2% 0% Nausea 3.8% 2.1% Vomiting 3.8% 0% Metabolism and Nutritional Decreased Appetite 4.9% 0%
6.2Post-Marketing 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, 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 NEC, Rashes, Eruptions, and Exanthems NEC 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 : Convulsion, Grand mal convulsion, Dyskinesia, serotonin syndrome in combination with serotonergic drugs, Motor and Verbal Tics Psychiatric Disorders : Disorientation, Libido changes Skin and Subcutaneous Tissue Disorders : Alopecia, Erythema
