ADHANSIA XR SIDE EFFECTS
- Generic Name: methylphenidate hydrochloride extended-release capsules
- Brand Name: Adhansia XR
SIDE EFFECTS
The following are discussed in more detail in other sections of the labeling:
- Known hypersensitivity to methylphenidate or other ingredients of ADHANSIA XR .
- Hypertensive crisis when used concomitantly with monoamine oxidase inhibitors.
- Drug dependence.
- Serious cardiovascular reactions.
- Blood pressure and heart rate increases.
- Psychiatric adverse reactions.
- Priapism.
- Peripheral vasculopathy, including Raynaud’s phenomenon.
- Long-term suppression of growth.
- Allergic Reactions FD&C Yellow No.5.
Clinical Trial 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 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 ADHANSIA XR
ADHANSIA XR was studied in adults (18 to 72 years) and pediatric patients (6 to 17 years) who met Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) criteria for ADHD.
The safety data for adults is based on two randomized, double-blind, placebo-controlled studies in doses of 25 mg to 100 mg per day. The safety data for pediatric patients (6 to 17 years) is based on randomized, double-blind, placebo-controlled studies in doses of 25 mg to 85 mg per day.
The total number of patients exposed to ADHANSIA XR during 1 to 4-week long, controlled treatment periods is 883; this included 434 adult patients and 449 pediatric patients [156 (6 to 12 years); 293 (12 to 17 years)], from two clinical trials in adults, one in pediatric patients ages 12 to 17 years, and one in pediatric patients ages 6 to 12 years.
Adverse Reactions Leading To Discontinuation Of Treatment
In controlled adult trials for Study 1, 3% of both of ADHANSIA XR-treated patients and placebo-treated patients discontinued due to adverse reactions. In an adult workplace environment study (Study 2), 10% of ADHANSIA XR-treated patients discontinued due to adverse reactions compared to 0% of placebo-treated patients. The following adverse reactions led to discontinuation at a frequency of 2% of ADHANSIA XR-treated patients: nausea, bronchitis, gastroenteritis viral, viral infection, blood pressure increased, and hypomania.
In a controlled trial (Study 3) in pediatric patients (12 to 17 years), 3% of ADHANSIA XR-treated patients discontinued due to adverse reactions compared to 0% of placebo-treated patients. The most frequent adverse reactions leading to discontinuation in at least 1% of ADHANSIA XR-treated patients and at a rate greater that placebo was irritability (1%). Two patients taking ADHANSIA XR 70 or 85 mg had delirium leading to discontinuation.
In a controlled trial (Study 4) in pediatric patients (6 to 12 years), 1% of ADHANSIA XR-treated patients discontinued due to adverse reactions compared to 0% of placebo-treated patients.
Adult Patients With ADHD
The most common adverse reactions (incidence of ≥5% and at least twice placebo) of ADHANSIA XR occurring in controlled trials in adults were insomnia, dry mouth, and decreased appetite.
Table 1 lists the adverse reactions that occurred ≥2% of adult patients and greater than placebo among ADHANSIA XR-treated adult patients.
Table 1: Adverse Reactions Occurring in ≥ 2% of Adult Patients with ADHD on ADHANSIA XR and Greater than Patients Taking Placebo in a 4-week Clinical Trial
| Adverse Reaction | ADHANSIA XR | All doses ADHANSIA XR | Placebo | |||
| 25 mg | 45 mg | 70 mg | 100 mg | |||
| N=375 | (N=77) | (N=73) | (N=73) | (N=74) | (N=297) | (N=78) |
| Initial Insomnia | 4% | 8% | 6% | 7% | 6% | 1% |
| Insomnia | 17% | 11% | 16% | 19% | 16% | 4% |
| Dry mouth | 8% | 8% | 7% | 14% | 9% | 4% |
| Nausea | 4% | 6% | 4% | 11% | 6% | 3% |
| Diarrhea | 1% | 3% | 7% | 5% | 4% | 1% |
| Decreased appetite | 4% | 7% | 15% | 19% | 11% | 3% |
| Feeling jittery | 1% | 3% | 8% | 4% | 4% | 1% |
| Weight decreased | 3% | 4% | 3% | 5% | 4% | 1% |
| Upper respiratory tract infection | 0% | 4% | 3% | 3% | 2% | 1% |
Pediatric Patients (12 To 17 Years) With ADHD
The most common (incidence ≥5% and at least twice placebo) adverse reactions reported in pediatric patients (12 to 17 years) were decreased appetite, insomnia, and weight decreased.
Table 2 lists the adverse reactions that occurred ≥2% of pediatric patients (12 to 17 years) and greater than placebo among ADHANSIA XR-treated pediatric patients (12 to 17 years).
Table 2: Adverse Reactions Occurring in ≥ 2% of Pediatric Patients (12 to 17 years) with ADHD Taking ADHANSIA XR and Greater than Placebo in a 4-week Clinical Trial
| Adverse Reaction | ADHANSIA XR | All doses ADHANSIA XR | Placebo | |||
| 25 mg | 45 mg | 70 mg | 85 mg | |||
| (N=73) | (N=72) | (N=76) | (N=72) | (N=293) | (N=74) | |
| Decreased appetite | 7% | 19% | 28% | 26% | 20% | 0% |
| Insomnia | 4% | 0% | 9% | 13% | 6% | 1% |
| Initial Insomnia | 4% | 7% | 5% | 4% | 5% | 1% |
| Weight decreased | 1% | 3% | 8% | 13% | 7% | 0% |
| Abdominal pain upper | 5% | 1% | 5% | 4% | 4% | 1% |
| Nausea | 3% | 6% | 7% | 8% | 6% | 4% |
| Dizziness | 3% | 0% | 4% | 4% | 3% | 0% |
| Dry mouth | 1% | 0% | 5% | 4% | 3% | 1% |
| Vomiting | 1% | 1% | 3% | 6% | 3% | 0% |
Pediatric Patients (6 To 12 Years) With ADHD
Study 4, 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 ADHANSIA XR (n=156; mean dose 48 mg), followed by a 1-week, double-blind controlled phase in which patients were randomized to continue ADHANSIA XR (n=75) or switch to placebo (n=73). During the open-label ADHANSIA XR treatment phase, adverse reactions reported in > 5% of patients included: decreased appetite (35%), upper abdominal pain (15%), affect lability (13%), nausea or vomiting (13%), weight decreased (12%), insomnia (10%), irritability (10%), headache (10%), and heart rate increased (5%). 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 ADHANSIA XR and placebo during the 1-week, double-blind, placebo-controlled treatment phase.
Post-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, mydriasis, visual impairment
General Disorders: chest pain, chest discomfort, hyperpyrexia
Hepatobiliary disorders: hepatocellular injury, acute hepatic failure
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
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, logorrhea, mania
Skin and Subcutaneous Tissue Disorders: alopecia, erythema
Urogenital System: priapism
Vascular Disorders: Raynaud’s phenomenon
SRC: NLM .