Methylphenidate Hydrochloride: Package Insert and Label Information (Page 2 of 6)

5.7 Visual Disturbance

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

5.8 Potential for Gastrointestinal Obstruction

Because the methylphenidate hydrochloride extended-release tablet is nondeformable and does not appreciably change in shape in the GI tract, methylphenidate hydrochloride extended-release tablets should not ordinarily be administered to patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic, for example: esophageal motility disorders, small bowel inflammatory disease, “short gut” syndrome due to adhesions or decreased transit time, past history of peritonitis, cystic fibrosis, chronic intestinal pseudo-obstruction, or Meckel’s diverticulum). There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of drugs in nondeformable controlled-release formulations. Due to the controlled-release design of the tablet, methylphenidate hydrochloride extended-release tablets should be used only in patients who are able to swallow the tablet whole [see Patient Counseling Information (17)].

5.9 Hematologic Monitoring

Periodic CBC, differential, and platelet counts are advised during prolonged therapy.

6 ADVERSE REACTIONS

The following are discussed in more detail in other sections of the labeling:

Drug Dependence [see Box Warning]
Hypersensitivity to Methylphenidate [see Contraindications (4.1)]
Agitation [see Contraindications (4.2)]
Glaucoma [see Contraindications (4.3)]
Tics [see Contraindications (4.4)]
Monoamine Oxidase Inhibitors [see Contraindications (4.5) and Drug Interactions (7.1)]
Serious Cardiovascular Events [see Warnings and Precautions (5.1)]
Psychiatric Adverse Events [see Warnings and Precautions (5.2)]
Seizures [see Warnings and Precautions (5.3)]
Priapism [see Warnings and Precautions (5.4)]
Long-Term Suppression of Growth [see Warnings and Precautions (5.6)]
Visual Disturbance [see Warnings and Precautions (5.7)]
Potential for Gastrointestinal Obstruction [see Warnings and Precautions (5.8)]
Hematologic Monitoring [see Warnings and Precautions (5.9)]

The most common adverse reaction in double-blind clinical trials (>5%) in pediatric patients (children and adolescents) was abdominal pain upper. The most common adverse reactions in double-blind clinical trials (>5%) in adult patients were decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis [see Adverse Reactions (6.1)].

The most common adverse reactions associated with discontinuation (≥1%) from either pediatric or adult clinical trials were anxiety, irritability, insomnia, and blood pressure increased [see Adverse Reactions (6.3)].

The development program for methylphenidate hydrochloride extended-release tablets included exposures in a total of 3906 participants in clinical trials. Children, adolescents, and adults with ADHD were evaluated in 6 controlled clinical studies and 11 open-label clinical studies (see Table 3). Safety was assessed by collecting adverse events, vital signs, weights, and ECGs, and by performing physical examinations and laboratory analyses.

Table 3. Methylphenidate Hydrochloride Extended-Release Tablets Exposure in Double-Blind and Open-Label Clinical Studies

Patient Population

N

Dose Range

Children

2216

18 to 54 mg once daily

Adolescents

502

18 to 72 mg once daily

Adults

1188

18 to 108 mg once daily

Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using their own terminology. Consequently, to provide a meaningful estimate of the proportion of individuals experiencing adverse events, events were grouped in standardized categories using MedDRA terminology.

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.

Throughout this section, adverse reactions are reported. Adverse reactions are adverse events that were considered to be reasonably associated with the use of methylphenidate hydrochloride extended-release tablets based on the comprehensive assessment of the available adverse event information. A causal association for methylphenidate hydrochloride extended-release tablets often cannot be reliably established in individual cases. Further, 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 clinical trials of another drug and may not reflect the rates observed in clinical practice.

The majority of adverse reactions were mild to moderate in severity.

6.1 Commonly Observed Adverse Reactions in Double-Blind, Placebo-Controlled Clinical Trials

Adverse reactions in either the pediatric or adult double-blind adverse reactions tables may be relevant for both patient populations.

Children and Adolescents

Table 4 lists the adverse reactions reported in 1% or more of methylphenidate hydrochloride extended-release tablets-treated children and adolescent subjects in 4 placebo-controlled, double-blind clinical trials.

Table 4. Adverse Reactions Reported by ≥1% of Methylphenidate Hydrochloride Extended-Release Tablets-Treated Children and Adolescent Subjects in 4 Placebo-Controlled, Double-Blind Clinical Trials of Methylphenidate Hydrochloride Extended-Release Tablets

System/Organ Class Adverse Reaction

Methylphenidate Hydrochloride Extended-Release Tablets (n=321) %

Placebo (n=318) %

Gastrointestinal Disorders

Abdominal pain upper

6.2

3.8

Vomiting

2.8

1.6

General Disorders and Administration Site Conditions

Pyrexia

2.2

0.9

Infections and Infestations

Nasopharyngitis

2.8

2.2

Nervous System Disorders

Dizziness

1.9

0

Psychiatric Disorders

Insomnia*

2.8

0.3

Respiratory, Thoracic and Mediastinal Disorders

Cough

1.9

0.9

Oropharyngeal pain

1.2

0.9

* Terms of Initial insomnia (methylphenidate hydrochloride extended-release tablets=0.6%) and Insomnia (methylphenidate hydrochloride extended-release tablets=2.2%) are combined into Insomnia.

The majority of adverse reactions were mild to moderate in severity.

Adults

Table 5 lists the adverse reactions reported in 1% or more of methylphenidate hydrochloride extended-release tablets-treated adults in 2 placebo-controlled, double-blind clinical trials.

Table 5. Adverse Reactions Reported by ≥1% of Methylphenidate Hydrochloride Extended-Release Tablets-Treated Adult Subjects in 2 Placebo-Controlled, Double-Blind Clinical Trials*

System/Organ Class Adverse Reaction

Methylphenidate Hydrochloride Extended-Release Tablets (n=415) %

Placebo (n=212) %

Cardiac Disorders

Tachycardia

4.8

0

Palpitations

3.1

0.9

Ear and Labyrinth Disorders

Vertigo

1.7

0

Eye Disorders

Vision blurred

1.7

0.5

Gastrointestinal Disorders

Dry mouth

14.0

3.8

Nausea

12.8

3.3

Dyspepsia

2.2

0.9

Vomiting

1.7

0.5

Constipation

1.4

0.9

General Disorders and Administration Site Conditions

Irritability

5.8

1.4

Infections and Infestations

Upper respiratory tract infection

2.2

0.9

Investigations

Weight decreased

6.5

3.3

Metabolism and Nutrition Disorders

Decreased appetite

25.3

6.6

Anorexia

1.7

0

Musculoskeletal and Connective Tissue Disorders

Muscle tightness

1.9

0

Nervous System Disorders

Headache

22.2

15.6

Dizziness

6.7

5.2

Tremor

2.7

0.5

Paresthesia

1.2

0

Sedation

1.2

0

Tension headache

1.2

0.5

Psychiatric Disorders

Insomnia

12.3

6.1

Anxiety

8.2

2.4

Initial insomnia

4.3

2.8

Depressed mood

3.9

1.4

Nervousness

3.1

0.5

Restlessness

3.1

0

Agitation

2.2

0.5

Aggression

1.7

0.5

Bruxism

1.7

0.5

Depression

1.7

0.9

Libido decreased

1.7

0.5

Affect lability

1.4

0.9

Confusional state

1.2

0.5

Tension

1.2

0.5

Respiratory, Thoracic and Mediastinal Disorders

Oropharyngeal pain

1.7

1.4

Skin and Subcutaneous Tissue Disorders

Hyperhidrosis

5.1

0.9

*Included doses up to 108 mg.

The majority of ADRs were mild to moderate in severity

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