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Methylphenidate (Methylphenidate Hydrochloride) - Side Effects and Adverse Reactions

 
 



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]
  • Agitation [see Contraindications]
  • Glaucoma [see Contraindications]
  • Tics [see Contraindications]
  • Monoamine Oxidase Inhibitors [see Contraindications and Drug Interactions]
  • Serious Cardiovascular Events [see Warnings and Precautions]
  • Psychiatric Adverse Events [see Warnings and Precautions]
  • Seizures [see Warnings and Precautions]
  • Priapism [see Warnings and Precautions]
  • Long-Term Suppression of Growth [see Warnings and Precautions]
  • Visual Disturbance [see Warnings and Precautions]
  • Potential for Gastrointestinal Obstruction [see Warnings and Precautions]
  • Hematologic Monitoring [see Warnings and Precautions]

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].

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].

The development program for Methylphenidate HCl 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, ECGs, and by performing physical examinations and laboratory analyses.

Table 3. Methylphenidate HCl 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 HCl Extended-Release Tablets based on the comprehensive assessment of the available adverse event information. A causal association for Methylphenidate HCl 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.

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 HCl 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 HCl Extended-Release Tablets -Treated Children and Adolescent Subjects in 4 Placebo-Controlled, Double-Blind Clinical Trials of Methylphenidate HCl Extended-Release Tablets
System/Organ Class
  Adverse Reaction
Methylphenidate HCl 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 1  2.8  0.3
 Respiratory, Thoracic and Mediastinal Disorders    
   Cough  1.9  0.9
   Oropharyngolaryngeal pain  1.2  0.9

1 Terms of Initial insomnia (Methylphenidate=0.6%) and Insomnia (Methylphenidate=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 HCl Extended-Release Tablets -treated adults in 2 placebo-controlled, double-blind clinical trials.

Table 5. Adverse Reactions Reported by ≥1% of Methylphenidate HCl Extended-Release Tablets -Treated Adult Subjects in 2 Placebo-Controlled, Double-Blind Clinical Trials 1
System/Organ Class
  Adverse Reaction
Methylphenidate HCl 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 Administation 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    
   Oropharyngolaryngeal pain  1.7  1.4
 Skin and Subcutaneous Tissue Disorders    
   Hyperhidrosis  5.1  0.9

1 Included doses up to 108 mg.

The majority of ADRs were mild to moderate in severity.

Other Adverse Reactions Observed in Methylphenidate HCl Extended-Release Tablets Clinical Trials

This section includes adverse reactions reported by Methylphenidate HCl Extended-Release Tablets-treated subjects in double-blind trials that do not meet the criteria specified for Table 4 or Table 5 and all adverse reactions reported by Methylphenidate HCl Extended-Release Tablets-treated subjects who participated in open-label and postmarketing clinical trials.

Blood and Lymphatic System Disorders: Leukopenia

Eye Disorders: Accommodation disorder, Dry eye

Vascular Disorders: Hot flush

Gastrointestinal Disorders: Abdominal discomfort, Abdominal pain, Diarrhea

General Disorders and Administrative Site Conditions: Asthenia, Fatigue, Feeling jittery, Thirst

Infections and Infestations: Sinusitis

Investigations: Alanine aminotransferase increased, Blood pressure increased, Cardiac murmur, Heart rate increased

Musculoskeletal and Connective Tissue Disorders: Muscle spasms

Nervous System Disorders: Lethargy, Psychomotor hyperactivity, Somnolence

Psychiatric Disorders: Anger, Hypervigilance, Mood altered, Mood swings, Panic attack, Sleep disorder, Tearfulness, Tic

Reproductive System and Breast Disorders: Erectile dysfunction

Respiratory, Thoracic and Mediastinal Disorders: Dyspnea

Skin and Subcutaneous Tissue Disorders: Rash, Rash macular

Vascular Disorders: Hypertension

Discontinuation Due to Adverse Reactions

Adverse reactions in the 4 placebo-controlled studies of children and adolescents leading to discontinuation occurred in 2 Methylphenidate HCl Extended-Release Tablets patients (0.6%) including depressed mood (1, 0.3%) and headache and insomnia (1, 0.3%), and 6 placebo patients (1.9%) including headache and insomnia (1, 0.3%), irritability (2, 0.6%), headache (1, 0.3%) psychomotor hyperactivity (1, 0.3%), and tic (1, 0.3%).

In the 2 placebo-controlled studies of adults, 25 Methylphenidate HCl Extended-Release Tablets patients (6.0%) and 6 placebo patients (2.8%) discontinued due to an adverse reaction. Those events with an incidence of >0.5% in the Methylphenidate HCl Extended-Release Tablets patients included anxiety (1.7%), irritability (1.4%), blood pressure increased (1.0%), and nervousness (0.7%). In placebo patients, blood pressure increased and depressed mood had an incidence of >0.5% (0.9%).

In the 11 open-label studies of children, adolescents and adults, 266 Methylphenidate HCl Extended-Release Tablets patients (7.0%) discontinued due to an adverse reaction. Those events with an incidence of >0.5% included insomnia (1.2%), irritability (0.8%), anxiety (0.7%), decreased appetite (0.7%), and tic (0.6%).

Tics

In a long-term uncontrolled study (n=432 children), the cumulative incidence of new onset of tics was 9% after 27 months of treatment with Methylphenidate HCl Extended-Release Tablets.

In a second uncontrolled study (n=682 children) the cumulative incidence of new onset tics was 1% (9/682 children). The treatment period was up to 9 months with mean treatment duration of 7.2 months.

Blood Pressure and Heart Rate Increases

In the laboratory classroom clinical trials in children (Studies 1 and 2), both Methylphenidate HCl Extended-Release Tablets once daily and methylphenidate three times daily increased resting pulse by an average of 2 to 6 bpm and produced average increases of systolic and diastolic blood pressure of roughly 1 to 4 mm Hg during the day, relative to placebo. In the placebo-controlled adolescent trial (Study 4), mean increases from baseline in resting pulse rate were observed with Methylphenidate HCl Extended-Release Tablets and placebo at the end of the double-blind phase (5 and 3 beats/minute, respectively). Mean increases from baseline in blood pressure at the end of the double-blind phase for Methylphenidate HCl Extended-Release Tablets and placebo-treated patients were 0.7 and 0.7 mm Hg (systolic) and 2.6 and 1.4 mm Hg (diastolic), respectively. In one placebo-controlled study in adults (Study 6), dose-dependent mean increases of 3.9 to 9.8 bpm from baseline in standing pulse rate were observed with Methylphenidate HCl Extended-Release Tablets at the end of the double-blind treatment vs. an increase of 2.7 beats/minute with placebo. Mean changes from baseline in standing blood pressure at the end of double-blind treatment ranged from 0.1 to 2.2 mm Hg (systolic) and -0.7 to 2.2 mm Hg (diastolic) for Methylphenidate HCl Extended-Release Tablets and was 1.1 mm Hg (systolic) and -1.8 mm Hg (diastolic) for placebo. In a second placebo-controlled study in adults (Study 5), mean changes from baseline in resting pulse rate were observed for Methylphenidate HCl Extended-Release Tablets and placebo at the end of the double-blind treatment (3.6 and –1.6 beats/minute, respectively). Mean changes from baseline in blood pressure at the end of the double–blind treatment for Methylphenidate HCl Extended-Release Tablets and placebo-treated patients were –1.2 and –0.5 mm Hg (systolic) and 1.1 and 0.4 mm Hg (diastolic), respectively [see Warnings and Precautions].

Post-Marketing Experience

The following additional adverse reactions have been identified during post-approval use of Methylphenidate HCl Extended-Release Tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency:

Blood and Lymphatic System Disorders: Pancytopenia, Thrombocytopenia, Thrombocytopenic purpura

Cardiac Disorders: Angina pectoris, Bradycardia, Extrasystoles, Supraventricular tachycardia, Ventricular extrasystoles

Eye Disorders: Diplopia, Mydriasis, Visual impairment

General Disorders: Chest pain, Chest discomfort, Drug effect decreased, Hyperpyrexia, Therapeutic response decreased

Immune System Disorders: Hypersensitivity reactions such as Angioedema, Anaphylactic reactions, Auricular swelling, Bullous conditions, Exfoliative conditions, Urticarias, Pruritus NEC, Rashes, Eruptions, and Exanthemas NEC

Investigations: Blood alkaline phosphatase increased, Blood bilirubin increased, Hepatic enzyme increased, Platelet count decreased, White blood cell count abnormal

Musculoskeletal, Connective Tissue and Bone Disorders: Arthralgia, Myalgia, Muscle twitching

Nervous System Disorders: Convulsion, Grand mal convulsion, Dyskinesia

Psychiatric Disorders: Disorientation, Hallucination, Hallucination auditory, Hallucination visual, Mania, Logorrhea, Libido changes

Reproductive System and Breast Disorders: Priapism

Skin and Subcutaneous Tissue Disorders: Alopecia, Erythema

Vascular Disorders: Raynaud's phenomenon



REPORTS OF SUSPECTED METHYLPHENIDATE SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Methylphenidate. The information is not vetted and should not be considered as verified clinical evidence.

Possible Methylphenidate side effects / adverse reactions in 10 year old female

Reported by a consumer/non-health professional from United States on 2011-10-06

Patient: 10 year old female weighing 36.3 kg (79.8 pounds)

Reactions: Product Substitution Issue, Vision Blurred

Suspect drug(s):
Methylphenidate



Possible Methylphenidate side effects / adverse reactions in 90 year old female

Reported by a health professional (non-physician/pharmacist) from Belgium on 2011-10-10

Patient: 90 year old female

Reactions: Hypothermia, Coma, General Physical Health Deterioration, Delirium, Death, Hallucination, Visual, Dementia With Lewy Bodies, Attention Deficit/hyperactivity Disorder

Adverse event resulted in: death

Suspect drug(s):
Methylphenidate



Possible Methylphenidate side effects / adverse reactions in 50 year old female

Reported by a individual with unspecified qualification from United States on 2011-10-12

Patient: 50 year old female

Reactions: Pharyngeal Oedema

Suspect drug(s):
Methylphenidate

Other drugs received by patient: Iron



See index of all Methylphenidate side effect reports >>

Drug label data at the top of this Page last updated: 2014-01-15

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