Side Effects of Quillivant XR (methylphenidate hydrochloride)

Quillivant XR (methylphenidate hydrochloride) is a central nervous system (CNS or brain) stimulant used to treat attention deficit hyperactivity disorder (ADHD). It stimulates the CNS in a manner similar to amphetamines; however, its actions are milder than amphetamines.

Amphetamines stimulate the brain by increasing the level of neurotransmitters, dopamine and norepinephrine, in the brain (neurotransmitters are chemicals produced by nerves that are released and attach to other nearby nerves as a means of communication among nerves).

The exact mechanism of action of Quillivant XR in people with ADHD is unknown. Methylphenidate is the active ingredient in Ritalin and Concerta and is also available as pills and in a patch. 

Common side effects of Quillivant XR include

• decreased appetite,
• sleeplessness,
• allergic contact dermatitis,
• nausea,
• vomiting,
• weight loss,
• dizziness,
• abdominal pain, and
• emotional instability.

Serious side effects of Quillivant XR include abuse. Long term abuse of Quillivant XR can cause tolerance, psychological dependence, abnormal behavior, and psychosis.

Drug interactions of Quillivant XR include monoamine oxidase inhibitors (MAOIs) because of risks of hypertensive crisis.

There are no adequate studies done on Quillivant XR to determine safe and effective use in pregnant women.

It is unknown if Quillivant XR enters breast milk; therefore, it is best to be cautious before using it in breastfeeding mothers.

Side effects of methylphenidate are

• decreased appetite,
• sleeplessness,
• allergic contact dermatitis,
• nausea,
• vomiting,
• weight loss,
• dizziness,
• abdominal pain,
• emotional instability and
• anorexia.

Methylphenidate may be abused and it is a Schedule II controlled medication. Long term abuse can cause tolerance, psychological dependence, abnormal behavior, and psychosis. Use cautiously in people with a history of drug or alcohol abuse.

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

• Known hypersensitivity to methylphenidate products or other ingredients of Quillivant 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

Clinical 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.

Clinical Trials Experience 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:

• 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 Quillivant XR In Children And Adolescents With ADHD

There is limited experience with Quillivant XR in controlled trials. Based on this limited experience, the adverse reaction profile of Quillivant XR appears similar to other methylphenidate extended-release products. The most common (≥2% in the Quillivant XR group and greater than placebo) adverse reactions reported in the Phase 3 controlled study conducted in 45 ADHD patients (ages 6–12 years) were

• affect lability,
• excoriation,
• initial insomnia,
• tic,
• decreased appetite,
• vomiting,
• motion sickness,
• eye pain, and
• rash.

Table 2: Common Adverse Reactions occurring in ≥2% of subjects on Quillivant XR and greater than placebo during the controlled cross-over phase

Postmarketing 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: Severe hepatocellular injury

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: 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, Mania

Urogenital System: Priapism

Skin and Subcutaneous Tissue Disorders: Alopecia, Erythema

Vascular Disorders: Raynaud's phenomenon

Clinically Important Drug Interactions

MAO Inhibitors

Do not administer Quillivant XR concomitantly with monoamine oxidase inhibitors (MAOIs) or within 14 days after discontinuing MAOI treatment. Concomitant use of MAOIs and CNS stimulants can cause hypertensive crisis.

Potential outcomes include

• death,
• stroke,
• myocardial infarction,
• aortic dissection,
• ophthalmological complications,
• eclampsia,
• pulmonary edema, and
• renal failure.

Drug Abuse And Dependence

Controlled Substance

Quillivant XR contains methylphenidate, a Schedule II controlled substance.

Abuse

CNS stimulants including Quillivant XR, other methylphenidate-containing products, and amphetamines have a high potential for abuse. Abuse is characterized by

• impaired control over drug use,
• compulsive use,
• continued use despite harm, and
• craving.

Signs and symptoms of CNS stimulant abuse include

• increased heart rate,
• respiratory rate,
• blood pressure, and/or sweating,
• dilated pupils,
• hyperactivity,
• restlessness,
• insomnia,
• decreased appetite,
• loss of coordination,
• tremors,
• flushed skin,
• vomiting, and/or abdominal pain.

Anxiety, psychosis, hostility, aggression, suicidal or homicidal ideation have also been observed.  Abusers of CNS stimulants may chew, snort, inject, or use other unapproved routes of administration which can result in overdose and death.

To reduce the abuse of CNS stimulants including Quillivant XR, assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and on proper storage and disposal of CNS stimulants, monitor for signs of abuse while on therapy, and re-evaluate the need for Quillivant XR use.

Dependence

Tolerance

Tolerance (a state of adaptation in which exposure to a drug results in a reduction of the drug's desired and/or undesired effects over time) can occur during chronic therapy with CNS stimulants including Quillivant XR.

Dependence

Physical dependence (a state of adaptation manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist) can occur in patients treated with CNS stimulants including Quillivant XR.

Withdrawal symptoms after abrupt cessation following prolonged high-dosage administration of CNS stimulants include

• dysphoric mood;
• fatigue;
• vivid, unpleasant dreams;
• insomnia or hypersomnia;
• increased appetite; and
• psychomotor retardation or agitation.