Methylphenidate

CNS stimulant use has been associated with serious cardiovascular events (eg, sudden death, arrhythmia, and myocardial infarction in children and adolescents; sudden death, stroke, and myocardial infarction in adults) in patients with and without preexisting structural cardiac abnormalities or other serious heart problems (Shin 2016). These products should be avoided in patients with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that could further increase their risk of sudden death. Patients should be carefully evaluated for cardiac disease prior to initiation of therapy. Some products are contraindicated in patients with heart failure, arrhythmias or recent MI.

Transdermal system may cause a persistent loss of skin pigmentation at and around the application site, as well as at distant sites from the application site; loss of skin pigmentation may continue after discontinuation of transdermal system. May resemble vitiligo especially if loss of skin pigmentation occurs at areas distant from application site; use with caution in patients with a history and/or family history of vitiligo. Monitor for signs of skin depigmentation; immediately discontinue use if patient experiences chemical leukoderma.

Hypersensitivity reactions, such as angioedema and anaphylactic reactions have been reported.

Stimulants are associated with peripheral vasculopathy, including Raynaud phenomenon; signs/symptoms are usually mild and intermittent, and generally improve with dose reduction or discontinuation. Digital ulceration and/or soft tissue breakdown have been observed rarely; monitor for digital changes during therapy and seek further evaluation (eg, rheumatology) if necessary.

Prolonged and painful erections (priapism), sometimes requiring surgical intervention, have been reported (rarely) with methylphenidate and atomoxetine use in pediatric and adult patients. Priapism has been reported to develop after some time on the drug, often subsequent to an increase in dose but also during a period of drug withdrawal (drug holidays or discontinuation). Patients with certain hematological dyscrasias (eg, sickle cell disease), malignancies, perineal trauma, or concomitant use of alcohol, illicit drugs, or other medications associated with priapism may be at increased risk. Patients who develop abnormally sustained or frequent and painful erections should discontinue therapy and seek immediate medical attention. An emergent urological consultation should be obtained in severe cases. Priapism has been associated with different dosage forms and products; it is not known if rechallenge with a different formulation will risk recurrence. Avoidance of stimulants and atomoxetine may be preferred in patients with severe cases that were slow to resolve and/or required detumescence (Eiland 2014).

Difficulty in accommodation and blurred vision have been reported with the use of stimulants. Disease-related concerns:

CNS stimulants, including methylphenidate-containing products and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Long-term abusive use can lead to marked tolerance and psychological dependence with varying degrees of abnormal behavior. Frank psychotic episodes can occur, especially with parenteral abuse. Careful supervision is required during withdrawal from abusive use because severe depression may occur. Withdrawal following long-term therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.

Use with caution in patients with hypertension and other cardiovascular conditions that might be exacerbated by increases in blood pressure or heart rate. Some products are contraindicated in patients with severe hypertension, hyperthyroidism or angina.

Use with caution in patients with pre-existing psychosis or bipolar disorder (may induce mixed/manic episode). May exacerbate symptoms of behavior and thought disorder in psychotic patients; new-onset psychosis or mania may occur with stimulant use. Patients should be screened for bipolar disorder prior to treatment; consider discontinuation if such symptoms (eg, delusional thinking, hallucinations, mania) occur. May be associated with aggressive behavior or hostility (causal relationship not established); monitor for development or worsening of these behaviors. Suicidal ideation, attempts, and very rarely, completed suicide have been reported. Monitor for suicide-related behavior.

Use with caution in patients with a history of seizure disorder; may lower seizure threshold leading to new onset or breakthrough seizure activity.

Use with caution in patients with Tourette syndrome or other tic disorders. Stimulants may exacerbate tics (motor and phonic) and Tourette syndrome; however, evidence demonstrating increased tics is limited. Evaluate for tics and Tourette syndrome prior to therapy initiation; use is contraindicated with some products (AACAP [Murphy 2013; Pliszka 2007]). Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Appetite suppression may occur, particularly in children. Use of stimulants has been associated with weight loss and slowing of growth rate; monitor growth rate and weight during treatment. Treatment interruption may be necessary in patients who are not increasing in height or gaining weight as expected. Dosage form specific issues:

Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.

Controlled-release capsules are not interchangeable with other controlled-release formulations.

Should not be used with preexisting severe gastrointestinal narrowing conditions, such as esophageal motility disorders, small bowel disease, “short” gut syndrome, cystic fibrosis, history of peritonitis, chronic intestinal pseudo-obstruction, or Meckel diverticulum.

Transdermal system may cause allergic contact sensitization, characterized by intense local reactions (eg, edema, papules) that may spread beyond the patch site; sensitization may subsequently manifest systemically with other routes of methylphenidate administration; monitor closely. Avoid exposure of application site to any direct external heat sources (eg, hair dryers, heating pads, electric blankets); may increase the rate and extent of absorption and risk of overdose. Efficacy of therapy for >7 weeks has not been established.

Some dosage forms may contain lactose or sucrose; use with caution in patients intolerant to either component (some manufacturer labels recommend avoiding use in such patients).

Concomitant use with halogenated anesthetics is contraindicated; may cause sudden elevations in blood pressure; if surgery is planned, do not administer Metadate CD on the day of surgery.

Some dosage forms contain phenylalanine, which can be harmful to patients with phenylketonuria (PKU). Before prescribing, consider the combined daily amount of phenylalanine from all sources. Other warnings/precautions:

Appropriate use: Recommended to be used as part of a comprehensive treatment program for attention deficit disorders.