CONCERTA® should not be used in patients being treated (currently or within the preceding 2 weeks) with MAO inhibitors [see Contraindications].
Because of possible increases in blood pressure, CONCERTA® should be used cautiously with vasopressor agents [see Warnings and Precautions].
Coumarin Anticoagulants, Antidepressants, and Selective Serotonin Reuptake Inhibitors
Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (eg, phenobarbital, phenytoin, primidone), and some antidepressants (tricyclics and selective serotonin reuptake inhibitors). Downward dose adjustment of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentrations (or, in the case of coumarin, coagulation times), when initiating or discontinuing concomitant methylphenidate.
Signs and Symptoms
Signs and symptoms of CONCERTA® overdosage, resulting principally from overstimulation of the CNS and from excessive sympathomimetic effects, may include the following: vomiting, agitation, muscle twitching, convulsion, grand mal convulsion, confusional state, hallucinations (auditory and/or visual), hyperhidrosis, headache, pyrexia, tachycardia, palpitations, heart rate increased, sinus arrhythmia, hypertension, mydriasis, and dry mouth.
Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Gastric contents may be evacuated by gastric lavage as indicated. Before performing gastric lavage, control agitation and seizures if present and protect the airway. Other measures to detoxify the gut include administration of activated charcoal and a cathartic. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for pyrexia.
Efficacy of peritoneal dialysis or extracorporeal hemodialysis for CONCERTA® overdosage has not been established.
The prolonged release of methylphenidate from CONCERTA® should be considered when treating patients with overdose.
Poison Control Center
As with the management of all overdosage, the possibility of multiple-drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-to-date information on the management of overdosage with methylphenidate.
Hypersensitivity to Methylphenidate
Hypersensitivity reactions, such as angioedema and anaphylactic reactions, have been observed in patients treated with CONCERTA®. Therefore, CONCERTA® is contraindicated in patients known to be hypersensitive to methylphenidate or other components of the product [see Adverse Reactions].
CONCERTA® is contraindicated in patients with marked anxiety, tension, and agitation, since the drug may aggravate these symptoms.
CONCERTA® is contraindicated in patients with glaucoma.
CONCERTA® is contraindicated in patients with motor tics or with a family history or diagnosis of Tourette's syndrome [see Adverse Reactions].
Monoamine Oxidase Inhibitors
CONCERTA® is contraindicated during treatment with monoamine oxidase (MAO) inhibitors, and also within a minimum of 14 days following discontinuation of a MAO inhibitor (hypertensive crises may result) [see Drug Interactions].
DRUG ABUSE AND DEPENDENCE
Methylphenidate is a Schedule II controlled substance under the Controlled Substances Act.
As noted in the Box Warning, CONCERTA® should be given cautiously to patients with a history of drug dependence or alcoholism. Chronic 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.
In two placebo-controlled human abuse potential studies, single oral doses of CONCERTA® were compared to single oral doses of immediate-release methylphenidate (IR MPH) and placebo in subjects with a history of recreational stimulant use to assess relative abuse potential. For the purpose of this assessment, the response for each of the subjective measures was defined as the maximum effect within the first 8 hours after dose administration.
In one study (n=40), both CONCERTA® (108 mg) and 60 mg IR MPH compared to placebo produced statistically significantly greater responses on the five subjective measures suggestive of abuse potential. In comparisons between the two active treatments, however, CONCERTA® (108 mg) produced variable responses on positive subjective measures that were either statistically indistinguishable from (Abuse Potential, Drug Liking, Amphetamine, and Morphine Benzedrine Group [Euphoria]) or statistically less than (Stimulation – Euphoria) responses produced by 60 mg IR MPH.
In another study (n=49), both doses of CONCERTA® (54 mg and 108 mg) and both doses of IR MPH (50 mg and 90 mg) produced statistically significantly greater responses compared to placebo on the two primary scales used in the study (Drug Liking, Euphoria). When doses of CONCERTA® (54 mg and 108 mg) were compared to IR MPH (50 mg and 90 mg), respectively, CONCERTA® produced statistically significantly lower subjective responses on these two scales than IR MPH. CONCERTA® (108 mg) produced responses that were statistically indistinguishable from the responses on these two scales produced by IR MPH (50 mg). Differences in subjective responses to the respective doses should be considered in the context that only 22% of the total amount of methylphenidate in CONCERTA® tablets is available for immediate release from the drug overcoat [see System Components and Performance
Although these findings reveal a relatively lower response to CONCERTA® on subjective measures suggestive of abuse potential compared to IR MPH at roughly equivalent total MPH doses, the relevance of these findings to the abuse potential of CONCERTA® in the community is unknown.
As noted in the Box Warning, careful supervision is required during withdrawal from abusive use since severe depression may occur. Withdrawal following chronic therapeutic use may unmask symptoms of the underlying disorder that may require follow-up.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994.
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