PRECAUTIONS

General

Patients with an element of agitation may react adversely; discontinue therapy if necessary.

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

Drug treatment is not indicated in all cases of this behavioral syndrome and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe methylphenidate hydrochloride should depend on the physician's assessment of the chronicity and severity of the child's symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics.

When these symptoms are associated with acute stress reactions, treatment with methylphenidate hydrochloride is usually not indicated.

Long-term effects of methylphenidate hydrochloride in children have not been well established.

Information for Patients

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Abuse, Misuse, and Addiction
Educate patients and their families about the risks of abuse, misuse, and addiction of Methylphenidate Hydrochloride Chewable Tablets, which can lead to overdose and death, and proper disposal of any unused drug (see WARNINGSand**PRECAUTIONS****,**DRUG ABUSE AND DEPENDENCE, OVERDOSAGE). Advise patients to store Methylphenidate Hydrochloride Chewable Tablets in a safe place, preferably locked, and instruct patients to not give Methylphenidate Hydrochloride Chewable Tablets to anyone else.

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** Risks to Patients with Serious Cardiac Disease**
Advise patients that there are potential risks to patients with serious cardiac disease, including sudden death, with Methylphenidate Hydrochloride Chewable Tablets use. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease (see WARNINGS).

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** Increased Blood Pressure and Heart Rate**
Advise patients that Methylphenidate Hydrochloride Chewable Tablets can elevate blood pressure and heart rate (see WARNINGS).

Psychiatric Adverse Reactions
Advise patients that Methylphenidate Hydrochloride Chewable Tablets, at recommended doses, can cause psychotic or manic symptoms, even in patients without a prior history of psychotic symptoms or mania (see WARNINGS).

Priapism
Advise patients, caregivers, and family members of the possibility of painful or prolonged penile erections (priapism).Instruct the patient to seek immediate medical attention in the event of priapism.

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** Circulation Problems in Fingers and Toes [Peripheral Vasculopathy, Including Raynaud's Phenomenon]**

• Instruct patients beginning treatment with methylphenidate hydrochloride about the risk of peripheral vasculopathy, including Raynaud's Phenomenon, and associated signs and symptoms; fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.
• Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. *Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking methylphenidate hydrochloride.
• Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Suppression of Growth in Pediatric Patients

Advise patients, caregivers, and family members that Methylphenidate Hydrochloride Chewable Tablets can cause slowing of growth and weight loss (see Warnings).

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** Increased Intraocular Pressure and Glaucoma**

Advise patients that IOP and glaucoma may occur during treatment with Methylphenidate Hydrochloride Chewable Tablets (see Warnings).

Motor and Verbal Tics, and Worsening of Tourette’s Syndrome

Advise patients that motor and verbal tics and worsening of Tourette’s Syndrome may occur during treatment with Methylphenidate Hydrochloride Chewable Tablets.Instructthe patients to notify their healthcare provider if emergence or worsening of tics or Tourette’s syndrome occurs (see WARNINGS).

Choking– Taking this product without adequate fluid may cause it to swell and block your throat or esophagus and may cause choking. Do not take this product if you have difficulty in swallowing. If you experience chest pain, vomiting, or difficulty in swallowing or breathing after taking this product, seek immediate medical attention.

Directions– Take this product (child or adult dose) with at least 8 ounces (a full glass) of water or other fluid. Taking this product without enough liquid may cause choking. See choking warning.

Drug Interactions

Monoamine Oxidase Inhibitors (MAOI)
Concomitant use of MAOIs and CNS stimulants, including methylphenidate hydrochloride can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure (seeCONTRAINDICATIONS). Concomitant use of Methylphenidate hydrochloride with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated.

Antihypertensive Drugs
Methylphenidate hydrochloride may decrease the effectiveness of drugs used to treat hypertension. Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed.

Risperidone
Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS). Monitor for signs of EPS.

Methylphenidate hydrochloride may decrease the hypotensive effect of guanethidine. Use cautiously with pressor agents.

Human pharmacologic studies have shown that methylphenidate hydrochloride may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (phenobarbital, diphenylhydantoin, primidone), phenylbutazone, and tricyclic drugs (imipramine, clomipramine, desipramine). Downward dosage adjustments of these drugs may be required when given concomitantly with methylphenidate hydrochloride.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In a lifetime carcinogenicity study carried out in B6C3F1 mice, methylphenidate caused an increase in hepatocellular adenomas and, in males only, an increase in hepatoblastomas, at a daily dose of approximately 60 mg/kg/day. This dose is approximately 30 times and 2.5 times the maximum recommended human dose on a mg/kg and mg/m2 basis, respectively. Hepatoblastoma is a relatively rare rodent malignant tumor type. There was no increase in total malignant hepatic tumors. The mouse strain used is sensitive to the development of hepatic tumors, and the significance of these results to humans is unknown.

Methylphenidate did not cause any increase in tumors in a lifetime carcinogenicity study carried out in F344 rats; the highest dose used was approximately 45 mg/kg/day, which is approximately 22 times and 4 times the maximum recommended human dose on a mg/kg and mg/m2 basis, respectively.

Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or in the in vitro mouse lymphoma cell forward mutation assay. Sister chromatid exchanges and chromosome aberrations were increased, indicative of a weak clastogenic response, in an in vitro assay in cultured Chinese Hamster Ovary (CHO) cells. The genotoxic potential of methylphenidate has not been evaluated in an in vivo assay.

Usage in Pregnancy

Adequate animal reproduction studies to establish safe use of methylphenidate hydrochloride during pregnancy have not been conducted. However, in a recently conducted study, methylphenidate has been shown to have teratogenic effects in rabbits when given in doses of 200 mg/kg/day, which is approximately 167 times and 78 times the maximum recommended human dose on a mg/kg and a mg/m2 basis, respectively. In rats, teratogenic effects were not seen when the drug was given in doses of 75 mg/kg/day, which is approximately 62.5 and 13.5 times the maximum recommended human dose on a mg/kg and a mg/m2 basis, respectively. Therefore, until more information is available, methylphenidate should not be prescribed for women of childbearing age unless, in the opinion of the physician, the potential benefits outweigh the possible risks.