Methylphenidate Hydrochloride Tablets, USP
Methylphenidate Hydrochloride Extended-release Tablets, USP
Methylphenidate hydrochloride is a mild central nervous system (CNS) stimulant. Methylphenidate hydrochloride is available as 5, 10, and 20 mg tablets for oral administration. A 20 mg extended-release tablet for oral administration is also available. Methylphenidate hydrochloride is methyl a-phenyl-2-piperi-dineeacetate hydrochloride.

Methylphenidate hydrochloride is a white, odorless, fine crystalline powder. Its solutions are acid to litmus. It is freely soluble in water and in methanol, soluble in alcohol, and sliglhtly soluble in chloroform and in acetone. Its molecular weight is 269.77.

Inactive Ingredients: Methylphenidate hydrochloride tablets; lactose, magnesium stearate, microcrystalline cellulose, sodium starch glycolate; 5 mg contains D&C Yellow #10; 10 mg contains FD&C Green #3, and 20 mg contains FD&C Yellow #6.

Methylphenidate hydrochloride extended-release tablets: cetyl alcohol, ethylcellulose, lactose and magnesium stearate.

INDICATIONS

Attention Deficit Disorders, Narcolepsy: Attention Deficit Disorders (previously known as Minimal Brain Dysfunction in Children).

Other terms being used to describe the behavioral syndrome below include: Hyperkinetic Child Syndrome, Minimal Brain Damage, Minimal Cerebral Dysfunction, Minor Cerebral Dysfunction.

Methylphenidate hydrochloride is indicated as an integral proof of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms; moderate-to-severe distractibility, short attention span, hyperactivity, emotional lability and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted.

Special Diagnostic Considerations: Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources.

Characteristics commonly reported include: Chronic history of short attention span, distractibility, emotional lability, impulsivity, and moderate-to-severe hyperactivity; minor neurological signs and abnormal EEG. Learning may or may not be impaired.The diagnosis must be based upon a complete history and evaluation of the child and not solely on the presence of one or more of these characteristics.

Drug treatment is not indicated for all children with this syndrome. Stimulants are not intended for use in the child who exhibits symptoms secondary to environmental factors and/or primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial-intervention is generally necessary. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician's assessment of the chronicity and severity of the child's symptoms.

DOSAGE AND ADMINISTRATION

Dosage should be individualized according to the needs and responses of the patient.

Adult

Tablets: Administer in divided doses 2 or 3 times daily, preferably 30 to 45 minutes before meals. Average dosage is 20 to 30 mg daily. Some patients may require 40 to 60 mg daily. In others, 10 to 15 mg daily will be adequate. Patients who are unable to sleep if medication is taken late in the day should take the last dose before 6 p.m..

Extended-Release Tablets: Methylphenidate hydrochloride extended-release tablets have a duration of action of approximately 8 hours. Therefore, the extended-release tablets may be used in place of the immediate-release tablets when the 8-hour dosage of methylphenidate hydrochloride extended-release tablets corresponds to the titrated 8-hour dosage of the immediate-release tablets. Methylphenidate hydrochloride extended-release tablets must be swallowed whole and never crushed or chewed.

Children (6 years and over)

Methylphenidate hydrochloride should be initiated in small doses, with gradual weekly increments. Daily dosage above 60 mg is not recommended.

If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.

Tablets: Start with 5 mg twice daily (before breakfast and lunch) with gradual increments of 5 to 10 mg weekly.

Extended-Release Tablets: Methylphenidale hydrochloride extended-release tablets have a duration of action of approximately 8 hours. Therefore, the extended-release tablets may be used in place of the immediate-release tablets when the 8-hour dosage of methylphenidate hydrochloride extended-release tablets corresponds to the titrated 8-hour dosage of the immediate-release tablets. Methylphenidate hydrochloride extended-release tablets must be swallowed whole and never crushed or chewed.

If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage, or, if necessary, discontinue the drug.

Methylphenidate should be periodically discontinued to assess the child's condition. Improvement may be sustained when the drug is either temporarily or permanently discontinued.

Drug treatment should not and need not be indefinite and usually may be discontinued after puberty.

HOW SUPPLIED

Methylphenidate hydrochloride tablets are supplied as-

Tablets, 5 mg: Round, yellow, uncoated, unscored, (debossed 531 and MD) in bottles of 100 and 1,000.
Tablets, 10 mg: Round, pale blue/green, uncoated, scored, (debossed 530 and MD) in bottles of 100 and 1,000.
Tablets, 20 mg: Round, orange, uncoated, scored, (debossed 532 and MD) in bottles of 100 and 1,000.
Extended-release Tablets, 20 mg: Round, white, uncoated, unscored, (debossed 562 and MD) in bottles of 100.
NOTE: Extended-release tablets are color-additive free.

PHARMACIST: Dispense in a tight light-resistant container as defined in the USP with a child-resistant closure.

Store at controlled room temperature 15°-30°C (59°-86°F). Protect from moisture.

WARNINGS

Methylphenidate should not be used in children under six years, since safety and efficacy in this age group have not been established.

Sufficient data on safety and efficacy of long-term use of methylphenidate hydrochloride in children are not yet available. Although a causal relationship has not been established, suppression of growth ( i.e., weight gain, and/or height) has been reported with the long-term use of stimulants in children. Therefore, patients requiring long-term therapy should be carefully monitored. Methylphenidate should not be used for severe depression of either exogenous or endogenous origin. Clinical experience suggests that in psychotic children, administration of methylphenidate may exacerbate symptoms of behavior disturbance and thought disorder
Methylphenidals should not be used for the prevention or treatment of normal fatigue states. There is some clinical evidence that methylphenidate may lower the convulsive threshold in patients with prior history of seizures, with prior EEG abnormalities in absence of seizures, and very rarely, in absence of history of seizures and no prior EEG evidence of seizures. Safe concomitant use of anticonvulsants and methylphenidate has not been established. In the presence of seizures, the drug should be discontinued. Use cautiously in patients with hypertension. Blood pressure should be monitored at appropriate intervals in all patients taking methylphenidate, especially those with hypertension.

Symptoms of visual disturbances have been encountered in rare cases. Difficulties with accommodation and blurring of vision have been reported.

Drug Interactions

Methylphenidate may decrease the hypotensive effect of guanethidine. Use cautiously with pressor agents and MAO inhibitors. Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (phenobarbital, phenytoin, primidone), phenylbutazone, and tricyclic anti-depressants (imipramine, clomipramnine, desipramine). Downward dosage adjustments of these drugs may be required when given concomitantly with methylphenidate.

Usage In Pregnancy

Adequate animal reproduction studies to establish safe use of methylphenidate during pregnancy have not been conducted. Therefore, until more information is available, methylphenidate hydrochloride should not be prescribed for women of childbearing age unless, in the opinion of the physician, the potential benefits outweigh the possible risks.

PRECAUTIONS

Patients with an element of agitation may react adversely; discontinue therapy if necessary. Periodic C.C. 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 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 is usually not indicated.

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

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.

Methylphenlidate did not cause any increases 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 vitro assay.