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Ritalin Package Insert
T2001-08 89002403
Ritalin® hydrochloride methylphenidate hydrochloride
tablets USP
Ritalin-SR
methylphenidate hydrochloride USP sustained-release tablets Rx only
Prescribing Information
DESCRIPTION
Ritalin hydrochloride, methylphenidate hydrochloride USP, is a mild central
nervous system (CNS) stimulant, available as tablets of 5, 10, and 20 mg for
oral administration; Ritalin-SR is available as sustained-release tablets of 20
mg for oral administration. Methylphenidate hydrochloride is methyl
á-phenyl-2-piperidineacetate hydrochloride, and its structural formula is
Methylphenidate hydrochloride USP 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 slightly soluble in chloroform and in
acetone. Its molecular weight is 269.77. Inactive Ingredients. Ritalin tablets:
D&C Yellow No. 10 (5-mg and 20-mg tablets), FD&C Green No. 3 (10-mg tablets),
lactose, magnesium stearate, polyethylene glycol, starch (5-mg and 10-mg
tablets), sucrose, talc, and tragacanth (20-mg tablets). Ritalin-SR tablets:
Cellulose compounds, cetostearyl alcohol, lactose, magnesium stearate, mineral
oil, povidone, titanium dioxide, and zein.
CLINICAL PHARMACOLOGY
Ritalin is a mild central nervous system stimulant. The mode of action in man
is not completely understood, but Ritalin presumably activates the brain stem
arousal system and cortex to produce its stimulant effect. There is neither
specific evidence which clearly establishes the mechanism whereby Ritalin
produces its mental and behavioral effects in children, nor conclusive evidence
regarding how these effects relate to the condition of the central nervous
system. Ritalin in the SR tablets is more slowly but as extensively absorbed as
in the regular tablets. Relative bioavailability of the SR tablet compared to
the Ritalin tablet, measured by the urinary excretion of Ritalin major
metabolite (á-phenyl-2-piperidine acetic acid) was 105% (49%-168%) in children
and 101% (85%-152%) in adults. The time to peak rate in children was 4.7 hours
(1.3-8.2 hours) for the SR tablets and 1.9 hours (0.3-4.4 hours) for the
tablets. An average of 67% of SR tablet dose was excreted in children as
compared to 86% in adults. In a clinical study involving adult subjects who
received SR tablets, plasma concentrations of Ritalin’s major metabolite
appeared to be greater in females than in males. No gender differences were
observed for Ritalin plasma concentration in the same subjects.
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. Ritalin is indicated as an integral
part 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.
CONTRAINDICATIONS
Marked anxiety, tension, and agitation are contraindications to Ritalin, since
the drug may aggravate these symptoms. Ritalin is contraindicated also in
patients known to be hypersensitive to the drug, in patients with glaucoma, and
in patients with motor tics or with a family history or diagnosis of
Tourette’s syndrome. Ritalin is contraindicated during treatment with
monoamine oxidase inhibitors, and also within a minimum of 14 days following
discontinuation of a monoamine oxidase inhibitor (hypertensive crises may
result).
WARNINGS
Ritalin 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 Ritalin 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. Ritalin should not be used for severe depression of
either exogenous or endogenous origin. Clinical experience suggests that in
psychotic children, administration of Ritalin may exacerbate symptoms of
behavior disturbance and thought disorder. Ritalin should not be used for the
prevention or treatment of normal fatigue states. There is some clinical
evidence that Ritalin 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 Ritalin 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 Ritalin, 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
Ritalin may decrease the hypotensive effect of guanethidine. Use cautiously
with pressor agents. Human pharmacologic studies have shown that Ritalin 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 Ritalin. Serious
adverse events have been reported in concomitant use with clonidine, although
no causality for the combination has been established. The safety of using
methylphenidate in combination with clonidine or other centrally acting alpha-2
agonists has not been systemically evaluated.
Usage in Pregnancy
Adequate animal reproduction studies to establish safe use of Ritalin 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, Ritalin should not be prescribed for women
of childbearing age unless, in the opinion of the physician, the potential
benefits outweigh the possible risks.
Drug Dependence
Ritalin should be given cautiously to emotionally unstable patients, such as
those with a istory of drug dependence or alcoholism, because such patients may
increase dosage on their own initiative. Chronically abusive use can lead to
marked tolerance and psychic dependence with varying degrees of abnormal
behavior. Frank psychotic episodes can occur, especially with parenteral abuse.
Careful supervision is required during drug withdrawal, since severe depression
as well as the effects of chronic overactivity can be unmasked. Long-term
follow-up may be required because of the patient’s basic personality
disturbances.
PRECAUTIONS
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 Ritalin 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 Ritalin is usually not indicated. Long-term effects
of Ritalin in children have not been well established.
Carcinogenesis/Mutagenesis
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 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 vivo assay.
ADVERSE REACTIONS
Nervousness and insomnia are the most common adverse reactions but are usually
controlled by reducing dosage and omitting the drug in the afternoon or
evening. Other reactions include hypersensitivity (including skin rash,
urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with
histopathological findings of necrotizing vasculitis, and thrombocytopenic
purpura); anorexia; nausea; dizziness; palpitations; headache; dyskinesia;
drowsiness; blood pressure and pulse changes, both up and down; tachycardia;
angina; cardiac arrhythmia; abdominal pain; weight loss during prolonged
therapy. There have been rare reports of Tourette’s syndrome. Toxic psychosis
has been reported. Although a definite causal relationship has not been
established, the following have been reported in patients taking this drug:
instances of abnormal liver function, ranging from transaminase elevation to
hepatic coma; isolated cases of cerebral arteritis and/or occlusion; leukopenia
and/or anemia; transient depressed mood; a few instances of scalp hair loss.
Very rare reports of neuroleptic malignant syndrome (NMS) have been received,
and, in most of these, patients were concurrently receiving therapies
associated with NMS. In a single report, a ten year old boy who had been taking
methylphenidate for approximately 18 months experienced an NMS-like event
within 45 minutes of ingesting his first dose of venlafaxine. It is uncertain
whether this case represented a drug-drug interaction, a response to either
drug alone, or some other cause. In children, loss of appetite, abdominal pain,
weight loss during prolonged therapy, insomnia, and tachycardia may occur more
frequently; however, any of the other adverse reactions listed above may also
occur.
DOSAGE AND ADMINISTRATION
Dosage should be individualized according to the needs and responses of the
patient.
Adults
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. SR Tablets: Ritalin-SR tablets have a duration
of action of approximately 8 hours. Therefore, Ritalin-SR tablets may be used
in place of Ritalin tablets when the 8-hour dosage of Ritalin-SR corresponds to
the titrated 8-hour dosage of Ritalin. Ritalin-SR tablets must be swallowed
whole and never crushed or chewed.
Children (6 years and over)
Ritalin 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. SR Tablets: Ritalin-SR tablets
have a duration of action of approximately 8 hours. Therefore, Ritalin-SR
tablets may be used in place of Ritalin tablets when the 8-hour dosage of
Ritalin-SR corresponds to the titrated 8-hour dosage of Ritalin. Ritalin-SR
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. Ritalin 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.
OVERDOSAGE
Signs and symptoms of acute overdosage, resulting principally from
overstimulation of the central nervous system and from excessive
sympathomimetic effects, may include the following: vomiting, agitation,
tremors, hyperreflexia, muscle twitching, convulsions (may be followed by
coma), euphoria, confusion, hallucinations, delirium, sweating, flushing,
headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias,
hypertension, mydriasis, and dryness of mucous membranes. Page 7 Consult with a
Certified Poison Control Center regarding treatment for up-to-date guidance and
advice. 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. In the presence of severe intoxication, use a carefully
titrated dosage of a short-acting barbiturate before performing gastric lavage.
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 hyperpyrexia. Efficacy of peritoneal dialysis or extracorporeal
hemodialysis for Ritalin overdosage has not been established.
HOW SUPPLIED
Tablets 5 mg — round, yellow (imprinted CIBA 7)
Bottles of
100.......................................................................
...........NDC 0083-0007-30
Tablets 10 mg — round, pale green, scored (imprinted CIBA 3)
Bottles of
100.......................................................................
...........NDC 0083-0003-30
Tablets 20 mg — round, pale yellow, scored (imprinted CIBA 34)
Bottles of 100
...........................................................................
.......NDC 0083-0034-30
Do not store above 30°C (86°F). Protect from light.
Dispense in tight, light-resistant container (USP).
SR Tablets 20 mg — round, white, coated (imprinted CIBA 16)
Bottles of
100.......................................................................
...........NDC 0083-0016-30
Note : SR Tablets are color-additive free euticals Corporation
East Hanover, New Jersey 07936
© 2001 Novartis
Note:
The following URL is the FDA posted Ritalin drug insert. The FDA website
requires the document to be viewed in .PDF format and is available for viewing
only if your PC is equipped with Adobe Acrobat Reader.
http://www.fda.gov/cder/foi/label/2002/18029slr032lbl.pdf
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