Methylphenidate

Brand Name: Ritalin

outside U.S., Brand Names also known as: Centedrin; Rilatine; Rubifen

Description

Methylphenidate is a central nervous system (CNS) stimulant used to treat narcolepsy (sudden and uncontrollable attacks of drowsiness and sleep) and attention-deficit hyperactivity disorder (ADHD).

Methylphenidate works by increasing attention and decreasing restlessness in children and adults who are overactive, cannot concentrate for very long or are easily distracted, and are impulsive. This medicine is used as part of a total treatment program that also includes social, educational, and psychological treatment.

Pharmacology

Methylphenidate is a mild central nervous system stimulant.

The mode of action in humans is not completely understood, but Methylphenidate 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 Methylphenidate produces its mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.

Peak plasma concentrations of 10.8 and 7.8 ng/mL were observed, on average, 2 hours after administration of 0.30 mg/kg in children and adults, respectively.

Indications and Usage

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.

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 ability, 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.

Narcolepsy.

Contraindications

Marked anxiety, tension, and agitation are contraindications to Methylphenidate, since the drug may aggravate these symptoms. Methylphenidate 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.

Warnings

Children 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 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.

Methylphenidate should not be used for the prevention or treatment of normal fatigue states.

Seizures: 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.

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 Methylphenidate HCl 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.

Pregnancy & Nursing: Methylphenidate should not be prescribed for women of childbearing age unless, in the opinion of the physician, the potential benefits outweigh the possible risks.

Interference with Cognitive or Motor Performance: Since any psychoactive medication may impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Methylphenidate therapy does not adversely affect their ability to engage in such activities.

Drug Interactions

Methylphenidate may decrease the hypotensive effect of guanethidine. Use cautiously with presser agents and MAO inhibitors.

Human pharmacologic studies have shown that Methylphenidate 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.

BEFORE USING THIS MEDICINE: INFORM YOUR DOCTOR OR PHARMACIST of all prescription and over-the-counter medicine that you are taking, especially MAO inhibitors, other CNS stimulants, or pimozide; have any other medical problems, especially Gilles de la Tourette's syndrome (or any other tics), glaucoma, high blood pressure, or severe anxiety, tension, or depression; are now using or have used cocaine. Inform your doctor of any other medical conditions including anxiety, glaucoma, allergies, pregnancy, or breast-feeding.

TO PREVENT THIS MEDICINE FROM AFFECTING SLEEP: try not to take a dose later than 6 pm.

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 multiform 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: isolated cases of cerebral arthritis and/or occlusion; leucopoenia and/or anemia; transient depressed mood; a few instances of scalp hair loss.

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.

Drug Abuse and Dependence:

Methylphenidate should be given cautiously to emotionally unstable patients, such as those with a history 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 parental abuse. Careful supervision is required during drug withdrawal, since severe depression as well as the effects of chronic over activity can be unmasked. Long-term follow-up may be required because of the patient's basic personality disturbances.

Overdose

Signs and Symptoms

Signs and symptoms of acute overdosage, resulting principally from over stimulation 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.

Treatment

If you or someone you know may have used more than the recommended dose of this medicine, contact your local poison control center or emergency room immediately.

Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate over stimulation already present. If signs and symptoms are not too severe and the patient is conscious, gastric contents may be evacuated by induction of emesis or gastric lavage. In the presence of severe intoxication, use a carefully titrated dosage of a short- acting barbiturate before performing gastric lavage.

Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for hyperpyrexia.

Dosage

Do not exceed the recommended dosage or take this medicine for longer than prescribed. Do not stop taking this medicine without checking with your doctor. Keep all doctor and laboratory appointments while you are using this medicine.

Follow the directions for using this medicine provided by your doctor.
CHILDREN: Take your dose exactly at the times indicated by your doctor. ADULTS: Take your dose 30 to 45 minutes before meals unless directed otherwise by your doctor. TO PREVENT THIS MEDICINE FROM AFFECTING SLEEP: try not to take a dose later than 6 pm.
Store this medicine at room temperature, in a tightly-closed container, away from heat and light.
If you miss a dose of this medicine, take it as soon as possible. Take the remaining doses for the day at evenly spaced intervals. Do not take 2 doses at once.

Additional Information: Do not share this medicine with others for whom it was not prescribed. Do not use this medicine for other health conditions. Keep this medicine out of the reach of children.

IF YOU WILL BE USING THIS MEDICINE FOR AN EXTENDED PERIOD OF TIME, be sure to obtain necessary refills before your supply runs out.

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: Methylphenidate-SR tablets have a duration of action of approximately 8 hours. Therefore, Methylphenidate HCl-SR tablets may be used in place of Methylphenidate HCl tablets when the 8- hour dosage of Methylphenidate-SR corresponds to the titrated 8-hour dosage of Methylphenidate. Methylphenidate-SR tablets must be swallowed whole and never crushed or chewed.

Children (6 years and over)

Methylphenidate 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: Methylphenidate-SR tablets have a duration of action of approximately 8 hours. Therefore, Methylphenidate HCl-SR tablets may be used in place of Methylphenidate tablets when the 8- hour dosage of Methylphenidate-SR corresponds to the titrated 8-hour dosage of Methylphenidate. Methylphenidate-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.

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

Tablets:

Ritalin: available in 10 mg and 20 mg.

Both strengths contain lactose. Alcohol-free, bisulfite-free, gluten-free, parabens-free, sodium-free and tartrazine-free. Bottles of 100 and 500.

Ritalin SR: Each white, round, coated extended-release tablet, contains: Methylphenidate HCl 20 mg. Also contains lactose. Alcohol-free, bisulfite-free, gluten-free, parabens-free, sodium-free and tartrazine-free free. Bottles of 100.

The information in this monograph is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects. This information is generalized and is not intended as specific medical advice. If you have questions about the medicines you are taking or would like more information, check with your doctor, pharmacist, or nurse.