Methylin Chewable Tablets

Name: Methylin Chewable Tablets

Side effects

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; libido changes; and rhabdomyolysis. 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 abdominal 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.

What is methylphenidate (concerta, metadate cd, metadate er, methylin, methylin er, ritalin, ritalin la, ritalin-sr)?

Methylphenidate is a central nervous system stimulant. It affects chemicals in the brain and nerves that contribute to hyperactivity and impulse control.

Methylphenidate is used to treat attention deficit disorder (ADD), attention deficit hyperactivity disorder (ADHD), and narcolepsy.

Methylphenidate may also be used for purposes not listed in this medication guide.

What is the most important information i should know about methylphenidate?

Do not use methylphenidate if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you use methylphenidate before the MAO inhibitor has cleared from your body.

Do not use this medication if you are allergic to methylphenidate or if you have glaucoma, overactive thyroid, severe high blood pressure, tics or Tourette's syndrome, angina, heart failure, heart rhythm disorder, recent heart attack, a hereditary condition such as fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency, or severe anxiety, tension, or agitation.

Methylphenidate may be habit-forming and should be used only by the person it was prescribed for. Never share methylphenidate with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

Clinical pharmacology

Methylphenidate is a racemic mixture comprised of the d- and l-threo enantiomers. The d-threo enantiomer is more pharmacologically active than the l-threo enantiomer.

Methylphenidate HCl is a central nervous system (CNS) stimulant.

The mode of therapeutic action in humans is not completely understood, but methylphenidate presumably activates the brain stem arousal system and cortex to produce its stimulant effect. Methylphenidate is thought to block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

There is neither specific evidence which clearly establishes the mechanism whereby Methylin produces its mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.

Pharmacokinetics

Absorption

Methylin Chewable Tablets are readily absorbed. Following oral administration of Methylin Chewable Tablets, peak plasma methylphenidate concentrations are achieved at about 1 to 2 hours. Methylin Chewable Tablets have been shown to be bioequivalent to Ritalin® tablet. The mean Cmax following a 20 mg dose is approximately 10 ng/mL.

Food Effect

In a study in adult volunteers investigating the effects of a high-fat meal on the bioavailability of Methylin Chewable Tablets at a dose of 20 mg, the presence of food delayed the peak concentrations by approximately 1 hour (1.5 hours, fasted and 2.4 hours, fed). Overall, a high-fat meal increased the AUC of Methylin Chewable Tablets by about 20%, on average. Through a cross-study comparison, the magnitude of food effect is found to be comparable between the Methylin Chewable Tablets and Ritalin, the immediate release tablet.

Metabolism and Excretion

In humans, methylphenidate is metabolized primarily via deesterification to alpha-phenylpiperidine acetic acid (PPA, ritalinic acid). The metabolite has little or no pharmacologic activity.

After oral dosing of radiolabeled methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main urinary metabolite was PPA, accounting for approximately 80% of the dose.

The pharmacokinetics of the Methylin Chewable Tablets have been studied in healthy adult volunteers. The mean terminal half-life (t½) of methylphenidate following administration of 20 mg Methylin Chewable Tablets (t½ = 3 hours) is comparable to the mean terminal t½ following administration of Ritalin (methylphenidate hydrochloride immediate-release tablets) (t½ = 2.8 hours) in healthy adult volunteers.

Special Populations

Gender – The effect of gender on the pharmacokinetics of methylphenidate after Methylin Chewable Tablets administration has not been studied.

Race – The influence of race on the pharmacokinetics of methylphenidate after Methylin Chewable Tablets administration has not been studied.

Age – The pharmacokinetics of methylphenidate after Methylin Chewable Tablets administration have not been studied in pediatrics.

Renal Insufficiency

There is no experience with the use of Methylin Chewable Tablets in patients with renal insufficiency. After oral administration of radiolabeled methylphenidate in humans, methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of ritalinic acid. Since renal clearance is not an important route of methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of Methylin Chewable Tablets.

Hepatic Insufficiency

There is no experience with the use of Methylin Chewable Tablets in patients with hepatic insufficiency.

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 Methylin 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 Methylin is usually not indicated.

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

Information for Patients

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with methylphenidate and should counsel them in its appropriate use. A patient Medication Guide is available for Methylin Chewable Tablets. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Physicians are advised to discuss the following issues with patients for whom they prescribe Methylin:

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.

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.

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

  • Instruct patients beginning treatment with Methylin 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 Methylin.
  • Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Phenylketonurics – Phenylalanine is a component of aspartame. Each 2.5 mg Methylin Chewable Tablet contains 0.42 mg of phenylalanine; each 5.0 mg Methylin Chewable Tablet contains 0.84 mg of phenylalanine and each 10.0 mg Methylin Chewable Tablet contains 1.68 mg of phenylalanine.

Drug Interactions

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

Human pharmacologic studies have shown that Methylin 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 Methylin.

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 Methylin 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.

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; and libido changes. 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 abdominal 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.

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.

Adults

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.

Children (6 years and over)

Methylin 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.

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

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

Methylin 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.

PRINCIPAL DISPLAY PANEL - 2.5 mg

NDC 59630-760-10

100 TABLETS

Methylin®
Chewable Tablets
methylphenidate HCl chewable tablets

CII

2.5 mg Rx only

Each tablet contains: Methylphenidate Hydrochloride USP. . . . . . . 2.5 mg

PHARMACIST: PLEASE DISPENSE WITH
MEDICATION GUIDE PROVIDED WITH PRODUCT

SHIONOGI INC.

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