Methylphenidate hydrochloride is a mild central nervous system (CNS) stimulant, available as 2.5 mg, 5 mg and 10 mg chewable tablets for oral administration. Methylphenidate hydrochloride is methyl α-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.
Each Methylphenidate Hydrochloride Chewable Tablet, for oral administration, contains 2.5 mg, 5 mg or 10 mg of methylphenidate hydrochloride USP. In addition, Methylphenidate Hydrochloride Chewable Tablets also contain the following inactive ingredients: microcrystalline cellulose, grape flavor, guar gum, maltose, stearic acid, and sucralose.

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 methylphenidate hydrochloride 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
Methylphenidate Hydrochloride Chewable Tablets are readily absorbed. Following oral administration of Methylphenidate Hydrochloride Chewable Tablets, peak plasma methylphenidate concentrations are achieved at about 1 to 2 hours. Methylphenidate Hydrochloride 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 Methylphenidate Hydrochloride 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 Methylphenidate Hydrochloride Chewable Tablets by about 20%, on average. Through a cross-study comparison, the magnitude of food effect is found to be comparable between the Methylphenidate Hydrochloride 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 Methylphenidate Hydrochloride Chewable Tablets have been studied in healthy adult volunteers. The mean terminal half-life (t½) of methylphenidate following administration of 20 mg Methylphenidate Hydrochloride 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 Methylphenidate Hydrochloride Chewable Tablets administration has not been studied.

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

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

Renal Insufficiency
There is no experience with the use of Methylphenidate Hydrochloride 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 Methylphenidate Hydrochloride Chewable Tablets.

Hepatic Insufficiency
There is no experience with the use of Methylphenidate Hydrochloride Chewable Tablets in patients with hepatic insufficiency.

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 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.

Methylphenidate Hydrochloride Chewable Tablets are contraindicated in patients known to be hypersensitive to methylphenidate or other components of the drug.

Methylphenidate hydrochloride 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).

Abuse, Misuse, and Addiction
Methylphenidate Hydrochloride Chewable Tablets have a high potential for abuse and misuse. The use of Methylphenidate Hydrochloride Chewable Tablets exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Methylphenidate Hydrochloride Chewable Tablets can be diverted for non-medical use into illicit channels or distribution (see DRUG ABUSE and DEPENDENCE). Misuse and abuse of CNS stimulants, including Methylphenidate Hydrochloride Chewable Tablets can result in overdose and death (see OVERDOSAGE), and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.

Before prescribing Methylphenidate Hydrochloride Chewable Tablets, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their families about these risks and proper disposal of any unused drug. Advise patients to store methylphenidate in a safe place, preferably locked, and instruct patients to not give Methylphenidate Hydrochloride Chewable Tablets to anyone else. Throughout Methylphenidate Hydrochloride Chewable Tablets treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.

Risks to Patients with Serious Cardiac Disease
Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who are treated with CNS stimulants at the recommended ADHD dosages.


Avoid Methylphenidate Hydrochloride Chewable Tablets use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
Increased Blood Pressure and Heart Rate
CNS stimulants cause an increase in blood pressure (mean increase about 2 to 4 mm Hg) and heart rate (mean increase about 3 to 6 bpm). Monitor all patients for potential tachycardia and hypertension.

Psychiatric Adverse Reactions
Exacerbations of Pre-Existing Psychosis – CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.
Induction of a Manic Episode in Patients with Bipolar Disease – CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).

New Psychotic or Manic Symptoms – CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in approximately 0.1% of CNS stimulant-treated patients, compared with 0% of placebo-treated patients. If such symptoms occur, consideration discontinuing Methylphenidate Hydrochloride Chewable Tablets.

Seizures
There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Priapism
Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate products in both pediatric and adult patients.  Priapism was not reported with drug initiation but developed after some time on the drug, often subsequent to an increase in dose.  Priapism has also appeared during a period of drug withdrawal (drug holidays or discontinuation). Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.

Peripheral Vasculopathy, Including Raynaud’s Phenomenon
Stimulants, including methylphenidate hydrochloride, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon.  Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown.  Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment.  Signs and symptoms generally improve after reduction in dose or discontinuation of drug.  Careful observation for digital changes is necessary during treatment with ADHD stimulants.  Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Long-Term Suppression of Growth in Pediatric Patients
CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients.

Careful follow-up of weight and height in pediatric patients ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated pediatric patients over 36 months (to the ages of 10 to 13 years), suggests that pediatric patients who received methylphenidate for 7 days per week throughout the year had a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this development period.

Closely monitor growth (weight and height) in Methylphenidate Hydrochloride Chewable Tablets-treated pediatric patients. Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted (see PRECAUTIONS, PEDIATRIC USE).

Acute Angle Closure Glaucoma
There have been reports of angle closure glaucoma associated with methylphenidate treatment.

Although the mechanism is not clear, Methylphenidate Hydrochloride Chewable Tablets-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.

Increased Intraocular Pressure and Glaucoma
There have been reports of an elevation of intraocular pressure (IOP) associated with methylphenidate treatment (see Adverse Reactions).

Prescribe Methylphenidate Hydrochloride Chewable Tablets to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor Methylphenidate Hydrochloride Chewable Tablets-treated patients with a history of abnormally increased IOP or open angle glaucoma.

Motor and Verbal Tics, and Worsening of Tourette’s Syndrome
CNS stimulants, including methylphenidate, have been associated with the onset or exacerbation of motor and verbal tics. Worsening of Tourette’s syndrome has also been reported. Assess the family history and clinically evaluate patients for tics or Tourette’s syndrome before initiating Methylphenidate Hydrochloride Chewable Tablets. Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome with Methylphenidate Hydrochloride Chewable Tablets, and discontinue treatment if clinically appropriate.

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

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 increased intraocular pressure and glaucoma, motor and verbal tics. 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 severe hepatic injury; isolated cases of cerebral arteritis and/or occlusion; leukopenia and/or anemia; transient depressed mood; a few instances of scalp hair loss; serotonin syndrome in combination with serotonergic drugs. 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.

To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Clinical Effects of Overdose
Overdose of CNS stimulants is characterized by the following sympathomimetic effects:

• Cardiovascular effects including tachyarrhythmias, and hypertension or hypotension. Vasospasm, myocardial infarction, or aortic dissection may precipitate sudden cardiac death. Takotsubo cardiomyopathy may develop.
• CNS effects including psychomotor agitation, confusion, and hallucinations. Serotonin syndrome, seizures, cerebral vascular accidents, and coma may occur.
• Life-threatening hyperthermia (temperatures greater than 104°F) and rhabdomyolysis may develop.

Overdose Management
Consider the possibility of multiple drug ingestion. Because methylphenidate has a large volume of distribution and is rapidly metabolized, dialysis is not useful. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

Prior to treating patients with Methylphenidate Hydrochloride Chewable Tablets assess:

• for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) (see WARNINGS).
• the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome (see WARNINGS).

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)

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

If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage, or, if necessary, discontinue Methylphenidate Hydrochloride Chewable Tablets. Methylphenidate Hydrochloride Chewable Tablets should be periodically discontinued to assess the patient’s condition. If improvement is not observed after appropriate dosage adjustment over a one-month period, the drug should be discontinued.

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

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

Each Methylphenidate Hydrochloride Chewable Tablet 2.5 mg is available as a white to off-white colored, grape flavored, rounded square shaped tablet with a convex surface, debossed with "τ" above "CHEW" on one side and "2.5" on the other side.

Bottles of 100 . . . . . . . NDC 64980-221-01

Each Methylphenidate Hydrochloride Chewable Tablet 5 mg is available as a white to off-white colored, grape flavored, rounded square shaped tablet with a convex surface, debossed with "τ" above "CHEW" on one side and "5" on the other side.

Bottles of 100 . . . . . . . NDC 64980-222-01

Each Methylphenidate Hydrochloride Chewable Tablet 10 mg is available as a white to off-white colored, grape flavored, scored rounded square shaped tablet with a convex surface, debossed with "τ" bisect "CHEW" on one side and  "10" on the other side.

Bottles of 100 . . . . . . . NDC 64980-223-01

Protect from moisture. Dispense in tight container with child-resistant closure.

Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Ritalin is a registered trademark of Novartis Corporation.

Manufactured for:
Rising Pharma Holdings, Inc.
East Brunswick, NJ 08816

Rev. 02/2024
PIR22301-04

Methylphenidate Hydrochloride Chewable Tablets 2.5 mg, 5 mg, and 10 mg CII

Read the Medication Guide that comes with Methylphenidate Hydrochloride Chewable Tablets before you or your child starts taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your or your child's treatment with Methylphenidate Hydrochloride Chewable Tablets.

Methylphenidate Hydrochloride Chewable Tablets, 2.5 mg
100 count

Methylphenidate Hydrochloride Chewable Tablets, 5 mg
100 count

Methylphenidate Hydrochloride Chewable Tablets, 10 mg
100 count