METHYLIN- methylphenidate hydrochloride_tablet, chewable

Methylphenidate hydrochloride is a central nervous system (CNS) stimulant. The mode of therapeutic action in ADHD and narcolepsy is not known. Methylphenidate is a racemic mixture comprised of the d- l-threo d-threo l-threo Cardiac Electrophysiology A formal QT study has not been conducted in subjects taking Methylin. The effect of dexmethylphenidate, the pharmacologically active d-enantiomer of Methylin, on the QT interval was evaluated in a double-blind, placebo- and open-label active (moxifloxacin)-controlled study following single doses of 40 mg dexmethylphenidate hydrochloride extended-release capsule in 75 healthy volunteers. Electrocardiograms were collected up to 12 hours postdose. Frederica’s method for heart rate correction was employed to derive the corrected QT interval (QTcF). The maximum mean prolongation of QTcF intervals was less than 5 ms, and the upper limit of the 90% confidence interval was below 10 ms for all time-matched comparisons versus placebo. This was below the threshold of clinical concern and there was no evident exposure response relationship. Absorption Following oral administration of Methylin Chewable Tablets, peak plasma methylphenidate concentrations are achieved at about 1 to 2 hours. The mean C max No clinically significant difference in methlyphenidate pharmacokinetics was observed between Methylin Chewable Tablets and immediate-release methylphenidate hydrochloride tablet. Effect of Food 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 Distribution Plasma protein binding is 10% to 33%. The volume of distribution was 2. 11 L/kg for d-methylphenidate and 1. 91 L/kg for l-methylphenidate. Elimination The mean terminal half-life (t ½ Metabolism In humans, methylphenidate is metabolized primarily via deesterification to Excretion 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 (t ½ Specific Populations Male and Female Patients, Racial Groups, and Age The effect of gender, race, and age on the pharmacokinetics of methylphenidate after Methylin administration have not been studied. Patients with Renal Impairment 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. Patients with Hepatic Impairment There is no experience with the use of Methylin Chewable Tablets in patients with hepatic insufficiency.

Methylin Chewable Tablets is indicated for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older Narcolepsy Methylin Chewable Tablets are a central nervous system (CNS) stimulant indicated for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years of age and older ( 1 Narcolepsy ( 1.

Pediatric Patients 6 Years and Older: Start with 5 mg twice daily (before breakfast and lunch); titrate the dose in weekly increments of 5 mg to 10 mg. Daily dosages above 60 mg are not recommended. 2 Adults: Administer in divided doses 2 or 3 times daily, preferably 30 to 45 minutes before meals. Maximum recommended daily dosage is 60 mg. 2 Administer with at least 8 ounces (a full glass) of water or other fluid. 2 Prior to treating patients with Methylin Chewable Tablets, assess: for the presence of cardiac disease (i. , perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) [see Warnings and Precautions ( 5. 2 the family history and clinically evaluate patients for motor or verbal tics or Tourette’s syndrome before initiating Methylin Chewable Tablets [see Warnings and Precautions ( 5. 10 Pediatric Patients 6 years and Older The recommended starting dosage is 5 mg orally twice daily before breakfast and lunch (preferably 30 to 45 minutes before meals). Increase the dosage gradually, in increments of 5 mg to 10 mg weekly. Daily dosage above 60 mg is not recommended. Adults Administer orally in divided doses 2 or 3 times daily, preferably 30 to 45 minutes before meals. The maximum recommended dosage is 60 mg daily. The average dosage is 20 to 30 mg daily. For adult patients who are unable to sleep if medication is taken late in the day, administer the last dose before 6 p. Administer Methylin Chewable Tablets with at least 8 ounces (a full glass) of water or other fluid. Do not swallow whole. Taking this product without enough liquid may cause choking [see Warnings and Precautions ( 5. 11 If paradoxical aggravation of symptoms or other adverse reactions occur, reduce dosage, or, if necessary, discontinue Methylin Chewable Tablets. If improvement is not observed after appropriate dosage adjustment over a one-month period, discontinue Methylin Chewable Tablets.

The following are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Boxed Warning, Warnings and Precautions ( 5. 3 Known hypersensitivity to methylphenidate or other ingredients of Methylin [see Contraindications ( 4 Hypertensive crisis when used concomitantly with monoamine oxidase inhibitors [see Contraindications ( 4 7 Risks to Patients with Serious Cardiac Disease [see Warnings and Precautions ( 5. 2 Increased Blood Pressure and Heart Rate [see Warnings and Precautions ( 5. 3 Psychiatric Adverse Reactions [see Warnings and Precautions ( 5. 4 Priapism [see Warnings and Precautions ( 5. 5 Peripheral Vasculopathy, including Raynaud’s Phenomenon [see Warnings and Precautions ( 5. 6 Long-Term Suppression of Growth in Pediatric Patients [see Warnings and Precautions ( 5. 7 Acute Angle Closure Glaucoma [see Warnings and Precautions ( 5. 8 Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions ( 5. 9 Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions ( 5. 10 Risk of Choking [see Warnings and Precautions ( 5. 11 Risks in Patients with Phenylketonuria [see Warnings and Precautions ( 5. 12 The following adverse reactions associated with the use of methylphenidate containing products were identified in other clinical studies, postmarketing reports, or literature. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Infections and infestations: Blood and the lymphatic system disorders: Immune system disorders: Metabolism and nutrition disorders: Psychiatric disorders: Nervous system disorders: Eye disorders: Cardiac disorders: Respiratory, thoracic and mediastinal disorders: Gastrointestinal disorders: General disorders: Hepatobiliary disorders: Skin and subcutaneous tissue disorders: Musculoskeletal and connective tissue disorders: Renal and urinary disorders: Reproductive system and breast disorders: Urogenital disorders: Vascular disorders: Investigations: Common adverse reactions: tachycardia, palpitations, headache, insomnia, anxiety, hyperhidrosis, weight loss, decreased appetite, dry mouth, nausea, and abdominal pain. ( 6 To report SUSPECTED ADVERSE REACTIONS, contact Mallinckrodt at 1-800-778-7898 or FDA at 1-800-FDA-1088 or www. gov/medwatch.

Methylin Chewable Tablets is contraindicated in patients: with a known hypersensitivity to methylphenidate or other components of Methylin Chewable Tablets. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with methylphenidate [see Adverse Reactions ( 6 receiving concomitant treatment with monoamine oxidase inhibitors (MAOIs), and also within 14 days following discontinuation of treatment with a MAOI, because of the risk of hypertensive crisis [see Drug Interactions ( 7. 1 Known hypersensitivity to methylphenidate or other components of Methylin ( 4 Concurrent treatment with a monoamine oxidase inhibitor (MAOI), or use of an MAOI within the preceding 14 days ( 4.

Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ADHD medications, including Methylin, during pregnancy. Healthcare providers are encouraged to advise patients to register by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visiting online at www. womensmentalhealth. org/research/pregnancyregistry/adhd-medications/. Risk Summary Published studies and postmarketing reports on methylphenidate use during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. There may be risks to the fetus associated with the use of CNS stimulants use during pregnancy (see Clinical Considerations) No effects on morphological development were observed in embryo-fetal development studies with oral administration of methylphenidate to pregnant rats and rabbits during organogenesis at doses up to 12 and 19 times, respectively, the maximum recommended human dose (MRHD) of 60 mg/day given to adults on a mg/m 2 (see Data) The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions CNS stimulants, such as Methylin, can cause vasoconstriction and thereby decrease placental perfusion. No fetal and/or neonatal adverse reactions have been reported with the use of therapeutic doses of methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers. Data Animal Data In embryo-fetal development studies conducted in rats and rabbits, methylphenidate was administered orally at doses of up to 75 and 200 mg/kg/day, respectively, during the period of organogenesis. Malformations (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 65 times the MRHD of 60 mg/day given to adults on a mg/m 2 2 2 2 2 2 Risk Summary Limited published literature, based on milk sampling from seven mothers reports that methylphenidate is present in human milk, which resulted in infant doses of 0. 7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1. There are no reports of adverse effects on the breastfed infant and no effects on milk production. Long-term neurodevelopmental effects on infants from stimulant exposure are unknown. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Methylin and any potential adverse effects on the breastfed infant from Methylin or from the underlying maternal condition. Clinical Considerations Monitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain. The safety and effectiveness of Methylin for the treatment of ADHD have been established in pediatric patients six years of age and older. The safety and effectiveness of Methylin in pediatric patients under six years of age have not been established. The long-term efficacy of methylphenidate in pediatric patients has not been established. Long-Term Suppression of Growth Growth should be monitored during treatment with stimulants, including Methylin. Pediatric patients who are not growing or gaining weight as expected may need to have their treatment interrupted [see Warnings and Precautions ( 5. 1 Juvenile Animal Toxicity Data In a study conducted in young rats, methylphenidate was administered orally at doses of up to 100 mg/kg/day for 9 weeks, starting early in the postnatal period (postnatal Day 7) and continuing through sexual maturity (postnatal Week 10). When these animals were tested as adults (postnatal Weeks 13 to 14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day (approximately 4 times the MRHD of 60 mg/day given to children on a mg/m 2 2 2 Methylin has not been studied in the geriatric population. Methylin has not been studied in patients with renal impairment.

Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed. 1 Table 1 presents clinically important drug interactions with Methylin. Table 1: Drugs Having Clinically Important Interactions with Methylin Monoamine Oxidase Inhibitors (MAOI) Clinical Impact: Concomitant use of MAOIs and CNS stimulants, including Methylin, can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure [see Contraindications ( 4 Intervention: Concomitant use of Methylin with monoamine oxidase inhibitors (MAOIs) or within 14 days after discontinuing MAOI treatment is contraindicated. Antihypertensive Drugs Clinical Impact: Methylin may decrease the effectiveness of drugs used to treat hypertension [see Warnings and Precautions ( 5. 3 Intervention: Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed. Halogenated Anesthetics Clinical Impact: Concomitant use of halogenated anesthetics and Methylin may increase the risk of sudden blood pressure and heart rate increase during surgery. Intervention: Avoid use of Methylin in patients being treated with anesthetics on the day of surgery. Risperidone Clinical Impact: Combined use of methylphenidate with risperidone when there is a change, whether an increase or decrease, in dosage of either or both medications, may increase the risk of extrapyramidal symptoms (EPS). Intervention: Monitor for signs of EPS.

OVERDOSAGE
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.
NONCLINICAL TOXICOLOGY
Carcinogenesis 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 5 times the maximum recommended human dose (MRDH) given to adults on a mg/m 2 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 7 times the MRHD (adults) on a mg/m 2 In a 24-week carcinogenicity study in the transgenic mouse strain p53+/-, which is sensitive to genotoxic carcinogens, there was no evidence of carcinogenicity. Male and female mice were fed diets containing the same concentration of methylphenidate as in the lifetime carcinogenicity study; the high-dose groups were exposed to 60 to 74 mg/kg/day of methylphenidate. Mutagenesis Methylphenidate was not mutagenic in the in vitro in vitro in vitro in vitro in vivo Im pairment of Fertility No human data on the effect of methylphenidate on fertility are available. Methylphenidate did not impair fertility in male or female mice that were fed diets containing the drug in an 18-week continuous breeding study. The study was conducted at doses up to 160 mg/kg/day, approximately 13 times the maximum recommended human dose of 60 mg/day given to adults on a mg/m 2
MEDICATION GUIDE
MEDICATION GUIDE METHYLIN registered (METH il in) (methylphenidate hydrochloride), CII What is the most important information I should know about Methylin Chewable Tablets? Methylin Chewable Tablets may cause serious side effects, including: Abuse, misuse, and addiction. Your healthcare provider should check you or your child’s risk for abuse, misuse, and addiction before starting treatment with Methylin Chewable Tablets and will monitor you or your child during treatment. Methylin Chewable Tablets may lead to physical dependence after prolonged use, even if taken as directed by your healthcare provider. Do not give Methylin Chewable Tablets to anyone else. See “What is Methylin Chewable Tablets?” Keep Methylin Chewable Tablets in a safe place and properly dispose of any unused medicine. See “How should I store Methylin Chewable Tablets?” Tell your healthcare provider if you or your child have ever abused or been dependent on alcohol, prescription medicines, or street drugs. Risks for people with serious heart disease. Your healthcare provider should check you or your child carefully for heart problems before starting and during treatment with Methylin Chewable Tablets. Tell your healthcare provider if you or your child have any heart problems, heart disease, or heart defects. Call your healthcare provider right away or go to the nearest hospital emergency room right away if you or your child have any signs of heart problems, such as chest pain, shortness of breath, or fainting during treatment with Methylin Chewable Tablets. Increased blood pressure and heart rate. Your healthcare provider should check you or your child’s blood pressure and heart rate regularly during treatment with Methylin Chewable Tablets. Mental (psychiatric) problems, including: new or worse behavior or thought problems new or worse bipolar illness new psychotic symptoms (such as hearing voices, or seeing or believing things that are not real) or new manic symptoms Tell your healthcare provider about any mental problems you or your child have, or about a family history of suicide, bipolar illness, or depression. Call your healthcare provider right away if you or your child have any new or worsening mental symptoms or problems during treatment with Methylin Chewable Tablets, especially hearing voices, seeing or believing things that are not real, or new manic symptoms. What is Methylin Chewable Tablets? Methylin Chewable Tablets is a central nervous system (CNS) stimulant prescription medicine used for the treatment of: Attention Deficit Hyperactivity Disorder (ADHD) in people 6 years of age and older. Methylin Chewable Tablets may help increase attention and decrease impulsiveness and hyperactivity in people with ADHD. a sleep disorder called narcolepsy. It is not known if Methylin Chewable Tablets is safe and effective in children under 6 years of age. Methylin Chewable Tablets is a federally controlled substance (CII) because it contains methylphenidate that can be a target for people who abuse prescription medicines or street drugs. Do not take Methylin Chewable Tablets if you or your child: are taking or have stopped taking within the past 14 days, a medicine called a monoamine oxidase inhibitor (MAOI). Before taking Methylin Chewable Tablets tell your healthcare provider about all of your or your child’s medical conditions, including if you or your child: have heart problems, heart disease, heart defects, or high blood pressure have mental problems including psychosis, mania, bipolar illness, or depression, or have a family history of suicide, bipolar illness, or depression have circulation problems in fingers or toes have eye problems, including increased pressure in your eye, glaucoma, or problems with your close-up vision (farsightedness) have or had repeated movements or sounds (tics) or Tourette’s syndrome, or have a family history of tics or Tourette’s syndrome have trouble swallowing have phenylketonuria (PKU). The artificial sweetener aspartame in Methylin Chewable Tablets contains phenylalanine, which can be harmful to people with PKU. are pregnant or plan to become pregnant. It is not known if Methylin Chewable Tablets will harm your unborn baby. There is a pregnancy registry for women who are exposed to Methylin Chewable Tablets during pregnancy. The purpose of the registry is to collect information about the health of women exposed to Methylin Chewable Tablets and their baby. If you or your child becomes pregnant during treatment with Methylin Chewable Tablets, talk to your healthcare provider about registering with the National Pregnancy Registry for ADHD Medications at 1-866-961-2388 or visit online at www.womensmentalhealth.org/research/pregnancyregistry/adhd-medications/. are breastfeeding or plan to breastfeed. Methylin passes into breast milk. Talk to your healthcare provider about the best way to feed the baby during treatment with Methylin Chewable Tablets. Tell your healthcare provider about all of the medicines that you or your child take, Methylin Chewable Tablets and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be during treatment with Methylin Chewable Tablets. Your healthcare provider will decide whether Methylin Chewable Tablets can be taken with other medicines. Especially tell your healthcare provider if you or your child take an monoamine oxidase inhibitor (MAOI). Know the medicines that you or your child take. Keep a list of your or your child’s medicines with you to show your or your child’s healthcare provider and pharmacist when you or your child get a new medicine. Do not start any new medicine during treatment with Methylin Chewable Tablets without talking to your or your child’s healthcare provider first. How should I take Methylin Chewable Tablets? Take Methylin Chewable Tablets exactly as prescribed by your healthcare provider. For children 6 years of age and older: Take Methylin Chewable Tablets 2 times a day, 30 to 45 minutes before breakfast and lunch. For adults: Take Methylin Chewable tablets 2 or 3 times a day, 30 to 45 minutes before a meal. If you have trouble sleeping when Methylin Chewable Tablets is taken late in the day, take your last dose before 6 p.m. Chew Methylin Chewable Tablets well and swallow with at least 8 ounces (a full glass) of water or other liquid. Do not swallow Methylin Chewable Tablets whole. If you do not take enough liquid with Methylin Chewable Tablets, this can cause you to choke. Stop taking Methylin Chewable Tablets and get medical help right away if you or your child have chest pain, vomiting, trouble swallowing, or trouble breathing after taking Methylin Chewable Tablets. If you or your child takes too much Methylin Chewable Tablets, call your healthcare provider or Poison Help line at 1-800-222-1222 or go to the nearest hospital emergency room right away. What are the possible side effects of Methylin Chewable Tablets? Methylin Chewable Tablets may cause serious side effects, including: See “What is the most important information I should know about Methylin Chewable Tablets?” Painful and prolonged erections (priapism). If you or your child develops priapism, get medical help right away. Circulation problems in fingers and toes (peripheral vasculopathy, including Raynaud’s phenomenon). Signs and symptoms may include: fingers or toes may feel numb, cool, or painful fingers or toes may change color from pale, to blue, to red Tell your healthcare provider if you or your child have numbness, pain, skin color change, or sensitivity to temperature in the fingers or toes or if you or your child have any signs of unexplained wounds appearing on fingers or toes during treatment with Methylin Chewable Tablets. Slowing of growth (height and weight) in children. Eye problems (increased pressure in the eye and glaucoma). New or worsening tics or worsening Tourette’s syndrome. The most common side effects of Methylin Chewable Tablets include: increased heart rate irregular heartbeat (palpitations) headache trouble sleeping anxiety sweating weight loss decreased appetite dry mouth nausea stomach (abdominal) pain These are not all possible side effects of Methylin Chewable Tablets. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store Methylin Chewable Tablets? Store Methylin Chewable Tablets at room temperature between 68° to 77°F (20° to 25°C). Store Methylin Chewable Tablets in a safe place, like a locked cabinet. Protect Methylin Chewable Tablets from moisture. Dispose of remaining, unused, or expired Methylin Chewable Tablets by a medicine take-back program at a U.S. Drug Enforcement Administration (DEA) authorized collection site. If no take-back program or DEA authorized collector is available, mix Methylin Chewable Tablets with an undesirable, nontoxic substance such as dirt, cat litter, or used coffee grounds to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and throw away Methylin Chewable Tablets in the household trash. Visit ww.fda.gov/drugdisposal for additional information on disposal of unused medicines. Keep Methylin Chewable Tablets and all medicines out of the reach of children. General information about the safe and effective use of Methylin Chewable Tablets. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Methylin Chewable Tablets for a condition for which it was not prescribed. Do not give Methylin Chewable Tablets to other people, even if they have the same symptoms. It may harm them, and it is against the law. You can ask your pharmacist or healthcare provider for information about Methylin Chewable Tablets that is written for health professionals. What are the ingredients in Methylin Chewable Tablets? Active Ingredient: Inactive Ingredients: Distributed by: Shionogi Inc., Florham Park, NJ 07932 Manufactured by: SpecGx LLC, Webster Groves, MO 63119 USA For more information, you may also contact Shionogi Inc. at 1-800-849-9707 or visit the website at www.methylinrx.com. This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised 01/2025

SHIONOGI INC.

METHYLIN- methylphenidate hydrochloride_tablet, chewable Product manual source documgent