FDA

Methylin

Approved 19 Dec 2002OralSolution

The FDA lists this product in 5 strengths and forms.

Indications

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

Contraindications

Methylin is contraindicated in patients: with known hypersensitivity to methylphenidate or other components of Methylin. 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), or within 14 days following discontinuation of treatment with an MAOI, because of the risk of hypertensive crises [see Drug Interactions ( 7 )] .

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)

Warnings and precautions

Risks to Patients with Serious Cardiac Disease : Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease. ( 5.2 ) Increased Blood Pressure and Heart Rate : Monitor blood pressure and pulse. ( 5.3 ) Psychiatric Adverse Reactions : Prior to initiating Methylin, screen patients for risk factors for developing a manic episode.

If new psychotic or manic symptoms occur, consider discontinuing Methylin. ( 5.4 ) Priapism : If abnormally sustained or frequent and painful erections occur, patients should seek immediate medical attention. ( 5.5 ) Peripheral Vasculopathy, Including Raynaud’s Phenomenon : Careful observation for digital changes is necessary during Methylin treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for patients who develop signs or symptoms of peripheral vasculopathy.

( 5.6 ) Long-Term Suppression of Growth in Pediatric Patients : Closely monitor (height and weight) in pediatric patients. Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted. ( 5.7 ) Acute Angle Closure Glaucoma : Methylin-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.

At a glance

Brand name: Methylin
Active substance: methylphenidate hydrochloride
Route: Oral
Dosage form: Solution
Applicant: Specgx LLC
Status: Prescription
FDA approval: 19 Dec 2002
Application: NDA021419-001

Indications

Contraindications

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)

Warnings and precautions

Pregnancy and breastfeeding

8.1Pregnancy 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 register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388. 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 basis.

However, spina bifida was observed in rabbits at a dose 65 times the MRHD given to adults. A decrease in pup body weight was observed in a pre- and post-natal development study with oral administration of methylphenidate to rats throughout pregnancy and lactation at doses 7 times the MRHD given to adults (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. In the U.S. 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 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (19 times the MRHD given to adults on a mg/m 2 basis). There was no evidence of morphological development effects in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (12 times the MRHD of 60 mg/day given to adults on a mg/m 2 basis), which was also maternally toxic.

The no effect level for embryo-fetal development in rats was 25 mg/kg/day (4 times the MRHD on a mg/m 2 basis). When methylphenidate was administered to rats throughout pregnancy and lactation at doses of up to 45 mg/kg/day, offspring body weight gain was decreased at the highest dose (7 times the MRHD of 60 mg/day given to adults on a mg/m 2 basis), but no other effects on postnatal development were observed. The no effect level for pre- and postnatal development in rats was 15 mg/kg/day (~2 times the MRHD given to adults on a mg/m 2 basis).

Adverse reactions

The following adverse reactions are discussed in more detail in other sections of the labeling: Abuse, misuse, and addiction [see Warnings and Precautions ( 5.1 ), Drug Abuse and Dependence ( 9.2 , 9.3 )] Known hypersensitivity to methylphenidate or other components of Methylin [see Contraindications ( 4 )] Hypertensive crisis when used concomitantly with monoamine oxidase inhibitors [see Contraindications ( 4 ), Drug Interactions ( 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 )] The following adverse reactions associated with the use of methylphenidate containing products were identified in 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: nasopharyngitis Blood and the lymphatic system disorders: leukopenia, thrombocytopenia, anemia, pancytopenia Immune system disorders: hypersensitivity reactions, including angioedema and anaphylaxis, auricular swelling, bullous conditions, eruptions, exanthemas Metabolism and nutrition disorders: decreased appetite, reduced weight gain and suppression of growth during prolonged use in pediatric patients Psychiatric disorders: insomnia, anxiety, restlessness, agitation, psychosis (sometimes with visual and tactile hallucinations), depressed mood, affect lability, mania, disorientation, libido changes Nervous system disorders: headache, dizziness, tremor, dyskinesia including choreoatheetoid movements, drowsiness, convulsions, cerebral arteritis and/or occlusion, serotonin syndrome in combination with serotonergic drugs, migraine, motor and verbal tics Eye disorders: blurred vision, difficulties in visual accommodation, diplopia, mydriasis, increased intraocular pressure Cardiac disorders: tachycardia, palpitations, increased blood pressure, arrhythmias, angina pectoris, sudden cardiac death, myocardial infarction, bradycardia, extrasystole Respiratory, thoracic and mediastinal disorders: cough, pharyngolaryngeal pain, dyspnea Gastrointestinal disorders: dry mouth, nausea, vomiting, abdominal pain, dyspepsia, diarrhea General disorders: fatigue, hyperpyrexia Hepatobiliary disorders: abnormal liver function, ranging from transaminase elevation to severe hepatic injury Skin and subcutaneous tissue disorders: hyperhidrosis, pruritus, urticaria, exfoliative dermatitis, scalp hair loss, erythema multiforme rash, thrombocytopenic purpura angioneurotic edema, erythema, fixed drug eruption Musculoskeletal and connective tissue disorders: arthralgia, muscle cramps, rhabdomyolysis, myalgia, muscle twitching Renal and urinary disorders: hematuria Reproductive system and breast disorders: gynecomastia Urogenital disorders: priapism Vascular disorders: peripheral coldness, Raynaud’s phenomenon Investigations: weight loss 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 Shionogi Inc. at 1-800-849-9707 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Methylin

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Methylin

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Abuse, Misuse, and Addiction

5.2Risks to Patients with Serious Cardiac Disease

5.3Increased Blood Pressure and Heart Rate

5.4Psychiatric Adverse Reactions Exacerbation of Pre-Existing Psychosis

5.5Priapism Prolonged

5.6Peripheral Vasculopathy, Including Raynaud’s Phenomenon

5.7Long-Term Suppression of Growth in Pediatric Patients

5.8Acute Angle Closure Glaucoma

5.9Increased Intraocular Pressure and Glaucoma

Interactions

7.1Clinically Important Drug Interactions with Methylin Table

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

Adverse reactions

Composition

Strengths and forms

Official product information