RELEXXII is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults (up to the age of 65 years) and pediatric patients 6 years of age and older [ see Clinical Studies ( 14 )] . Limitations of Use The use of RELEXXII is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage [see Warnings and Precautions ( 5.7 ), Use in Specific Populations ( 8.4 )] .
RELEXXII ® is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults (up to the age of 65 years) and pediatric patients 6 years of age and older ( 1 ). Limitations of Use The use of RELEXXII is not recommended in pediatric patients younger than 6 years of age because they had higher plasma exposure and a higher incidence of adverse reactions (e.g., weight loss) than patients 6 years and older at the same dosage ( 5.7 , 8.4 ).
Contraindications
RELEXXII is contraindicated in patients: with a known hypersensitivity to methylphenidate or other components of RELEXXII. Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other methylphenidate products [see Adverse Reactions ( 6.2 )] . 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 RELEXXII ( 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 serious cardiac disease. ( 5.2 ) Increased Blood Pressure and Heart Rate: Monitor blood pressure and pulse. ( 5.3 ) Psychiatric Adverse Reactions: Prior to initiating RELEXXII, screen patients for risk factors for developing a manic episode.
Two medicines in one question?
Name two or more medicines and Osler runs an interaction check. A severe interaction is stated at the very top of the answer.
If new psychotic or manic symptoms occur, consider discontinuing RELEXXII. ( 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 RELEXXII 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 growth (height and weight) in pediatric patients. Pediatric patients not growing or gaining weight as expected may need to have their treatment interrupted. ( 5.7 ) Gastrointestinal Obstruction: Avoid use with preexisting GI narrowing. ( 5.8 ) Acute Angle Closure Glaucoma: RELEXXII-treated patients considered at risk for acute angle closure glaucoma (e.g., patients with significant hyperopia) should be evaluated by an ophthalmologist.
( 5.9 ) Increased Intraocular Pressure (IOP) and Glaucoma: Prescribe RELEXXII to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk. Closely monitor patients with a history of increased IOP or open angle glaucoma. ( 5.10 ) Motor and Verbal Tics, and Worsening of Tourette’s Syndrome: Before initiating RELEXXII, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome.
Regularly monitor patients for the emergence or worsening of tics or Tourette’s syndrome. Discontinue treatment if clinically appropriate. ( 5.11 )
5.1Abuse, Misuse, and Addiction
RELEXXII has a high potential for abuse and misuse. The use of RELEXXII exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. RELEXXII can be diverted for non-medical use into illicit channels or distribution [see Drug Abuse and Dependence ( 9.2 , 9.3 )]. Misuse and abuse of CNS stimulants, including RELEXXII, can result in overdose and death [see Overdosage ( 10 )] , and this risk is increased with higher doses or unapproved methods of administration, such as snorting or injection.
Before prescribing RELEXXII, 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 RELEXXII in a safe place, preferably locked, and instruct patients to not give RELEXXII to anyone else. Throughout RELEXXII treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction.
5.2Risks to Patients with Serious Cardiac Disease
Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were taking CNS stimulants at the recommended ADHD dosage. Avoid RELEXXII use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease.
5.3Increased Blood Pressure and Heart Rate
CNS stimulants cause an increase in blood pressure (mean increase approximately 2 to 4 mm Hg) and heart rate (mean increase approximately 3 to 6 bpm) [see Adverse Reactions ( 6.1 )]. Some patients may have larger increases. Monitor all RELEXXII-treated patients for hypertension and tachycardia.
5.4Psychiatric Adverse Reactions Exacerbation of Pre-existing Psychosis
CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a preexisting psychotic disorder. Induction of a Manic Episode in Patients with Bipolar Disorder CNS stimulants may induce a manic or mixed episode in patients. Prior to initiating RELEXXII treatment, screen patients for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms, a family history of suicide, bipolar disorder, and depression).
New Psychotic or Manic Symptoms CNS stimulants, at the recommended dosage, 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 to 0% of placebo-treated patients.
If such symptoms occur, consider discontinuing RELEXXII.
5.5Priapism Prolonged
and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate use, including another formulation of methylphenidate hydrochloride extended-release tablets, in both adult and pediatric male patients [see Adverse Reactions ( 6.2 )] . Although priapism was not reported with methylphenidate initiation, it developed after some time on methylphenidate, often subsequent to an increase in dosage.
Priapism also occurred during a methylphenidate withdrawal (drug holidays or during discontinuation). RELEXXII-treated patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.
5.6Peripheral
Vasculopathy, including Raynaud’s Phenomenon CNS stimulants, such as RELEXXII, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, sequelae have included digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports and at the therapeutic dosage in all age groups throughout the course of treatment.
Signs and symptoms generally improved after reduction or discontinuation of the CNS stimulant. Careful observation for digital changes is necessary during RELEXXII treatment. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for RELEXXII-treated patients who develop signs or symptoms of peripheral vasculopathy.
5.7Long-Term Suppression of Growth in Pediatric Patients
RELEXXII is not approved for use and is not recommended in pediatric patients below 6 years of age [see Use in Specific Populations ( 8.4 )] . 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 nonmedication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and nonmedication-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 RELEXXII-treated pediatric patients. Pediatric patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
5.8Potential for Gastrointestinal Obstruction Because the
RELEXXII tablet is nondeformable and does not appreciably change in shape in the GI tract, RELEXXII should not ordinarily be administered to patients with preexisting severe gastrointestinal narrowing (pathol
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
Antihypertensive Drugs: Monitor blood pressure. Adjust dosage of antihypertensive drug as needed ( 7.1 )
7.1Clinically Important Drug Interactions Table
6 presents clinically important drug interactions with RELEXXII. Table 6: Drugs Having Clinically Important Interactions with RELEXXII Monoamine Oxidase Inhibitors (MAOI) Clinical Impact: Concomitant use of MAOIs and CNS stimulants 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: Do not administer RELEXXII concomitantly with MAOIs or within 14 days after discontinuing MAOI treatment. Antihypertensive Drugs Clinical Impact: RELEXXII 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 RELEXXII may increase the risk of sudden blood pressure and heart rate increase during surgery.
Intervention: Avoid use of RELEXXII 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.
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 RELEXXII, during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for ADHD Medications at 1-866-961-2388. Risk Summary Published studies and post-marketing 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 are risks to the fetus associated with the use of central nervous system (CNS) stimulants during pregnancy ( see Clinical Considerations). No effects on morphological development were observed in development studies with oral administration of methylphenidate to pregnant rats at doses up to 4 times the maximum recommended human dose (MRHD) of 72 mg/day given to adults on a mg/m 2 basis. However, malformations were observed in rabbits at a dose 54 times the MRHD given to adults.
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 RELEXXII, 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 development studies conducted in rats and rabbits, methylphenidate was administered at doses up to 30 and 200 mg/kg/day, respectively. Methylphenidate has been shown to cause malformations in rabbits when given in doses of 200 mg/kg/day, which is approximately 54 times the MRHD on a mg/m 2 basis, respectively.
A reproduction study in rats revealed no evidence of harm to the fetus at oral doses up to 30 mg/kg/day, approximately 4-fold the MRHD on a mg/m 2 basis.
Adverse reactions
The following are discussed in more detail in other sections of the labeling: Abuse, Misuse, and Addiction [see Box Warning, Warnings and Precautions ( 5.1 ), and Drug Abuse and Dependence ( 9.2 , 9.3 )] Known hypersensitivity to methylphenidate or other ingredients [see Contraindications ( 4 )] Hypertensive crisis when used concomitantly with monoamine oxidase inhibitors [see Contraindications (4) and Drug Interactions ( 7.1 )] 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 )] Potential for Gastrointestinal Obstruction [see Warnings and Precautions ( 5.8 )] Acute Angle Closure Glaucoma [see Warnings and Precautions ( 5.9 )] Increased Intraocular Pressure and Glaucoma [see Warnings and Precautions ( 5.10 )] Motor and Verbal Tics, and Worsening of Tourette’s Syndrome [see Warnings and Precautions ( 5.11 )] The most common adverse reactions (>5%) were: Pediatric patients 6 to 17 years: abdominal pain upper ( 6.1 ) Adults: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Vertical Pharmaceuticals, LLC at 1-800-444-5164 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of RELEXXII for the treatment of ADHD is based on adequate and well-controlled studies of another formulation of methylphenidate hydrochloride extended-release tablets.
Below is a display of adverse reactions from those adequate and well-controlled studies in ADHD. Adults and pediatric patients 6 to 17 years with ADHD were evaluated in six controlled clinical studies and eleven open-label clinical studies (see Table 3). Safety was assessed by collecting adverse reactions, vital signs, weights, and electrocardiograms (ECGs), and by performing physical examinations and laboratory analyses.
A total of 3,906 patients participated in the clinical trials. Table 3: Exposure in Double-Blind and Open-Label Clinical Studies of Another Formulation of Methylphenidate Hydrochloride Extended-Release Tablets Patient Population N Dosage Range Pediatric patients 6 to 12 years 2216 18 mg to 54 mg once daily Pediatric patients 13 to 17 years 502 18 mg to 72 mg once daily Adults 1188 18 mg to 108 mg* once daily * 108 mg is 1.5 times the maximum recommended dosage of RELEXXII.
The most common adverse reactions in double-blind clinical trials (>5%) were: Pediatric patients 6 to 17 years: abdominal pain upper (see Table 4). Adults: decreased appetite, headache, dry mouth, nausea, insomnia, anxiety, dizziness, weight decreased, irritability, and hyperhidrosis (see Table 5). The most common adverse reactions associated with discontinuation (≥1%) from either pediatric or adult clinical trials were anxiety, irritability, insomnia, and blood pressure increased .
Adverse reactions in either the pediatric or adult double-blind adverse reactions tables may be relevant for both patient populations. Pediatric Patients 6 to 17 Years Table 4 lists the adverse reactions reported in 1% or more of another formulation of methylphenidate hydrochloride extended-release tablet-treated pediatric patients (6 to 17 years) in four placebo-controlled, double-blind clinical trials. Table 4: Adverse Reactions Reported by ≥1% of Pediatric Patients (6 to 17 years) Treated with Another Formulation of Methylphenidate Hydrochloride Extended-release Tablets in Four Placebo-Controlled, Double-Blind Clinical Trials System/Organ Class Adverse Reaction Another Formulation of Methylphenidate Hydrochloride Extended-release Tablets (n=321) % Placebo (n=318) % Gastrointestinal Disorders Abdominal pain upper 6.2
3.8 Vomiting 2.8
1.6 General Disorders and Administration Site Conditions Pyrexia 2.2
0.9 Infections and Infestations Nasopharyngitis 2.8
2.2Nervous System Disorders Dizziness 1.9 0 Psychiatric Disorders
Insomnia * 2.8
0.3 Respiratory, Thoracic and Mediastinal Disorders Cough 1.9
0.9 Oropharyngeal pain 1.2 0.9 * Terms of Initial insomnia (methylphenidate hydrochloride extended-release tablets =0.6%) and Insomnia (methylphenidate hydrochloride extended-release tablets =2.2%) are combined into Insomnia. Adults Table 5 lists the adverse reactions reported in 1% or more of adults treated with another formulation of methylphenidate hydrochloride extended-release tablets in two placebo-controlled, double-blind clinical trials.
Table 5: Adverse Reactions Reported by ≥1% of Adults Treated with Another Formulation of Methylphenidate Hydrochloride Extended-release Tablets in Two Placebo-Controlled, Double-Blind Clinical Trials * System/Organ Class Adverse Reaction Another Formulation of Methylphenidate Hydrochloride Extended-release Tablets (n=415) % Placebo (n=212) % Cardiac Disorders Tachycardia 4.8 0 Palpitations 3.1
0.9Ear and Labyrinth Disorders Vertigo 1.7 0 Eye Disorders
Vision blurred 1.7
0.5Gastrointestinal Disorders
Dry mouth 14.0
3.8 Nausea 12.8
3.3 Dyspepsia 2.2
0.9 Vomiting 1.7
0.5 Constipation 1.4
0.9 General Disorders and Administration Site Conditions Irritability 5.8
1.4Infections and Infestations
Upper respiratory tract infection 2.2
0.9Investigations
Weight decreased 6.5
3.3Metabolism and Nutrition Disorders
Decreased appetite 25.3
6.6Anorexia 1.7 0 Musculoskeletal and Connective Tissue Disorders
Muscle tightness 1.9 0 Nervous System Disorders Headache 22.2
15.6 Dizziness 6.7
5.2 Tremor 2.7
0.5Paresthesia 1.2 0 Sedation 1.2 0
Tension headache 1.2
0.5 Psychiatric Disorders Insomnia 12.3
6.1 Anxiety 8.2
2.4 Initial insomnia 4.3
2.8 Depressed mood 3.9
1.4 Nervousness 3.1
0.5 Restlessness 3.1 0 Agitation 2.2
0.5 Aggression 1.7
0.5 Bruxism 1.7
0.5 Depression 1.7
0.9 Libido decreased 1.7
0.5 Affect lability 1.4
0.9 Confusional state 1.2
0.5 Tension 1.2
0.5Respiratory, Thoracic and Mediastinal Disorders
Oropharyngeal pain 1.7
1.4Skin and Subcutaneous Tissue Disorders Hyperhidrosis 5.1
0.9 * Included doses up to 108 mg (1.5 times the maximum recommended dosage of RELEXXII). Adverse Reactions Observed in Clinical Trials with Another Formulation of Methylphenidate Hydrochloride Extended-release Tablets This section includes adverse reactions reported with use of another formulation of methylphenidate hydrochloride extended-release tablets in double-blind trials that do not meet the criteria specified for Table 4 or Table 5 and all adverse reactions reported by the other formulation of methylphenidate hydrochloride extended-release tablets-treated patients who participated in open-label and postmarketing clinical trials.
Blood and Lymphatic System Disorders: Leukopenia Eye Disorders: Accommodation disorder, Dry eye Vascular Disorders: Hot flush Gastrointestinal Disorders: Abdominal discomfort, Abdominal pain, Diarrhea General Disorders and Administrative Site Conditions: Asthenia, Fatigue, Feeling jittery, Thirst Infections and Infestations: Sinusitis Investigations: Alanine aminotransferase increased, Blood pressure increased, Cardiac murmur, Heart rate increased Musculoskeletal and Connective Tissue Disorders: Muscle spasms Nervous System Disorders: Lethargy, Psychomotor hyperactivity, Somnolence Psychiatric Disorders: Anger, Hypervigilance, Mood altered, Mood swings, Panic attack, Sleep disorder, Tearfulness, Tic Reproductive System and Breast Disorders: Erectile
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
METHYLPHENIDATE HYDROCHLORIDE 27MG
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
