DRUGS & SUPPLEMENTS
GenRx Methylphenidate uses
WARNING: ABUSE AND DEPENDENCE
CNS stimulants, including GenRx Methylphenidate, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy .
WARNING: ABUSE AND DEPENDENCE
See full prescribing information for complete boxed warning.
1 INDICATIONS AND USAGE
GenRx Methylphenidate is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 17 years of age .
GenRx Methylphenidate is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in pediatric patients 6 to 17 years of age. (1)
2 DOSAGE AND ADMINISTRATION
2.1 Pretreatment Screening
Prior to initiating treatment with GenRx Methylphenidate, assess for the presence of cardiac disease (i.e. perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) .
Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Maintain careful prescription records, educate patients about abuse, and periodically re-evaluate the need for GenRx Methylphenidate use .
2.2 General Dosing Information
GenRx Methylphenidate is given orally once daily in the morning.
Advise patients to take GenRx Methylphenidate consistently either with food or without food .
The recommended starting dose of GenRx Methylphenidate for patients 6 to 17 years of age is 17.3 mg once daily in the morning. The dose may be titrated weekly in increments of 8.6 mg to 17.3 mg. Daily doses above 51.8 mg have not been studied and are not recommended.
The dose should be individualized according to the needs and responses of the patient.
Pharmacological treatment of ADHD may be needed for extended periods. Periodically re-evaluate the long-term use of GenRx Methylphenidate and adjust dosage as needed.
2.3 Dose Reduction and Discontinuation
If paradoxical aggravation of symptoms or other adverse effects occur, reduce dosage, or, if necessary, discontinue the drug. GenRx Methylphenidate should be periodically discontinued to assess the child's condition. If improvement is not observed after appropriate dosage adjustment over a one-month period, discontinue the drug.
2.4 COTEMPLA XR-ODT Administration
Instruct the patient or caregiver on the following administration instructions:
3 DOSAGE FORMS AND STRENGTHS
Extended-Release Orally Disintegrating Tablets: 8.6 mg, 17.3 mg and 25.9 mg. (3)
GenRx Methylphenidate is contraindicated in patients with:
5 WARNINGS AND PRECAUTIONS
5.1 Potential for Abuse and Dependence
CNS stimulants, including GenRx Methylphenidate, other methylphenidate-containing products, and amphetamines, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy .
5.2 Serious Cardiovascular Reactions
Sudden death, stroke and myocardial infarction have occurred in adults treated with CNS stimulants at recommended doses. Sudden death has occurred in pediatric patients with structural cardiac abnormalities and other serious cardiac problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, and other serious heart problems. Perform further evaluation on patients who develop exertional chest pain, unexplained syncope, or arrhythmias during GenRx Methylphenidate treatment.
5.3 Blood Pressure and Heart Rate Increases
CNS stimulants cause an increase in blood pressure and heart rate (mean increase approximately 3 to 6 bpm). Individuals may have larger increases. Monitor all patients for hypertension and tachycardia.
5.4 Psychiatric Adverse Reactions
Exacerbation 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 Disorder
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. If such symptoms occur, consider discontinuing GenRx Methylphenidate. 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 in placebo-treated patients.
Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with GenRx 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. Patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention.
5.6 Peripheral Vasculopathy, including Raynaud's Phenomenon
CNS stimulants, including GenRx Methylphenidate, 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.
5.7 Long-Term Suppression of Growth
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 GenRx 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 consistently medicated children (i.e. treatment for 7 days per week throughout the year) have 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 period of development.
Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including GenRx Methylphenidate. Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.
6 ADVERSE REACTIONS
The following are discussed in more detail in other sections of the labeling:
Based on accumulated data from other GenRx Methylphenidate products, the most common (>5% and twice the rate of placebo) adverse reactions are appetite decreased, insomnia, nausea, vomiting, dyspepsia, abdominal pain, weight decreased, anxiety, dizziness, irritability, affect lability, tachycardia, and blood pressure increased. (6)
To report SUSPECTED ADVERSE REACTIONS, contact Neos Therapeutics, Inc. at 1-888-319-1789 or http://www. COTEMPLAXRODT.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trial 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 the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical Trials Experience with Other GenRx Methylphenidate Products in Children, Adolescents, and Adults with ADHD
Commonly reported (≥2% of the GenRx Methylphenidate group and at least twice the rate of the placebo group) adverse reactions from placebo-controlled trials of GenRx Methylphenidate products include: appetite decreased, weight decreased, nausea, abdominal pain, dyspepsia, dry mouth, vomiting, insomnia, anxiety, nervousness, restlessness, affect lability, agitation, irritability, dizziness, vertigo, tremor, blurred vision, blood pressure increased, heart rate increased, tachycardia, palpitations, hyperhidrosis, and pyrexia.
Clinical Trials Experience with GenRx Methylphenidate in Children with ADHD
There is limited experience with GenRx Methylphenidate in controlled trials. Based on this limited experience, the adverse reaction profile of GenRx Methylphenidate appears similar to other GenRx Methylphenidate extended release-products.
6.2 Postmarketing Experience
The following adverse reactions have been identified during post approval use of GenRx Methylphenidate products. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are as follows:
Blood and Lymphatic System Disorders: Pancytopenia, Thrombocytopenia, Thrombocytopenic purpura
Cardiac Disorders: Angina pectoris, Bradycardia, Extrasystole, Supraventricular tachycardia, Ventricular extrasystole
Eye Disorders: Diplopia, Mydriasis, Visual impairment
General Disorders: Chest pain, Chest discomfort, Hyperpyrexia
Immune System Disorders: Hypersensitivity reactions such as Angioedema, Anaphylactic reactions, Auricular swelling, Bullous conditions, Exfoliative conditions, Urticarias, Pruritis NEC, Rashes, Eruptions, and Exanthemas NEC
Investigations: Alkaline phosphatase increased, Bilirubin increased, Hepatic enzyme increased, Platelet count decreased, White blood cell count abnormal
Musculoskeletal, Connective Tissue and Bone Disorders: Arthralgia, Myalgia, Muscle twitching, Rhabdomyolysis
Nervous System Disorders: Convulsion, Grand mal convulsion, Dyskinesia, Serotonin syndrome in combination with serotonergic drugs
Psychiatric Disorders: Disorientation, Hallucination, Hallucination auditory, Hallucination visual, Libido changes, Mania
Urogenital System: Priapism
Skin and Subcutaneous Tissue Disorders: Alopecia, Erythema
Vascular Disorders: Raynaud's phenomenon
7 DRUG INTERACTIONS
7.1 Clinically Important Interactions with GenRx Methylphenidate
8 USE IN SPECIFIC POPULATIONS
Pregnancy Exposure Registry
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to GenRx Methylphenidate during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388.
Published studies and postmarketing reports on GenRx Methylphenidate use during pregnancy are insufficient to inform a drug-associated risk of adverse pregnancy-related outcomes . There are risks to the fetus associated with the use of central nervous system stimulants during pregnancy . No teratogenic effects were observed in embryo-fetal development studies with oral administration of GenRx Methylphenidate to pregnant rats and rabbits during organogenesis at doses 4 and 18 times, respectively, the maximum recommended human dose (MRHD) of 51.8 mg (as base). However, spina bifida was observed in rabbits at a dose 60 times the MRHD .
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 2-4% and 15-20%, respectively.
Fetal/Neonatal adverse reactions
CNS stimulants, such as GenRx Methylphenidate, 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 GenRx Methylphenidate during pregnancy; however, premature delivery and low birth weight infants have been reported in amphetamine-dependent mothers.
A limited number of pregnancies have been reported in published observational studies and postmarketing reports describing GenRx Methylphenidate use during pregnancy. Due to the small number of methylphenidate-exposed pregnancies with known outcomes, these data cannot definitely establish or exclude any drug-associated risk during pregnancy. Methodological limitations of these observational studies include small sample size, concomitant use of other medications, lack of detail regarding dose and duration of exposure to GenRx Methylphenidate and non-generalizability of the enrolled populations.
In studies conducted in rats and rabbits, GenRx Methylphenidate was administered orally at doses of up to 75 and 200 mg/kg/day, respectively, during the period of organogenesis. Teratogenic effects (increased incidence of fetal spina bifida) were observed in rabbits at the highest dose, which is approximately 60 times the maximum recommended human dose (MRHD) of 51.8 mg (as base) for adolescents on a mg/m2 basis. The no effect level for embryo-fetal development in rabbits was 60 mg/kg/day (18 times the MRHD for adolescent on a mg/m2 basis). There was no evidence of specific teratogenic activity in rats, although increased incidences of fetal skeletal variations were seen at the highest dose level (11 times the MRHD on a mg/m2 basis for adolescent), 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/m2 basis for adolescent).
Limited published literature, based on breast milk sampling from five mothers, reports that GenRx Methylphenidate is present in human milk, which resulted in infant doses of 0.16% to 0.7% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.1 and 2.7. 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 GenRx Methylphenidate and any potential adverse effects on the breastfed child from GenRx Methylphenidate or from the underlying maternal condition.
Monitor breastfeeding infants for adverse reactions, such as agitation, insomnia, anorexia, and reduced weight gain.
8.4 Pediatric Use
The safety and effectiveness of GenRx Methylphenidate have been established in pediatric patients 6 to 17 years of age in one adequate and well-controlled study in pediatric patients 6 to 12 years, pharmacokinetic data in adolescents, and safety information from other methyphenidate-containing products .
The long-term efficacy of GenRx Methylphenidate in pediatric patients has not been established. Safety and effectiveness of GenRx Methylphenidate in pediatric patients below 6 years of age have not been established.
Long Term Suppression Growth
Growth should be monitored during treatment with stimulants, including GenRx Methylphenidate. Children who are not growing or gaining weight as expected may need to have their treatment interrupted .
Juvenile Animal Toxicity Data
Rats treated with GenRx Methylphenidate early in the postnatal period through sexual maturation demonstrated a decrease in spontaneous locomotor activity in adulthood. A deficit in acquisition of a specific learning task was observed in females only. The doses at which these findings were observed are at least 6 times the maximum recommended human dose (MRHD) of 51.8 mg (as base) for pediatric patients on a mg/m2 basis.
In the study conducted in young rats, GenRx 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 13-14), decreased spontaneous locomotor activity was observed in males and females previously treated with 50 mg/kg/day [approximately 6 times the MRHD of 51.8 mg (as base) on a mg/m2 basis] or greater, and a deficit in the acquisition of a specific learning task was observed in females exposed to the highest dose (12 times the MRHD on a mg/m2 basis). The no effect level for juvenile neurobehavioral development in rats was 5 mg/kg/day (half the MRHD on a mg/m2 basis). The clinical significance of the long-term behavioral effects observed in rats is unknown.
8.5 Geriatric Use
GenRx Methylphenidate has not been studied in patients over the age of 65 years.
9 DRUG ABUSE AND DEPENDENCE
9.1 Controlled Substance
GenRx Methylphenidate contains GenRx Methylphenidate, a Schedule II controlled substance.
CNS stimulants including GenRx Methylphenidate, other methylphenidate-containing products, and amphetamines have a high potential for abuse. Abuse is characterized by impaired control over drug use, compulsive use, continued use despite harm, and craving.
Signs and symptoms of CNS stimulant abuse include increased heart rate, respiratory rate, blood pressure, and/or sweating, dilated pupils, hyperactivity, restlessness, insomnia, decreased appetite, loss of coordination, tremors, flushed skin, vomiting, and/or abdominal pain. Anxiety, psychosis, hostility, aggression, suicidal or homicidal ideation have also been observed. Abusers of CNS stimulants may chew, snort, inject, or use other unapproved routes of administration which can result in overdose and death .
To reduce the abuse of CNS stimulants including GenRx Methylphenidate, assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records educate patients and their families about abuse and on proper storage and disposal of CNS stimulants , monitor for signs of abuse while on therapy, and re-evaluate the need for GenRx Methylphenidate use.
Tolerance (a state of adaptation in which exposure to a drug results in a reduction of the drug's desired and/or undesired effects over time) can occur during chronic therapy with CNS stimulants including GenRx Methylphenidate.
Physical dependence (a state of adaptation manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist) can occur in patients treated with CNS stimulants including GenRx Methylphenidate. Withdrawal symptoms after abrupt cessation following prolonged high-dosage administration of CNS stimulants include dysphoric mood; depression, fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.
10.1 Signs and Symptoms
Signs and symptoms of acute GenRx Methylphenidate overdosage, resulting principally from overstimulation of the CNS and from excessive sympathomimetic effects, may include the following: nausea, vomiting, diarrhea, restlessness, anxiety, agitation, tremors, hyperflexia, muscle twitching, convulsion, euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, hypotension, tachypnea, mydriasis, dryness of mucous membranes, and rhabdomyolysis.
10.2 Management of Overdose
Consult with a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice on the management of overdosage with GenRx Methylphenidate. Provide supportive care, including close medical supervision and monitoring. Treatment should consist of general measures employed in the management of overdosage with any drug. Consider the possibility of multiple drug overdosage. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. Use supportive and symptomatic measures.
GenRx Methylphenidate contains GenRx Methylphenidate, a central nervous system (CNS) stimulant. GenRx Methylphenidate is an extended-release orally disintegrating tablet intended for once daily administration. GenRx Methylphenidate contains approximately 25% immediate-release and 75% extended-release GenRx Methylphenidate. GenRx Methylphenidate is ionically-bound to the sulfonate of polystyrene sulfonate particles.
GenRx Methylphenidate contains 8.6 mg, 17.3 mg or 25.9 mg of GenRx Methylphenidate which is the same as the amount of GenRx Methylphenidate (base equivalent) found, respectively, in 10 mg, 20 mg and 30 mg strength GenRx Methylphenidate hydrochloride products.
The chemical name of GenRx Methylphenidate is methyl α-phenyl-2-piperidineacetate, and its structural formula is shown in Figure 1.
Figure 1: Methylphenidate Structure
C14H19NO2 Mol. Wt. 233.31
GenRx Methylphenidate also contains the following inactive ingredients: Mannitol, Fructose, Microcrystalline Cellulose, Crospovidone, Methacrylic Acid, Polystyrene Sulfonate, Citric Acid, Colloidal Silicon Dioxide, Grape Flavor, Natural Masking Type Powder, Triethyl Citrate, Magnesium Stearate, Ethylcellulose, Sucralose, Lake Blend Purple, and Polyethylene Glycol.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
GenRx Methylphenidate is a central nervous system stimulant. The mode of therapeutic action in ADHD is not known.
GenRx Methylphenidate is a racemic mixture comprised of the d- and 1-isomers. The d-isomer is more pharmacologically active than the l-isomer. GenRx 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.
After oral administration of GenRx Methylphenidate, circulation levels of l- GenRx Methylphenidate (MPH) were about 2% of total MPH.
Following a single dose of 51.8 mg (2×25.9 mg daily) GenRx Methylphenidate in healthy adult subjects under fasted conditions, plasma GenRx Methylphenidate (MPH) reached maximal concentration (Cmax) at a median time of 5 hours after dosing. Compared to an extended release capsule formulation of GenRx Methylphenidate, GenRx Methylphenidate mean Cmax and exposure (AUCinf) was about 26% and 6% higher, respectively, after GenRx Methylphenidate administration (Figure 2).
Figure 2: Mean d-GenRx Methylphenidate Plasma Concentration-Time Profiles After Administration of GenRx Methylphenidate or GenRx Methylphenidate Hydrochloride Extended-Release Capsule in Healthy Volunteers Under Fasted Conditions
Effect of Food
Administration of 51.8 mg GenRx Methylphenidate with food (a high fat meal) decreased the Cmax and increased AUCinf of total MPH by approximately 24% and 16%, respectively. Food shortened the median time to peak concentration (Tmax) by 0.5 hour (fed: 4.5 hours vs. fasted: 5.0 hours).
Effect of Alcohol
There is no in vivo study conducted for the effect of alcohol on drug exposure. An in vitro dissolution study showed alcohol-induced dose dumping potential in the presence of 40% alcohol. Dose dumping was not observed in the presence of lower alcohol concentrations.
Plasma GenRx Methylphenidate concentrations decline monophasically following oral administration of GenRx Methylphenidate. The mean plasma terminal elimination half-life of GenRx Methylphenidate was about 4 hours in healthy volunteers following a single 51.8 mg dose administration.
In humans, GenRx Methylphenidate is metabolized primarily via deesterification to alpha-phenyl-piperidine acetic acid (ritalinic acid). The metabolite has little or no pharmacological activity.
After oral dosing of radiolabeled GenRx Methylphenidate in humans, about 90% of the radioactivity was recovered in urine. The main primary metabolite was PPAA, accounting for approximately 80% of the dose.
Male and Female Patients and Ethnic Groups
There is insufficient experience with the use of GenRx Methylphenidate to detect gender or ethnic variations in pharmacokinetics.
The pharmacokinetics of GenRx Methylphenidate after GenRx Methylphenidate administration were studied in pediatric patients (6-17 years of age) with ADHD under fasted conditions. After a single oral dose of 51.8 mg GenRx Methylphenidate, plasma concentrations of GenRx Methylphenidate in children (6-12 years of age) were approximately twice the concentrations observed in adults. Exposure levels in adolescent patients (13 -17 years of age) were similar to those in adults. Body weight normalized clearance values were similar across the age groups (Table 2).
Patients with Renal Impairment
There is no experience with the use of GenRx Methylphenidate in patients with renal insufficiency. After oral administration of radiolabeled GenRx Methylphenidate in humans, GenRx Methylphenidate was extensively metabolized and approximately 80% of the radioactivity was excreted in the urine in the form of PPAA. Since renal clearance is not an important route of GenRx Methylphenidate clearance, renal insufficiency is expected to have little effect on the pharmacokinetics of GenRx Methylphenidate.
Patients with Hepatic Impairment
There is no experience with the use of GenRx Methylphenidate in patients with hepatic insufficiency.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
In a lifetime carcinogenicity study carried out in B6C3F1 mice, GenRx 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. For pediatric patients, this dose is approximately 4 times the maximum recommended human dose of 51.8 (as base) on a mg/m2 basis. 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.
GenRx 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 5 times the maximum recommended dose of 51.8 mg (as base) for pediatric patients on a mg/m2 basis.
GenRx Methylphenidate was not mutagenic in the in vitro Ames reverse mutation assay or 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. GenRx Methylphenidate was negative in an in vivo mouse bone marrow micronucleus assay.
Impairment of Fertility
GenRx 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 12-fold the maximum recommended human dose of 51.8 (as base) for adolescents on a mg/m2 basis.
14 CLINICAL STUDIES
The efficacy of GenRx Methylphenidate was evaluated in a laboratory classroom study conducted in 87 pediatric patients (Aged 6 to 12 years) with ADHD. Following washout of previous GenRx Methylphenidate medication, there was an open-label dose-optimization period (4 weeks) with an initial dose of 17.3 mg of GenRx Methylphenidate once daily in the morning. The dose could be titrated on a weekly basis from 17.3 mg, to 25.9 mg, to 34.6 mg, and up to 51.8 mg until an optimal dose or the maximum dose of 51.8 mg/day was reached. At the end of this period, subjects remained on their optimized dose for an additional week. Subjects then entered a 1-week randomized, double-blind, parallel group treatment period with the individually optimized dose of GenRx Methylphenidate or placebo. At the end of this week, raters evaluated the attention and behavior of the subjects in a laboratory classroom setting, using the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale SKAMP is a validated 13-item teacher-rated scale that assesses manifestations of ADHD in a classroom setting.
The primary efficacy endpoint was the average of the SKAMP-Combined (Attention and Deportment) scores over the test day (not including the baseline score), with assessments conducted at baseline, and 1, 3, 5, 7, 10, 12, and 13 hours post-dosing. The key secondary efficacy endpoints were onset and duration of effect, defined as the first point at which active drug separated from placebo on SKAMP-Combined scores and the last time point at which active drug separated from placebo on SKAMP-Combined scores, respectively.
The SKAMP-Combined scores test day average was statistically significantly lower (improved) with GenRx Methylphenidate compared to placebo (difference of -11 (95% CI: -13.9, -8.2)) (Table 3).
The SKAMP-Combined scores were also statistically significantly lower (improved) at time points (1, 3, 5, 7, 10, 12 hours) post-dosing with GenRx Methylphenidate compared to placebo (Figure 3).
Figure 3: LS Mean SKAMP Combined Score After Treatment with GenRx Methylphenidate or Placebo During Classroom Day in Patients with ADHD
*SE = Standard Error
The database was not large enough to assess whether there were differences in effects in age, gender, or race subgroups.
16 HOW SUPPLIED/STORAGE AND HANDLING
GenRx Methylphenidate Extended Release Orally Disintegrating Tablets are available in three strengths:
They are available as follows:
Store at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F).
Store GenRx Methylphenidate blister packages in the reusable travel case after removal from the carton.
Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining, unused, or expired GenRx Methylphenidate by a medicine take-back program or by an authorized collector registered with the Drug Enforcement Administration. If no take-back program or authorized collector is available, mix GenRx Methylphenidate with an undesirable, nontoxic substance to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and discard GenRx Methylphenidate in the household trash.
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Controlled Substance Status/Potential for Abuse and Dependence
Advise patients and their caregivers that GenRx Methylphenidate is a federally controlled substance, and it can be abused or lead to dependence . Instruct patients that they should not give GenRx Methylphenidate to anyone else. Advise patients to store GenRx Methylphenidate in a safe place, preferably locked, to prevent abuse. Advise patients and their caregivers to comply with laws and regulations on drug disposal. Advise patients and their caregivers to dispose of remaining, unused, or expired GenRx Methylphenidate through a medicine take-back program if available .
Instructions for Taking GenRx Methylphenidate
Instruct patients and their caregivers on the following:
Serious Cardiovascular Risks
Advise patients, caregivers, and their family members that there is a potential for serious cardiovascular risks including sudden death, myocardial infarction, and stroke with GenRx Methylphenidate. Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease .
Blood Pressure and Heart Rate Increases
Advise patients and their caregivers that GenRx Methylphenidate can elevate blood pressure and heart rate .
Advise patients and their caregivers that GenRx Methylphenidate, at recommended doses, can cause psychotic or manic symptoms, even in patients without a prior history or psychotic symptoms or mania .
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]
Suppression of Growth
Advise patients, families, and caregivers that GenRx Methylphenidate can cause slowing of growth and weight loss .
Advise patients to avoid alcohol while taking GenRx Methylphenidate. Consumption of alcohol while taking GenRx Methylphenidate may result in a more rapid release of the dose of GenRx Methylphenidate .
Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to GenRx Methylphenidate during pregnancy .
Manufactured for Neos Therapeutics Brands, LLC. Grand Prairie, TX 75050. Made in USA.
For more information, call 1-(888)-319-1789
GenRx Methylphenidate is a registered trademark of Neos Therapeutics, Inc.
Copyright© 2014, Neos Therapeutics, Inc.
Item # PIN010299
GenRx Methylphenidate pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
GenRx Methylphenidate available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
GenRx Methylphenidate destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
GenRx Methylphenidate Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
GenRx Methylphenidate pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming GenRx Methylphenidate?
Depending on the reaction of the GenRx Methylphenidate after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider GenRx Methylphenidate not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is GenRx Methylphenidate addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Reviewsdrugs.com conducted a study on GenRx Methylphenidate, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of GenRx Methylphenidate consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Visitor reported usefulNo survey data has been collected yet
Visitor reported side effectsNo survey data has been collected yet
Visitor reported price estimatesNo survey data has been collected yet
Visitor reported frequency of useNo survey data has been collected yet
Visitor reported dosesNo survey data has been collected yet
Visitor reported time for resultsNo survey data has been collected yet
Visitor reported administrationNo survey data has been collected yet
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The information was verified by Dr. Arunabha Ray, MD Pharmacology