Methylphenidate Hydrochloride (Page 4 of 5)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

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 (MRHD) of 60 mg/kg given to adults 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.

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/m2 basis.

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 Ames reverse mutation assay, in the in vitro mouse lymphoma cell forward mutation assay, or in the in vitro chromosomal aberration assay using human lymphocytes. 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. Methylphenidate was negative in vivo in males and females in the mouse bone marrow micronucleus assay.

Impairment 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/m2 basis.

16 HOW SUPPLIED/STORAGE AND HANDLING

Methylphenidate Hydrochloride Oral Solution is a clear, colorless to pale yellow, grape flavored solution with no visible particulates available in the following strengths

• 5 mg per 5 mL
Bottles of 500 mL………..NDC 71930-024-52

• 10 mg per 5 mL
Bottles of 500 mL……… NDC 71930-025-52

Storage and Handling
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in tight container with child-resistant closure.

Disposal
Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining, unused, or expired methylphenidate hydrochloride oral solution 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 methylphenidate hydrochloride oral solution 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 methylphenidate hydrochloride oral solution in the household trash.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Controlled Substance Status/High Potential for Abuse and Dependence
Advise patients that methylphenidate hydrochloride oral solution is a federally controlled substance, and it can be abused and lead to dependence [see Drug Abuse and Dependence (9.1, 9.2, and 9.3)]. Instruct patients that they should not give methylphenidate hydrochloride oral solution to anyone else. Advise patients to store methylphenidate hydrochloride oral solution in a safe place, preferably locked, to prevent abuse. Advise patients to comply with laws and regulations on drug disposal. Advise patients to dispose of remaining, unused, or expired methylphenidate hydrochloride oral solution by a medicine take-back program if available [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9), How Supplied/Storage and Handling (16)].

Serious Cardiovascular Risks
Advise patients that there is a potential serious cardiovascular risk including sudden death, myocardial infarction, and stroke with methylphenidate hydrochloride oral solution. 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 [see Warnings and Precautions (5.2)].

Blood Pressure and Heart Rate Increases

Instruct patients that methylphenidate hydrochloride oral solution can elevate blood pressure and heart rate [see Warnings and Precautions (5.3)].

Psychiatric Risks
Advise patients that methylphenidate hydrochloride oral solution, at recommended doses, can cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania [see Warnings and Precautions (5.4)].

Priapism
Advise patients of the possibility of painful or prolonged penile erections (priapism). Instruct the patient to seek immediate medical attention in the event of priapism [see Warnings and Precautions (5.5)].

Circulation Problems in Fingers and Toes (Peripheral Vasculopathy, Including Raynaud’s Phenomenon)
Instruct patients about the risk of peripheral vasculopathy, including Raynaud’s phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.

Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking methylphenidate hydrochloride oral solution. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients [see Warnings and Precautions (5.6)].

Suppression of Growth
Advise patients that methylphenidate hydrochloride oral solution may cause slowing of growth and weight loss in pediatric patients [see Warnings and Precautions (5.7)].

Pregnancy Exposure Registry
Inform patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in patients exposed to methylphenidate hydrochloride oral solution during pregnancy [see Use in Specific Populations (8.1)].

Distributed by:
Eywa Pharma Inc.
2 Research Way, Floor 3
Princeton, NJ 08540

Manufactured by:
WES Pharma Inc
Westminster, MD 21157

Revised: 08/2021

SPL MEDGUIDE SECTION

MEDICATION GUIDE Methylphenidate (METH-il-FEN-i-date) Hydrochloride Oral Solution
What is the most important information I should know about methylphenidate hydrochloride oral solution? Methylphenidate hydrochloride oral solution can cause serious side effects, including:Abuse and dependence. Methylphenidate hydrochloride oral solution, other methylphenidate containing medicines, and amphetamines have a high chance for abuse and can cause physical and psychological dependence. Your healthcare provider should check you or your child for signs of abuse and dependence before and during treatment with methylphenidate hydrochloride oral solution. o Tell your healthcare provider if you or your child have ever abused or been dependent on alcohol, prescription medicines, or street drugs. o Your healthcare provider can tell you more about the differences between physical and psychological dependence and drug addiction.• Heart-related problems, including: o sudden death, stroke, and heart attack in adults o sudden death in children who have heart problems or heart defects o increased blood pressure and heart rateYour healthcare provider should check you or your child carefully for heart problems before starting treatment with methylphenidate hydrochloride oral solution. Tell your healthcare provider if you or your child have any heart problems, heart defects, high blood pressure, or have a family history of these problems. Your healthcare provider should check your or your child’s blood pressure and heart rate regularly during treatment with methylphenidate hydrochloride oral solution. Call your healthcare provider 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 methylphenidate hydrochloride oral solution. • Mental (psychiatric) problems, including: o new or worse behavior and thought problems o new or worse bipolar illness o new psychotic symptoms (such as hearing voices, or seeing or believing things that are not real) or new manic symptomsTell 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 methylphenidate hydrochloride oral solution, especially hearing voices, seeing or believing things that are not real, or new manic symptoms.
What is methylphenidate hydrochloride oral solution? Methylphenidate hydrochloride oral solution is a prescription medicine used for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in people 6 years of age and older. Methylphenidate hydrochloride oral solution may help increase attention and decrease impulsiveness and hyperactivity in people with ADHD. It is not known if methylphenidate hydrochloride oral solution is safe and effective for use in children under 6 years of age.Methylphenidate hydrochloride oral solution is a federally controlled substance (CII) because it contains methylphenidate that can be a target for people who abuse prescription medicines or street drugs. Keep methylphenidate hydrochloride oral solution in a safe place to protect it from theft. Never give your methylphenidate hydrochloride oral solution to anyone else because it may cause death or harm them. Selling or giving away methylphenidate hydrochloride oral solution may harm others and is against the law.
Do not take methylphenidate hydrochloride oral solution if you or your child are: • allergic to methylphenidate hydrochloride or any of the ingredients in methylphenidate hydrochloride oral solution. See the end of this Medication Guide for a complete list of ingredients in methylphenidate hydrochloride oral solution. • taking, or have stopped taking within the past 14 days, a medicine called a monoamine oxidase inhibitor (MAOI).
Before taking methylphenidate hydrochloride oral solution tell your healthcare provider about all your medical conditions, including if you or your child: • have heart problems, 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 and toes • are pregnant or plan to become pregnant. It is not known if methylphenidate hydrochloride oral solution will harm the unborn baby. o There is a pregnancy registry for females who are exposed to methylphenidate hydrochloride oral solution during pregnancy. The purpose of the registry is to collect information about the health of females exposed to methylphenidate hydrochloride oral solution and their baby. If you or your child becomes pregnant during treatment with methylphenidate hydrochloride oral solution, talk to your healthcare provider about registering with the National Pregnancy Registry for Psychostimulants at 1-866-961-2388. • are breastfeeding or plan to breastfeed. Methylphenidate hydrochloride oral solution passes into breast milk. Talk to your healthcare provider about the best way to feed the baby during treatment with methylphenidate hydrochloride oral solution. Tell your healthcare provider about all the medicines that you take or your child take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.Methylphenidate hydrochloride oral solution and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be changed during treatment with methylphenidate hydrochloride oral solution. Your healthcare provider will decide whether methylphenidate hydrochloride oral solution can be taken with other medicines.Especially tell your healthcare provider if you or your child take a medicine used to treat depression called a monoamine oxidase inhibitor (MAOI).Know the medicines that you take or your child take. Keep a list of your medicines with you to show your healthcare provider and pharmacist. Do not start any new medicine during treatment with methylphenidate hydrochloride oral solution without talking to your healthcare provider first.
How should methylphenidate hydrochloride oral solution be taken? Take methylphenidate hydrochloride oral solution exactly as prescribed by your healthcare provider. • Your healthcare provider may change the dose if needed. • Children 6 years of age and older: o Take methylphenidate hydrochloride oral solution by mouth 2 times a day before breakfast and lunch, 30 to 45 before a meal, as prescribed by your healthcare provider. • Adults: o Take methylphenidate hydrochloride oral solution by mouth 2 or 3 times a day, 30 to 45 before a meal, as prescribed by your healthcare provider. o For adults who have sleep problems when methylphenidate hydrochloride oral solution is taken late in the day, take your last dose of methylphenidate hydrochloride oral solution before 6 p.m. • Your healthcare provider may sometimes stop methylphenidate hydrochloride oral solution treatment for a while to check ADHD symptoms. • If you or your child take too much methylphenidate hydrochloride oral solution, call your poison control center at 1-800-222-1222 or go to the nearest hospital emergency room right away.
What are the possible side effects of methylphenidate hydrochloride oral solution? Methylphenidate hydrochloride oral solution can cause serious side effects, including: • See “What is the most important information I should know about methylphenidate hydrochloride oral solution? ” • Painful and prolonged erections (priapism). Priapism has happened in males who take products that contain methylphenidate. If you or your child develop priapism, get medical help right away.Circulation problems in fingers and toes (peripheral vasculopathy, including Raynaud’s phenomenon). Signs and symptoms may include: o fingers or toes may feel numb, cool, painful o fingers or toes may change color from pale, to blue, to redTell 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 methylphenidate hydrochloride oral solution.• Slowing of growth (height and weight) in children. Children should have their height and weight checked often during treatment with methylphenidate hydrochloride oral solution. methylphenidate hydrochloride oral solution treatment may be stopped if your child is not growing or gaining weight.
The most common side effects of methylphenidate hydrochloride oral solution include: • increased heart rate • irregular heart beat (palpitations) • headache • trouble sleeping • anxiety • sweating • weight loss • decreased appetite • dry mouth • nausea • stomach pain These are not all the possible side effects of methylphenidate hydrochloride oral solution.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 methylphenidate hydrochloride oral solution? • Store methylphenidate hydrochloride oral solution at room temperature between 68°F to 77°F (20°C to 25°C). Store methylphenidate hydrochloride oral solution in a safe place, like a locked cabinet. • Protect from light and moisture. • Dispose of remaining, unused, or expired methylphenidate hydrochloride oral solution by a medication take-back program at authorized collection sites such as retail pharmacies, hospital or clinic pharmacies, and law enforcement locations. If no take-back program or authorized collector is available, mix methylphenidate hydrochloride oral solution 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 methylphenidate hydrochloride oral solution in the household trash.Keep methylphenidate hydrochloride oral solution and all medicines out of the reach of children.
General information about the safe and effective use of methylphenidate hydrochloride oral solution. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use methylphenidate hydrochloride oral solution for a condition for which it was not prescribed. Do not give methylphenidate hydrochloride oral solution to other people, even if they have the same symptoms. It may harm them and it is against the law. You can ask your healthcare provider or pharmacist for information about methylphenidate hydrochloride oral solution that was written for healthcare professionals. For more information, please contact WES Pharma Inc at 1-888-212-6921.
What are the ingredients in methylphenidate hydrochloride oral solution? Active Ingredient: methylphenidate hydrochloride USPInactive Ingredients: glycerin, polyethylene glycol 1450, concord grape flavor N&A, diluted hydrochloric acid (10%), and purified water.
Distributed by: Eywa Pharma Inc. 2 Research Way, Floor 3 Princeton, NJ 08540 Manufactured by: WES Pharma Inc Westminster, MD 21157
This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 8/2021

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