Methylphenidate

The area selected should not be oily, damaged, or irritated. Apply methylphenidate transdermal system to the hip area avoiding the waistline, since clothing may cause the transdermal system to rub off. When applying the transdermal system the next morning, place on the opposite hip at a new site if possible.

If patients or caregivers experience difficulty separating the transdermal system from the release liner or observe transfer of adhesive to the liner, tearing and/or other damage to the transdermal system during removal from the liner, the transdermal system should be discarded and a new transdermal system should be applied.

Patients or caregivers should inspect the release liner to ensure that no adhesive containing medication has transferred to the liner. If adhesive transfer has occurred, the transdermal system should be discarded. Refer to the Instructions for Use for recommendations for discarding used methylphenidate transdermal systems.

Methylphenidate transdermal system should be applied immediately after opening the individual pouch and removing the protective liner. Do not use if the individual pouch seal is broken or if the transdermal system appears to be damaged.

Do not cut transdermal systems. Only intact transdermal systems should be applied. The transdermal system should then be pressed firmly in place with the palm of the hand for approximately 30 seconds, making sure that there is good contact of the transdermal system with the skin, especially around the edges.

Exposure to water during bathing, swimming, or showering can affect transdermal system adherence. Methylphenidate transdermal systems should not be applied or re-applied with dressings, tape, or other common adhesives. In the event that a transdermal system does not fully adhere to the skin upon application, or becomes partially or fully detached during wear time, the transdermal system should be discarded and a new transdermal system may be applied at a different site.

The total recommended wear time for that day should remain 9 hours regardless of the number of transdermal systems used. 10) ] . When heat is applied to methylphenidate transdermal system after transdermal system application, both the rate and the extent of absorption are significantly increased.

3) ] . This increased absorption can be clinically significant and result in overdose of methylphenidate [see Overdosage (10) ] . Methylphenidate transdermal systems should not be stored in refrigerators or freezers. 4 Removal of Methylphenidate Transdermal System Methylphenidate transdermal systems should be peeled off slowly.

, petroleum jelly, olive oil, or mineral oil) to the transdermal system edges, gently working the oil underneath the transdermal system edges. If any adhesive remains on the skin following transdermal system removal, an oil-based product may be applied to transdermal system sites in an effort to gently loosen and remove any residual adhesive that remains following transdermal system removal.

In the unlikely event that a transdermal system remains tightly adhered despite these measures, the patient or caregiver should contact the physician or pharmacist. , nail polish remover) should not be used to remove methylphenidate transdermal systems or adhesive.

5 Dose/Wear Time Reduction and Discontinuation Methylphenidate transdermal system may be removed earlier than 9 hours if a shorter duration of effect is desired or late day side effects appear. Plasma concentrations of d -methylphenidate generally begin declining when the transdermal system is removed, although absorption may continue for several hours.

Individualization of wear time may help manage some of the side effects caused by methylphenidate. If aggravation of symptoms or other adverse events occur, the dosage or wear time should be reduced, or, if necessary, the drug should be discontinued.

Residual methylphenidate remains in used transdermal systems when worn as recommended.

5 cm 2 , with a wear time of 9 hours. In the data presented below, the adverse reactions reported during exposure were obtained primarily by general inquiry at each visit, and were recorded by the clinical investigators using terminology of their own choosing.

Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of events into a smaller number of standardized event categories.

2% (1/85) receiving placebo. The most commonly reported (≥ 1% and twice the rate of placebo) adverse reactions leading to discontinuation in the methylphenidate transdermal system group were application site reaction (2%), tics (1%), headache (1%), and irritability (1%).

8% (2/72) receiving placebo. 4%). Commonly Observed Adverse Reactions in Double-Blind, Placebo-Controlled Trials Skin Irritation and Application Site Reactions Methylphenidate transdermal system is a dermal irritant. In addition to the most commonly reported adverse reactions presented in Table 2, the majority of subjects in those studies had minimal to definite skin erythema at the methylphenidate transdermal system application site.

This erythema generally caused no or minimal discomfort and did not usually interfere with therapy or result in discontinuation from treatment. Erythema is not by itself a manifestation of contact sensitization. 10) ] . Most Commonly Reported Adverse Reactions Table 2 lists treatment-emergent adverse reactions reported in ≥ 1% methylphenidate transdermal system-treated children or adolescents with ADHD in two 7 week double-blind, parallel-group, placebo-controlled studies conducted in the outpatient setting.

6% of adolescents experienced at least 1 adverse event. 1) Adverse Reactions in Studies with the Long-Term Use of Methylphenidate Transdermal System In a long-term open-label study of up to 12 months duration in 326 children wearing methylphenidate transdermal system 9 hours daily, the most common (≥ 10%) adverse reactions were decreased appetite, headache, and weight decreased.

7%) discontinued treatment as the result of an application site reaction. 5%) was the only additional adverse reaction leading to discontinuation reported with a frequency of greater than 1%. In a long-term open-label study of up to 6 months duration in 162 adolescents wearing methylphenidate transdermal system 9 hours daily, the most common (≥ 10%) adverse reactions were decreased appetite and headache.

9%) discontinued treatment as the result of an application site reaction. 2%). 2 Postmarketing Experience In addition, the following adverse reactions have been identified during the post-approval use of methylphenidate transdermal system.

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 methylphenidate transdermal system exposure. Cardiac Disorders: palpitations.

Eye Disorders: visual disturbances, blurred vision, increased intraocular pressure, mydriasis, and accommodation disorder. General Disorders and Administration Site Disorders: fatigue, application site reactions such as bleeding, bruising, burn, burning, dermatitis, discharge, discoloration, discomfort, dryness, eczema, edema, erosion, erythema, excoriation, exfoliation, fissure, hyperpigmentation, hypopigmentation, induration, infection, inflammation, irritation, pain, papules, paresthesia, pruritus, rash, scab, swelling, ulcer, urticaria, vesicles, and warmth.

Immune System Disorders: hypersensitivity reactions including generalized erythematous and urticarial rashes, allergic contact dermatitis, angioedema, and anaphylaxis. Investigations: blood pressure increased. Nervous System Disorders: convulsion, dyskinesia, lethargy, somnolence, serotonin syndrome in combination with serotonergic drugs, and extrapyramidal disorder, motor and verbal tics.

Psychiatric Disorders: depression, hallucination, nervousness, and libido changes. Skin and Subcutaneous Tissue Disorders: alopecia.

Adverse Reactions with Oral Methylphenidate Products:

Nervousness and insomnia are the most common adverse reactions reported with other methylphenidate products. In children, loss of appetite, abdominal pain, weight loss during prolonged therapy, insomnia, and tachycardia may occur more frequently; however, any of the other adverse reactions listed below may also occur.

Other reactions include:

Cardiac Disorders: angina, arrhythmia, and pulse increased or decreased. Immune System Disorders: hypersensitivity reactions including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura.

Metabolism and Nutrition Disorders: anorexia and weight loss during prolonged therapy. Nervous System Disorders: drowsiness, rare reports of Tourette’s syndrome and toxic psychosis. Very rare reports of neuroleptic malignant syndrome (NMS) have been received, and, in most of these, patients were concurrently receiving therapies associated with NMS.

In a single report, a ten-year-old boy who had been taking methylphenidate for approximately 18 months experienced an NMS-like event within 45 minutes of ingesting his first dose of venlafaxine. It is uncertain whether this case represented a drug-drug interaction, a response to either drug alone, or some other cause.

Vascular Disorders: blood pressure increased or decreased and cerebral arteritis and/or occlusion. Although a definite causal relationship has not been established, the following have been reported in patients taking methylphenidate: Blood and Lymphatic System Disorders: leukopenia and/or anemia.

Hepatobiliary Disorders: abnormal liver function, ranging from transaminase elevation to severe hepatic injury. Psychiatric Disorders: transient depressed mood. Skin and Subcutaneous Tissue Disorders: scalp hair loss. Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis.

Erythema is commonly seen with use of methylphenidate transdermal system and is not by itself an indication of sensitization. However, contact sensitization should be suspected if erythema is accompanied by evidence of a more intense local reaction (edema, papules, vesicles) that does not significantly improve within 48 hours or spreads beyond the transdermal system site.

10 ) • External Heat: Patients should be advised to avoid exposing the methylphenidate transdermal system application site to direct external heat sources. When heat is applied to methylphenidate transdermal system after application, both the rate and extent of absorption are significantly increased.

11 ) • Hematologic monitoring: Periodic CBC, differential, and platelet counts are advised during prolonged therapy. , patients with significant hyperopia) should be evaluated by an ophthalmologist. 13 ) • Increased Intraocular Pressure (IOP) and Glaucoma: Prescribe methylphenidate transdermal system 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. 14 ) • Motor and Verbal Tics and Worsening of Tourette’s Syndrome: Before initiating methylphenidate transdermal system, 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. 1 Abuse, Misuse, and Addiction Methylphenidate transdermal system has a high potential for abuse and misuse.

The use of methylphenidate transdermal system exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. 2) ] . Misuse and abuse of CNS stimulants, including methylphenidate transdermal system, 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 methylphenidate transdermal system, assess each patient’s risk for abuse, misuse, and addiction. Educate patients and their caregivers or families about these risks. Advise patients to store methylphenidate transdermal system in a safe place, preferably locked, and instruct patients to not give methylphenidate transdermal system to anyone else.

Throughout methylphenidate transdermal system treatment, reassess each patient’s risk of abuse, misuse, and addiction and frequently monitor for signs and symptoms of abuse, misuse, and addiction. Methylphenidate transdermal system has special disposal instructions.

Instruct patients to find a take back location to dispose of unused or expired methylphenidate transdermal system. If a take back program is unavailable, instruct them to: 1. Remove methylphenidate transdermal system from its pouch, separate it from its liner, fold it in half with the adhesive sides touching each other, and immediately flush the used transdermal system down the toilet, and 2.

Place the pouch and liner in a container, close the container, and throw out the container in the trash (advise patients not to flush the pouch and liner down the toilet). 2 Risks to Patients with Serious Cardiac Disease Sudden death has been reported in patients with structural cardiac abnormalities or other serious cardiac disease who were treated with CNS stimulants at the recommended ADHD dosage.

Avoid methylphenidate transdermal system use in patients with known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmia, coronary artery disease, or other serious cardiac disease. 3 Increased Blood Pressure and Heart Rate CNS stimulants may cause an increase in blood pressure (mean increase approximately 2 to 4 mmHg) and heart rate (mean increase approximately 3 to 6 bpm).

Some patients may have larger increases. Monitor all methylphenidate transdermal system-treated patients for hypertension and tachycardia. 4 Psychiatric 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 Disease CNS stimulants may induce a manic or mixed episode in patients. , comorbid or history of depressive symptoms or a family history of suicide, bipolar disorder, or depression).

, hallucinations, delusional thinking, or mania) in patients without a prior history of psychotic illness or mania. 1% of CNS stimulant-treated patients compared with 0% of placebo-treated patients. If such symptoms occur, consider discontinuing methylphenidate transdermal system.

5 Seizures There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures.

In the presence of seizures, the drug should be discontinued. 6 Priapism Prolonged and painful erections, sometimes requiring surgical intervention, have been reported with methylphenidate use in both adult and pediatric male patients.

Although priapism was not reported with methylphenidate initiation, it developed after some time on the methylphenidate, often subsequent to an increase in dosage. Priapism also occurred during methylphenidate withdrawal (drug holidays or during discontinuation).

Methylphenidate transdermal system-treated patients who develop abnormally sustained or frequent and painful erections should seek immediate medical attention. 7 Peripheral Vasculopathy, including Raynaud’s phenomenon Stimulant medications, including methylphenidate transdermal system, 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 therapeutic dosages of CNS stimulants in all age groups throughout the course of treatment.

Signs and symptoms generally improved after dosage reduction or discontinuation of the CNS stimulant. Careful observation for digital changes is necessary during methylphenidate transdermal system treatment. , rheumatology referral) may be appropriate for methylphenidate transdermal system-treated patients who develop signs or symptoms of peripheral vasculopathy.

4) ] . CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. 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 methylphenidate transdermal system-treated pediatric patients.

Pediatric patients not growing or gaining height or weight as expected may need to have their treatment interrupted. 9 Chemical Leukoderma Methylphenidate transdermal system use may result in a persistent loss of skin pigmentation at and around the application site.

Loss of pigmentation, in some cases, has been reported at other sites distant from the application site. Chemical leukoderma can mimic the appearance of vitiligo, particularly when the loss of skin pigmentation involves areas distant from the application site.

Individuals with a history of vitiligo and/or a family history of vitiligo may be more at risk. Skin depigmentation may persist even after methylphenidate transdermal system use is discontinued. Monitor for signs of skin depigmentation, and advise patients to immediately inform their healthcare provider if changes in skin pigmentation occur.

Discontinue use of the methylphenidate transdermal system in patients with chemical leukoderma. 3%) was confirmed by transdermal system testing to be sensitized to methylphenidate (allergic contact dermatitis). This subject experienced erythema and edema at methylphenidate transdermal system application sites with concurrent urticarial lesions on the abdomen and legs resulting in treatment discontinuation.

This subject was not transitioned to oral methylphenidate. Use of methylphenidate transdermal system may lead to contact sensitization. Methylphenidate transdermal system should be discontinued if contact sensitization is suspected. Erythema is commonly seen with use of methylphenidate transdermal system and is not by itself an indication of sensitization.

However, contact sensitization should be suspected if erythema is accompanied by evidence of a more intense local reaction (edema, papules, vesicles) that does not significantly improve within 48 hours or spreads beyond the transdermal system site.

Confirmation of a diagnosis of contact sensitization (allergic contact dermatitis) may require further diagnostic testing. , orally. Manifestations of systemic sensitization may include a flare-up of previous dermatitis or of prior positive transdermal system-test sites, or generalized skin eruptions in previously unaffected skin.

Other systemic reactions may include headache, fever, malaise, arthralgia, diarrhea, or vomiting. No cases of systemic sensitization have been observed in clinical trials of methylphenidate transdermal system. Patients who develop contact sensitization to methylphenidate transdermal system and require oral treatment with methylphenidate should be initiated on oral medication under close medical supervision.

It is possible that some patients sensitized to methylphenidate by exposure to methylphenidate transdermal system may not be able to take methylphenidate in any form. , while wearing the transdermal system. When heat is applied to methylphenidate transdermal system after application, both the rate and extent of absorption are significantly increased.

3) ] . This increased absorption can be clinically significant and can result in overdose of methylphenidate [see Overdosage (10) ] . 12 Hematologic Monitoring Periodic CBC, differential, and platelet counts are advised during prolonged therapy.

13 Acute Angle Closure Glaucoma There have been reports of angle closure glaucoma associated with methylphenidate treatment. , patients with significant hyperopia) should be evaluated by an ophthalmologist. 2) ] . Prescribe methylphenidate transdermal system to patients with open-angle glaucoma or abnormally increased IOP only if the benefit of treatment is considered to outweigh the risk.

Closely monitor methylphenidate transdermal system -treated patients with a history of abnormally increased IOP or open angle glaucoma. 15 Motor and Verbal Tics, and Worsening of Tourette’s Syndrome CNS stimulants, including methylphenidate, have been associated with the onset or exacerbation of motor and verbal tics.

2) ] . Before initiating methylphenidate transdermal system, assess the family history and clinically evaluate patients for tics or Tourette’s syndrome. Regularly monitor methylphenidate transdermal system -treated patients for the emergence or worsening of tics or Tourette’s syndrome, and discontinue treatment if clinically appropriate.