DAYTRANA® (methylphenidate transdermal system), CII

DAYTRANA® (methylphenidate transdermal system), CII

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DAYTRANA® (methylphenidate transdermal system), CII

DAYTRANA is an adhesive-based matrix transdermal system (patch) containing methylphenidate that is applied to intact skin. The chemical name for methylphenidate is α-phenyl-2-piperidineacetic acid methyl ester. It is a white to off-white powder and is soluble in alcohol, ethyl acetate, and ether. Methylphenidate is practically insoluble in water and petrol ether. Its molecular weight is 233.31. Its empirical formula is C14H19NO2.

Patch Components

DAYTRANA contains methylphenidate in a multipolymeric adhesive. The methylphenidate is dispersed in acrylic adhesive that is dispersed in a silicone adhesive. The composition per unit area of all dosage strengths is identical, and the total dose delivered is dependent on the patch size and wear time.

The active component of the patch is methylphenidate. The remaining components are pharmacologically inactive.

Indications and usage

  • DAYTRANA is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).
  • Children (ages 6-12): the efficacy of DAYTRANA in ADHD was established in two 7-week controlled trials in children
  • Adolescents (ages 13-17): the efficacy of DAYTRANA in ADHD was established in one 7-week, controlled study in adolescents

Mechanism of Action

Methylphenidate is a central nervous system (CNS) stimulant. Its mode of therapeutic action in Attention Deficit Hyperactivity Disorder (ADHD) is not known.

Dosage and administration

It is recommended that DAYTRANA be applied to the hip area 2 hours before an effect is needed and should be removed 9 hours after application. Dosage should be titrated to effect. Dose titration, final dosage, and wear time should be individualized according to the needs and response of the patient.


Week 1Week 2Week 3Week 4
Patch Size12.5 cm218.75 cm225 cm237.5 cm2
Nominal Delivered Dose* (mg/9 hours)10mg15mg20mg30mg
Delivery Rate*(1.1 mg/hr)*(1.6 mg/hr)*(2.2 mg/hr)*(3.3 mg/hr)*

*Nominal in vivo delivery rate in children and adolescents when applied to the hip, based on a 9-hour wear period.

Contraindications

Hypersensitivity to Methylphenidate: DAYTRANA is contraindicated in patients known to be hypersensitive to methylphenidate or other components of the product (polyester/ethylene vinyl acetate laminate film backing, acrylic adhesive, silicone adhesive, and fluoropolymer-coated polyester).

Agitation: DAYTRANA is contraindicated in patients with marked anxiety, tension, and agitation, since the drug may aggravate these symptoms.

Glaucoma: DAYTRANA is contraindicated in patients with glaucoma.

Tics: DAYTRANA is contraindicated in patients with motor tics or with a family history or diagnosis of Tourette’s syndrome.

Monoamine Oxidase Inhibitors: DAYTRANA is contraindicated during treatment with monoamine oxidase inhibitors, and also within a minimum of 14 days following discontinuation of treatment with a monoamine oxidase inhibitor (hypertensive crises may result).

Warnings and precautions

  • Serious Cardiovascular Events: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Sudden death, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Stimulant products generally should not be used in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious heart problems.
  • Increase in Blood Pressure: Monitor patients for changes in heart rate and blood pressure and use with caution in patients for whom an increase in blood pressure or heart rate would be problematic.
  • Psychiatric Adverse Events: Use of stimulants may cause treatmentemergent psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychiatric illness. Clinical evaluation for Bipolar Disorder is recommended prior to stimulant use. Monitor for aggressive behavior.
  • Seizures: Stimulants may lower the convulsive threshold. Discontinue in the presence of seizures.
  • Priapism: Cases of painful and prolonged penile erections and priapism have been reported with methylphenidate products. Immediate medical attention should be sought if signs or symptoms of prolonged penile erections or priapism are observed
  • Peripheral Vasculopathy, including Raynaud’s phenomenon: Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants.
  • Long-Term Suppression of Growth: Monitor height and weight at appropriate intervals in pediatric patients.
  • Chemical Leukoderma: DAYTRANA 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. Monitor for signs of skin depigmentation. Discontinue DAYTRANA if it occurs.
  • Contact Sensitization: Use of DAYTRANA may lead to contact sensitization. Treatment should be discontinued if contact sensitization is suspected. Erythema is commonly seen with use of DAYTRANA 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 patch site.
  • Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.
  • External Heat: Patients should be advised to avoid exposing the DAYTRANA application site to direct external heat sources. When heat is applied to DAYTRANA after patch application, both the rate and extent of absorption are significantly increased.
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  • Hematologic monitoring: Periodic CBC, differential, and platelet counts are advised during prolonged therapy.

Adverse reactions

  • Children (ages 6-12): The most commonly (≥5% and twice the rate of placebo) reported adverse reactions in a placebo-controlled trial in children aged 6-12 included appetite decreased, insomnia, nausea, vomiting, weight decreased, tic, affect lability, and anorexia .
  • Adolescents (ages 13-17): The most commonly (≥5% and twice the rate of placebo) reported adverse reactions in a placebo-controlled trial in adolescents aged 13-17 included appetite decreased, nausea, insomnia, weight decreased, dizziness, abdominal pain, and anorexia. The majority of subjects in these trials had erythema at the application site.
  • The most common (≥2% of subjects) adverse reaction associated with discontinuations in controlled clinical trials in children or adolescents was application site reactions

Drug interactions

Monoamine Oxidase Inhibitors (MAOI): Concomitant use of MAOIs and CNS stimulants, including DAYTRANA, can cause hypertensive crisis. Potential outcomes include death, stroke, myocardial infarction, aortic dissection, ophthalmological complications, eclampsia, pulmonary edema, and renal failure. Concomitant use of DAYTRANA with MAOIs or within 14 days after discontinuing MAOI treatment is contraindicated.

Vasopressor Agents: Because of a possible effect on blood pressure, DAYTRANA should be used cautiously with pressor agents

Antihypertensive Drugs: DAYTRANA may decrease the effectiveness of drugs used to treat hypertension. Monitor blood pressure and adjust the dosage of the antihypertensive drug as needed.

Coumarin Anticoagulants, Antidepressants, and Selective Serotonin Reuptake Inhibitors: Human pharmacologic studies have shown that methylphenidate may inhibit the metabolism of coumarin anticoagulants, anticonvulsants (e.g., phenobarbital, phenytoin, primidone), and some tricyclic drugs (e.g., imipramine, clomipramine, desipramine) and selective serotonin reuptake inhibitors. Downward dose adjustments of these drugs may be required when given concomitantly with methylphenidate. It may be necessary to adjust the dosage and monitor plasma drug concentrations (or, in the case of coumarin, coagulation times), when initiating or discontinuing methylphenidate.

Risperidone: Combined use of methylphenidate with risperidone when there is a change in dosage, whether an increase or decrease, of either or both medications, may increase the risk of extrapyramidal symptoms (EPS). Monitor for signs of EPS.

Use in specific populations

Pregnancy: Published studies and post-marketing reports on methylphenidate use during pregnancy are insufficient to identify 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.

CNS stimulants, such as DAYTRANA, 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.

Lactation: Limited published literature, based on breast milk sampling from five mothers, reports that 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 DAYTRANA and any potential adverse effects on the breastfed infant from DAYTRANA or from the underlying maternal condition.

Pediatric Use: DAYTRANA should not be used in children under six years of age, since safety and efficacy in this age group have not been established. Long-term effects of methylphenidate in children have not been well established.

Drug abuse and dependence

Controlled Substance: DAYTRANA is classified as a Schedule II controlled substance by federal regulation.

Overdosage

Signs and symptoms of acute methylphenidate overdosage, resulting principally from overstimulation of the CNS and from excessive sympathomimetic effects, may include the following: vomiting, agitation, tremors, hyperreflexia, muscle twitching, convulsions (may be followed by coma), euphoria, confusion, hallucinations, delirium, sweating, flushing, headache, hyperpyrexia, tachycardia, palpitations, cardiac arrhythmias, hypertension, mydriasis, dryness of mucous membranes, and rhabdomyolysis.

Recommended Treatment

Remove all patches immediately and cleanse the area(s) to remove any remaining adhesive. The continuing absorption of methylphenidate from the skin, even after removal of the patch, should be considered when treating patients with overdose. Treatment consists of appropriate supportive measures. The patient must be protected against self-injury and against external stimuli that would aggravate overstimulation already present. Intensive care must be provided to maintain adequate circulation and respiratory exchange; external cooling procedures may be required for hyperpyrexia.

Efficacy of peritoneal dialysis or extracorporeal hemodialysis for DAYTRANA overdosage has not been established.

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