Adhansia XR (methylphenidate HCI)

WARNING

ABUSE AND DEPENDENCE

CNS stimulants, including Adhansia XR , 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.

Adhansia XR may cause serious side effects including:

• hives,
• difficulty breathing,
• swelling of your face, lips, tongue, or throat,
• chest pain,
• trouble breathing,
• lightheadedness,
• hallucinations,
• new behavior problems,
• aggression,
• hostility,
• paranoia,
• numbness,
• pain,
• cold feeling,
• unexplained wounds,
• skin color changes (pale, red, or blue appearance) in your fingers or toes, and
• penis erection that is painful or last 4 hours or longer

Get medical help right away, if you have any of the symptoms listed above.

The most common side effects of Adhansia XR include:

• excessive swelling,
• mood changes,
• nervousness,
• irritableness,
• sleep problems (insomnia),
• fast heart rate,
• pounding heartbeats,
• fluttering in your chest,
• increased blood pressure,
• loss of appetite,
• weight loss,
• dry mouth,
• nausea,
• stomach pain, and
• headache

Tell the doctor if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Adhansia XR. For more information, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Drug Abuse And Dependence

Controlled Substance

Adhansia XR contains methylphenidate, a Schedule II controlled substance.

Abuse

• CNS stimulants including Adhansia XR, other methylphenidate-containing products, and amphetamines have a high potential for abuse. Abuse is the intentional non-therapeutic use of a drug, even once, to achieve a desired psychological or physiological effect. 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 Adhansia XR, 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 Adhansia XR use.

Dependence

Tolerance

• 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) may occur during chronic therapy with CNS stimulants including Adhansia XR.

Dependence

• 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 Adhansia XR.
• 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.

Pretreatment Screening

• Prior to initiating treatment with Adhansia XR, 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 Adhansia XR use.

General Dosing Information

• Administer Adhansia XR orally once daily in the morning with or without food.
• The recommended starting dose of Adhansia XR for patients 6 years or older is 25 mg once daily. Titrate the dose in increments of 10 to 15 mg at intervals of no less than 5 days.
• Dosages higher than 100 mg daily in adults and 85 mg daily in pediatric patients have not been evaluated in clinical trials and are not recommended. Although efficacy was demonstrated in short-term controlled trials in adults at dosages of 100 mg daily, dosages above 85 mg daily were associated with a disproportionate increase in the incidence of certain adverse reactions.
• In short-term controlled trials in pediatric patients, efficacy was demonstrated at dosages of 70 mg daily, but dosages 70 mg daily and higher were associated with a disproportionate increase in the incidence of certain adverse reactions. Individualize dosage adjustments based upon assessment of clinical benefit and tolerability with careful consideration of the dose-related adverse reactions.
• Adhansia XR may be taken whole or the capsule may be opened and the entire contents sprinkled onto a tablespoon of applesauce or yogurt. The entire mixture should be consumed immediately or within 10 minutes.
• If the mixture is not consumed within 10 minutes after mixing, it should be discarded and not stored. Patients should take the entire contents of the capsule sprinkled on the chosen food in its entirety, without chewing. The dose of a single capsule should not be divided. Patients should not take anything less than one capsule per day.
• In the event of a missed dose, do not administer later in the day. Do not administer additional medication to make up for the missed dose.
• Pharmacological treatment of ADHD may be needed for extended periods. Periodically re-evaluate the long-term use of Adhansia XR, and adjust dosage as needed.

Dose Reduction And Discontinuation

• If paradoxical aggravation of symptoms or other adverse reactions occur, reduce the dosage, or, if necessary, discontinue the drug. Adhansia XR should be periodically discontinued to assess the patient's condition. If improvement is not observed after appropriate dosage adjustment over a one-month period, discontinue Adhansia XR.

Switching From Other Methylphenidate Products

• If switching from other methylphenidate products, discontinue that treatment, and titrate with Adhansia XR using the titration schedule above.
• Do not substitute Adhansia XR for other methylphenidate products on a milligram-per-milligram basis because of different methylphenidate base compositions and differing pharmacokinetic profiles.

Clinically Important Drug Interactions

Table 3 presents clinically important drug interactions with Adhansia XR.

Table 3: Drugs Having Clinically Important Interactions with Adhansia XR

• 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. 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 Adhansia XR and any potential adverse effects on the breastfed infant from Adhansia XR or from the underlying maternal condition.