Adverse Reactions

Table: Adverse reactions reported by 5% or more of adults (ages 18 to 55 years) taking Mydayis and that were at least twice the incidence in patients taking placebo in the 4-, 6-, and 7-week clinical trials.¹

The most common adverse reactions (incidence ≥5% and at a rate at least twice placebo) in pediatric patients (13 to 17 years) with ADHD were decreased appetite (22% Mydayis n=78, 6% placebo n=79), insomnia (8%, 3%), nausea (8%, 4%), irritability (6%, 3%), and decreased weight (5%, 1%).

Safety data in adults are pooled from 3 controlled trials including dose-optimization and forced-dose titration studies with 626 adult patients exposed to Mydayis doses of 12.5 mg to 75 mg per day. Includes doses up to 75 mg (1.5 times the maximum adult dosage).

Discontinuation rates¹

In the controlled trials of adult patients aged 18 to 55 years, 9% of Mydayis-treated patients discontinued due to adverse reactions, compared to 2% of placebo-treated patients. The most frequent adverse reactions leading to discontinuation of adult patients (i.e., leading to discontinuation in at least 1% of Mydayis-treated patients and at a rate at least twice that of placebo) were insomnia (2%), increased blood pressure (2%), decreased appetite (1%), and headache (1%).

In a controlled trial including adolescent patients (ages 13 to 17 years), 5% (4/78) of Mydayis-treated patients discontinued due to adverse reactions compared to 0% (0/79) of placebo-treated patients. The most frequent adverse reaction leading to discontinuation (i.e. leading to discontinuation in at least 1% of Mydayis-treated patients and at a rate at least twice that of placebo) were dizziness (1%, n=1), depression (1%, n=1), and abdominal pain upper (1%, n=1), and viral infection (1%, n=1).

Long-term Safety Study²

Long-term safety of Mydayis was studied in a 12-month open-label safety study in 505 adults aged 18 to 55 years who had completed 4 weeks or more of treatment in dose-optimization Study 301 or forced-dose titration Study 303. The tolerability and safety profile of Mydayis over this 12-month treatment period was comparable to that seen in short-term studies. Pharmacological treatment of ADHD may be needed for an extended period. Periodically re-evaluate the long-term use of Mydayis and adjust dosage as needed.

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 and their caregivers that Mydayis is a federally controlled substance because it can be abused or lead to dependence. Advise patients to store Mydayis 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 Mydayis by a medicine take-back program if available.

Serious Cardiovascular Risks

Advise patients, caregivers, and family members that there is a potential serious cardiovascular risk including sudden death, myocardial infarction, stroke, and hypertension, with Mydayis use. 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

Instruct patients that Mydayis can cause elevations of their blood pressure and pulse rate and they should be monitored for such effects.

Psychiatric Risks

Advise patients that Mydayis, at recommended doses, may cause psychotic or manic symptoms, even in patients without prior history of psychotic symptoms or mania.

Long-Term Suppression of Growth

Advise patients, family members, and caregivers that amphetamines may cause slowing of growth, including weight loss.

Circulation Problems in Fingers and Toes (Peripheral Vasculopathy, Including Raynaud’s Phenomenon)

Instruct patients beginning treatment with Mydayis 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 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 Mydayis. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Seizures

Caution patients that Mydayis may lower the convulsive threshold. Advise patients to contact their healthcare provider immediately and to discontinue Mydayis if a seizure occurs.

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome with concomitant use of Mydayis and other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular MAOIs, both those intended to treat psychiatric disorders and also others such as linezolid). Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome.

Concomitant Medications

Advise patients to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs because there is a potential for interactions.

Pregnancy

Advise patients of the potential fetal effects from the use of Mydayis during pregnancy. Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with Mydayis.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Mydayis during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/research/pregnancyregistry/.

Lactation

Advise women not to breastfeed if they are taking Mydayis.

Alcohol

Advise patients to avoid alcohol while taking Mydayis. Consumption of alcohol while taking Mydayis may result in a more rapid release of the dose of mixed amphetamine salts.

This patient counseling information does not include all the information needed to use Mydayis. See Full Prescribing Information.

References

Mydayis [package insert]. Lexington, MA; Takeda US Inc.
Adler LA, Frick G, Yan B. A long-term, open-label, safety study of triple-bead mixed amphetamine salts (SHP465) in adults with ADHD. J Atten Disord. 2017; doi:10.1177/1087054717696770.

Clinical Data

Dosing + Administration

INDICATION AND LIMITATIONS OF USE

MYDAYIS^® is indicated for the treatment of ADHD in patients ≥13 years. Patients ≤12 years experienced higher plasma exposure at the same dose and higher rates of adverse reactions, mainly insomnia and decreased appetite.

IMPORTANT SAFETY INFORMATION

WARNING: ABUSE AND DEPENDENCE

CNS stimulants, including Mydayis, other amphetamine-containing products, and methylphenidate, 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.

Contraindications
- Known hypersensitivity to amphetamines or other ingredients of Mydayis. Angioedema and anaphylactic reactions have been reported with other amphetamines.
- Use with monoamine oxidase inhibitors (MAOIs) or within 14 days of last MAOI dose, due to increased risk of hypertensive crisis.
Warnings and Precautions
- Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Sudden death, stroke and myocardial infarction have been reported in adults with CNS stimulants at recommended doses, as well as sudden death in pediatric patients with structural cardiac abnormalities and other serious heart problems while taking CNS stimulants at recommended doses. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Mydayis treatment.
- CNS stimulants cause increased blood pressure (mean increase ~2-4 mm Hg) and heart rate (mean increase ~3-6 bpm). Monitor for tachycardia and hypertension.
- Exacerbation of Pre-existing Psychosis : 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 : May induce a mixed/manic episode in patients with bipolar disorder. Prior to initiating treatment, screen for risk factors for developing a manic episode (e.g., comorbid or history of depressive symptoms, or a family history of suicide, bipolar disorder, and depression). New Psychotic or Manic Symptoms : At recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients with no prior history of psychotic illness or mania. Discontinue if symptoms occur.
- CNS stimulants are associated with weight loss and slowing of growth rate in pediatric patients (monitor weight and height). Treatment may need to be interrupted in patients not growing or gaining weight as expected. Mydayis is not approved in pediatric patients ≤12 years.
- CNS stimulants are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; very rare sequelae include digital ulceration and/or soft tissue breakdown. Careful observation for digital changes is necessary during treatment with ADHD stimulants; further evaluation and referral may be required.
- Mydayis may lower the convulsive threshold in patients with prior history of seizure, prior EEG abnormalities in the absence of seizures, and in patients without a history of seizures and no prior EEG evidence of seizures. Discontinue if a seizure occurs.
- Increased risk of serotonin syndrome when co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. Discontinue Mydayis if it occurs and initiate supportive treatment.
- To avoid substitution errors and overdosage, do not substitute for other amphetamines on a mg-per-mg basis because of different amphetamine base compositions and differing PK profiles.
Adverse Reactions
Most common adverse reactions in patients with ADHD (incidence ≥5% and at a rate at least twice placebo) are:
- Pediatrics (13 years and older) : insomnia, decreased appetite, decreased weight, irritability, and nausea.
- Adults : insomnia, decreased appetite, decreased weight, dry mouth, increased heart rate, and anxiety.
Pregnancy and Lactation
Mydayis may cause fetal harm. Breastfeeding is not recommended during Mydayis treatment.

Please click for Full Prescribing Information.

Takeda is committed to helping ensure the proper use of stimulant medication. Please see the Proper Use of Prescription Stimulant Medication for additional information.