Addwize

Addwize is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD).

The efficacy of Addwize in the treatment of ADHD was established in 2 controlled trials of patients aged 6 to 17 years of age who met DSM-IV criteria for ADHD.

A diagnosis of ADHD (DSM-IV) implies the presence of hyperactive-impulsive or inattentive symptoms that cause impairment and were present before age 7 years. The symptoms must cause clinically significant impairment, e.g., in social, academic, or occupational functioning; and be present in 2 or more settings, e.g., school (or work) and at home. The symptoms must not be better accounted for by another mental disorder. For the inattentive type, at least 6 of the following symptoms must have persisted for at least 6 months: lack of attention to details/careless mistakes; lack of sustained attention; poor listener; failure to follow through on tasks; poor organization; avoids tasks requiring sustained mental effort; loses things; easily distracted; forgetful. For the Hyperactive-Impulsive Type, at least 6 of the following symptoms must have persisted for at least 6 months: fidgeting/squirming; leaving seat; inappropriate running/climbing; difficulty with quiet activities; “on the go,” excessive talking; blurting answers; can't wait turn; intrusive. The Combined Type requires both inattentive and hyperactive-impulsive criteria to be met.

Special Diagnostic Considerations

Specific etiology of this syndrome is unknown, and there is no single diagnostic test. Adequate diagnosis requires the use not only of medical but of special psychological, educational, and social resources. Learning may or may not be impaired. The diagnosis must be based upon a complete history and evaluation of the child and not solely on the presence of the required number of DSM-IV characteristics.

Need For Comprehensive Treatment Program

Addwize is indicated as an integral part of a total treatment program for ADHD that may include other measures (psychological, educational, social) for patients with this syndrome. Drug treatment may not be indicated for all patients with this syndrome. Stimulants are not intended for use in the patient who exhibits symptoms secondary to environmental factors and/or other primary psychiatric disorders, including psychosis. Appropriate educational placement is essential and psychosocial intervention is often helpful. When remedial measures alone are insufficient, the decision to prescribe stimulant medication will depend upon the physician's assessment of the chronicity and severity of the patient's symptoms.

Long-term Use

The effectiveness of Addwize for long-term use, i.e., for more than 6 weeks, has not been systematically evaluated in controlled trials. Therefore, the physician who elects to use Addwize for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.

Addwize is used to treat attention deficit hyperactivity disorder (ADHD). It belongs to the group of medicines called central nervous system (CNS) stimulants.

Addwize increases attention and decreases restlessness in patients who are hyperactive, cannot concentrate, or are easily distracted. It is used as part of a total treatment program that also includes social, educational, and psychological therapy.

Addwize is available only with a doctor's prescription. Prescriptions cannot be refilled. A new prescription must be obtained from your doctor each time you need Addwize.

Addwize is for oral administration once daily in the morning.

Addwize may be swallowed as whole capsules or alternatively may be administered by sprinkling the capsule contents on a small amount of applesauce. Addwize capsules and/or their contents should not be crushed, chewed, or divided.

The capsules may be carefully opened and the beads sprinkled over a spoonful of applesauce. The mixture of drug and applesauce should be consumed immediately in its entirety. The drug and applesauce mixture should not be stored for future use.

Dosage should be individualized according to the needs and responses of the patient.

Patients New to Addwize

The recommended starting dose of Addwize for patients who are not currently taking Addwize or racemic Addwize, or for patients who are on stimulants other than Addwize, is 5 mg/day for pediatric patients and 10 mg/day for adult patients.

Dosage may be adjusted in 5 mg increments for pediatric patients and in 10 mg increments for adult patients. In general, dosage adjustments may proceed at approximately weekly intervals. The patient should be observed for a sufficient duration at a given dose to ensure that a maximal benefit has been achieved before a dose increase is considered. In dose-response (fixed-dose) studies (pediatric from 10 to 30 mg/day and adult from 20 to 40 mg/day), all doses were effective vs. placebo. There was no clear finding, however, of greater average benefits for the higher doses compared to the lower doses. Adverse events and discontinuations, however, were dose-related. Doses above 30 mg/day in pediatrics and 40 mg/day in adults have not been studied and are not recommended.

Patients Currently Using Addwize

For patients currently using Addwize, the recommended starting dose of Addwize is half the total daily dose of racemic Addwize. Patients currently using Addwize (Addwize) may be switched to the same daily dose of Addwize.

Maintenance/Extended Treatment

There is no body of evidence available from controlled trials to indicate how long the patient with ADHD should be treated with Addwize. It is generally agreed, however, that pharmacological treatment of ADHD may be needed for extended periods. Nevertheless, the physician who elects to use Addwize for extended periods in patients with ADHD should periodically reevaluate the long-term usefulness of the drug for the individual patient with periods off medication to assess the patient’s functioning without pharmacotherapy. Improvement may be sustained when the drug is either temporarily or permanently discontinued.

Dose Reduction and Discontinuation

If paradoxical aggravation of symptoms or other adverse events occur, the dosage should be reduced, or, if necessary, the drug should be discontinued.

If improvement is not observed after appropriate dosage adjustment over a 1-month period, the drug should be discontinued.

See also:
What is the most important information I should know about Addwize?

Do not use Addwize if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Before using this medication, tell your doctor if you have severe depression, seizures or epilepsy, high blood pressure, heart disease, a heart rhythm disorder, congestive heart failure, if you have recently had a heart attack, or if you have a history of mental illness or drug/alcohol addiction.

Some stimulants have caused sudden death in children and adolescents with serious heart problems or congenital heart defects. Before taking Addwize, tell your doctor if you have any type of heart problems.

Long-term use of Addwize can slow a child's growth. Tell your doctor if the child using this medication is not growing or gaining weight properly.

Addwize may be habit-forming and should be used only by the person for whom it was prescribed. Keep the medication in a secure place where others cannot get to it.

Keep track of the amount of medicine used from each new bottle. Addwize is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

Use Addwize extended-release capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Addwize extended-release capsules comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Addwize extended-release capsules refilled.
• Take Addwize extended-release capsules by mouth in the morning. Talk with your doctor about how you should take Addwize extended-release capsules with regard to food.
• Swallow Addwize extended-release capsules whole. Do not break, crush, or chew before swallowing.
• If you cannot swallow the capsule whole, you may open it and sprinkle the contents over a spoonful of applesauce. Swallow the mixture right away, followed by a glass of water. Do not crush or chew the medicine before swallowing. Do not store the mixture for future use.
• If you take an antacid, H antagonist (eg, ranitidine), or proton pump inhibitor (eg, omeprazole), ask your doctor or pharmacist how to take it with Addwize extended-release capsules.
• If you miss a dose of Addwize extended-release capsules, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Addwize extended-release capsules.

Use: Labeled Indications

ADHD: Treatment of ADHD

See also:
What other drugs will affect Addwize?

Acebrophylline: May enhance the stimulatory effect of CNS Stimulants. Avoid combination

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Monitor therapy

Antacids: May increase the absorption of Addwize. Specifically, antacids may interfere with the normal release of drug from the extended-release capsules (Addwize brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Antihypertensive Agents: Addwize may diminish the therapeutic effect of Antihypertensive Agents. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Esketamine: May enhance the hypertensive effect of CNS Stimulants. Monitor therapy

Fosphenytoin: Addwize may increase the serum concentration of Fosphenytoin. Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Histamine H2 Receptor Antagonists: May increase the absorption of Addwize. Specifically, H2-antagonists may interfere with the normal release of drug from the extended-release capsules (Addwize brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Inhalational Anesthetics: Addwize may enhance the hypertensive effect of Inhalational Anesthetics. Avoid combination

Iobenguane Radiopharmaceutical Products: CNS Stimulants may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Avoid combination

Ioflupane I 123: Addwize may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of Addwize. Avoid combination

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Management: Concomitant use of ozanimod with sympathomimetic agents is not recommended. If combined, monitor patients closely for the development of hypertension, including hypertensive crises. Consider therapy modification

PHENobarbital: Addwize may increase the serum concentration of PHENobarbital. Monitor therapy

Phenytoin: Addwize may increase the serum concentration of Phenytoin. Monitor therapy

Primidone: Addwize may increase serum concentrations of the active metabolite(s) of Primidone. Specifically, phenobarbital concentrations could become elevated. Addwize may increase the serum concentration of Primidone. Monitor therapy

Proton Pump Inhibitors: May increase the absorption of Addwize. Specifically, proton pump inhibitors may interfere with the normal release of drug from the extended-release capsules (Addwize brand), which could result in both increased absorption (early) and decreased delayed absorption. Monitor therapy

Serotonergic Agents (High Risk): Addwize-Addwize may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Exceptions: Isocarboxazid; Linezolid; Methylene Blue; Moclobemide; Phenelzine; Tranylcypromine. Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Monitor therapy

Solriamfetol: CNS Stimulants may enhance the hypertensive effect of Solriamfetol. CNS Stimulants may enhance the tachycardic effect of Solriamfetol. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Addwize may increase the serum concentration of Vitamin K Antagonists. Monitor therapy

See also:
What are the possible side effects of Addwize?

Addwize was administered to 46 children and 7 adolescents with ADHD for up to 7 weeks and 206 adults with ADHD in clinical studies. During the clinical studies, 101 adult patients were treated for at least 6 months.

Adverse events during exposure were obtained primarily by general inquiry and recorded by 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 events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and listings that follow, MedDRA terminology has been used to classify reported adverse events. The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Adverse Events Associated with Discontinuation of Treatment in Acute Clinical Studies with Addwize-Children

Overall, 50 of 684 children treated with Addwize immediate-release formulation (7.3%) experienced an adverse event that resulted in discontinuation. The most common reasons for discontinuation were twitching (described as motor or vocal tics), anorexia, insomnia, and tachycardia (approximately 1% each). None of the 53 Addwize-treated pediatric patients discontinued treatment due to adverse events in the 7-week, placebo-controlled study.

Adverse Events Occurring at an Incidence of 5% or More Among Addwize-Treated Patients-Children

Table 1 enumerates treatment-emergent adverse events for the placebo-controlled, parallel-group study in children and adolescents with ADHD at flexible Addwize doses of 5-30 mg/day. The table includes only those events that occurred in 5% or more of patients treated with Addwize and for which the incidence in patients treated with Addwize was at least twice the incidence in placebo-treated patients. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse event incidence rate in the population studied.

1Events, regardless of causality, for which the incidence for patients treated with Addwize was at least 5% and twice the incidence among placebo-treated patients. Incidence has been rounded to the nearest whole number.

Table 2 below enumerates the incidence of dose-related adverse events that occurred during a fixed-dose, double-blind, placebo-controlled trial of Addwize up to 30mg/day versus placebo in children and adolescents with ADHD.

Adverse Events Associated with Discontinuation of Treatment in Clinical Studies with Addwize-Adults

In the adult placebo-controlled study, 10.7% of the Addwize-treated patients and 7.5% of the placebo-treated patients discontinued for adverse events. Among Addwize-treated patients, insomnia (1.8%, n=3), feeling jittery (1.8%, n=3), anorexia (1.2%, n=2), and anxiety (1.2%, n=2) were the reasons for discontinuation reported by more than 1 patient.

Adverse Events Occurring at an Incidence of 5% or More Among Addwize-Treated Patients-Adults

Table 3 enumerates treatment-emergent adverse events for the placebo-controlled, parallel-group study in adults with ADHD at fixed Addwize doses of 20, 30, and 40 mg/day. The table includes only those events that occurred in 5% or more of patients in a Addwize dose group and for which the incidences in patients treated with Addwize appeared to increase with dose. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.

1Events, regardless of causality, for which the incidence was at least 5% in a Addwize group and which appeared to increase with randomized dose. Incidence has been rounded to the nearest whole number.

Two other adverse reactions occurring in clinical trials with Addwize at a frequency greater than placebo, but which were not dose related were: feeling jittery (12% and 2%, respectively) and dizziness (6% and 2%, respectively).

Table 4 summarizes changes in vital signs and weight that were recorded in the adult study (N=218) of Addwize in the treatment of ADHD.

Postmarketing Experience

The following additional adverse reactions have been identified during postapproval use of Addwize. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency:

Musculoskeletal: rhabdomyolysis

Immune System Disorders: hypersensitivity reactions, including angioedema and anaphylaxis

Adverse Events with Other Addwize HCl Dosage Forms

Nervousness and insomnia are the most common adverse reactions reported with other Addwize 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: angina, arrhythmia, palpitations, pulse increased or decreased, tachycardia

Gastrointestinal: abdominal pain, nausea

Immune: hypersensitivity reactions including skin rash, urticaria, fever, arthralgia, exfoliative dermatitis, erythema multiforme with histopathological findings of necrotizing vasculitis, and thrombocytopenic purpura

Metabolism/Nutrition: anorexia, weight loss during prolonged therapy

Nervous System: dizziness, drowsiness, dyskinesia, headache, rare reports of Tourette’s syndrome, toxic psychosis

Vascular: blood pressure increased or decreased, cerebral arteritis and/or occlusion

Although a definite causal relationship has not been established, the following have been reported in patients taking Addwize:

Blood/Lymphatic: leukopenia and/or anemia

Hepatobiliary: abnormal liver function, ranging from transaminase elevation to hepatic coma

Psychiatric: transient depressed mood, aggressive behavior, libido changes

Skin/Subcutaneous: scalp hair loss

Urogenital: priapism

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 10-year-old boy who had been taking Addwize 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.

Addwize is the dextrorotary form of Addwize. It is a norepinephrine-dopamine reuptake inhibitor (NDRI) and thus a psychostimulant. It is used for treatment of Attention Deficit Hyperactivity Disorder (ADHD).