Zenzedi

Mechanism of Action

Sympathomimetic amine that promotes release of dopamine and norepinephrine from their storage sites in the presynaptic nerve terminals; may also block reuptake of catecholamines by competitive inhibition.

Absorption

Peak plasma time: ~3 hr (immediate release); ~8 hr (sustained release)

Onset of action: 1-1.5 hr

Metabolism

Hepatic via glucuronidation and mono-oxygenase

Elimination

Half-life: 7-24 hr, dependent on urinary pH

Half-life elimination: 10-13 hr (adults)

Excretion: Urine

Zenzedi is part of the drug class:

• Centrally acting sympathomimetics

Take the missed dose as soon as you remember, but not late in the day. Skip the missed dose if it is almost evening. Do not take extra medicine to make up the missed dose.

It is very important that your doctor check you or your child's progress at regular visits to make sure that your dose is right and that the medicine is helping you. Your doctor will need to check your or your child's blood, heart, and blood pressure for any problems or unwanted effects that may be caused by this medicine.

You should not use this medicine if you or your child are using or have used an MAO inhibitor (MAOI) such as Eldepryl®, Marplan®, Nardil®, or Parnate® within the past 14 days.

This medicine may cause serious allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.

Tell your doctor about all the medicines you or your child take or plan to take, including prescription and nonprescription (over-the-counter) medicines, dietary supplements, herbal remedies, or medicines for appetite control, asthma, colds, cough, hay fever, and sinus problems.

This medicine may cause serious heart or blood vessel problems. This may be more likely in patients who have a family history of heart disease. Check with your doctor right away if you or your child have chest pain, trouble breathing, or fainting while taking this medicine.

This medicine may cause some people to feel a false sense of well-being or to become dizzy, lightheaded, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous until you know how this medicine affects you.

Check with your doctor immediately if blurred vision, difficulty in reading, or any other change in vision occurs during or after treatment. Your doctor may want you or your child to have your eyes checked by an ophthalmologist (eye doctor).

Tell your doctor right away if you or your family notices any unusual changes in behavior, such as an increase in aggression, hostility, agitation, irritability, or suicidal thinking or behaviors. Also tell your doctor if you or your child have hallucinations or any unusual thoughts, especially if they are new or getting worse quickly.

If you or your child have been using this medicine for a long time and you think you may have become mentally or physically dependent on it, check with your doctor. Some signs that you may be dependent on dextroamphetamine are:

• A strong desire or need to continue taking the medicine.
• A need to increase the dose to receive the effects of the medicine.
• Withdrawal effects (for example, mental depression, nausea or vomiting, stomach cramps or pain, trembling, unusual tiredness or weakness) that occur after the medicine is stopped.

This medicine may cause slow growth in children. If your child is using this medicine, the doctor will need to keep track of your child's height and weight to make sure that your child is growing properly.

This medicine may cause a condition called Raynaud phenomenon. Check with your doctor right away if you or your child have tingling or pain in the fingers or toes when exposed to cold, paleness or a cold feeling in the fingertips and toes, or a skin color change in your fingers.

Check with your doctor right away if you or your child have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.

If you or your child will be taking this medicine in large doses for a long time, do not stop taking it without first checking with your doctor. Your doctor may want you or your child to gradually reduce the amount you are taking before stopping it completely.

Before you have any medical tests, tell the medical doctor in charge that you or your child are taking this medicine. The results of some tests may be affected by this medicine.

Zenzedi® (dextroamphetamine sulfate tablets, USP) is indicated for:

Serious Cardiovascular Events

Children and Adolescents

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. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

Adults

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs (see CONTRAINDICATIONS).

Stimulant medications cause a modest increase in average blood pressure (about 2 to 4 mmHg) and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia (see CONTRAINDICATIONS).

Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.

Psychiatric Adverse Events

Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.

Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3,482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.

Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of, or worsening of, aggressive behavior or hostility.

Long-Term Suppression of Growth

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

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.

Peripheral Vasculopathy, Including Raynaud's Phenomenon

Stimulants, including Zenzedi, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulcerations and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Serotonin Syndrome

Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort [see Drug Interactions]. Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism [see CLINICAL PHARMACOLOGY]. The potential for a pharmacokinetic interaction exists with the coadministration of CYP2D6 inhibitors which may increase the risk with increased exposure to Zenzedi. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see Drug Interactions].

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Concomitant use of Zenzedi with MAOI drugs is contraindicated [see CONTRAINDICATIONS].

Discontinue treatment with Zenzedi and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Zenzedi with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Zenzedi with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.

Visual Disturbance

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

NDC 24338-851-10
100 tablets

Zenzedi™ CII
Dextroamphetamine
Sulfate Tablets, USP

Rx only
5 mg

PHARMACIST: Dispense the Medication
Guide provided separately to each patient.

Mfd. for: Arbor Pharmaceuticals, LLC
Atlanta, GA 30328

NDC 24338-854-10
100 tablets

Zenzedi® CII
Dextroamphetamine
Sulfate Tablets, USP

Rx only
15 mg

PHARMACIST: Dispense the Medication
Guide provided separately to each patient.

Mfd. for: Arbor Pharmaceuticals, LLC
Atlanta, GA 30328

NDC 24338-856-10
100 tablets

Zenzedi® CII
Dextroamphetamine
Sulfate Tablets, USP

Rx only
30 mg

PHARMACIST: Dispense the Medication
Guide provided separately to each patient.

Mfd. for: Arbor Pharmaceuticals, LLC
Atlanta, GA 30328

Applies to dextroamphetamine: oral capsule extended release, oral solution, oral tablet

Along with its needed effects, dextroamphetamine (the active ingredient contained in Zenzedi) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking dextroamphetamine:

• Agitation
• delusions
• seeing, hearing, or feeling things that are not there

• Blurred vision
• chest discomfort or pain
• difficulty breathing
• dizziness
• faintness
• false or unusual sense of well-being
• fast, pounding, or irregular heartbeat or pulse
• headache
• pounding in the ears
• shakiness in the legs, arms, hands, or feet
• swelling of the feet or lower legs
• trembling or shaking of the hands or feet
• twitching, twisting, or uncontrolled repetitive movements of the tongue, lips, face, arms, or legs
• unable to sleep
• uncontrolled vocal outbursts and/or tics (uncontrolled repeated body movements)
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur while taking dextroamphetamine:

• Change in consciousness
• dark-colored urine
• diarrhea
• discouragement
• feeling sad or empty
• fever
• irritability
• lack of appetite
• loss of consciousness
• loss of interest or pleasure
• mood or mental changes
• muscle cramps or spasms
• muscle pain or stiffness
• nausea
• panic state
• physical attempt to injure
• rapid breathing
• seizures
• stomach cramps
• sweating
• trouble concentrating
• violent actions
• vomiting

Some side effects of dextroamphetamine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bad, unusual, or unpleasant (after) taste
• change in taste
• constipation
• decreased interest in sexual intercourse
• dry mouth
• hives or welts, itching, or skin rash
• inability to have or keep an erection
• indigestion
• loss in sexual ability, desire, drive, or performance
• passing of gas
• redness of the skin
• weight loss