# Zenzedi ### (dextroamphetamine sulfate) **[Zenzedi](https://wiki.joshnp.com/books/drug-library/page/zenzedi)** (dextroamphetamine sulfate); CII
[**Full Prescribing Information**](https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=d6394df5-f2c9-47eb-b57e-f3e9cfd94f84&type=display)[**DailyMed Drug Information**](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6394df5-f2c9-47eb-b57e-f3e9cfd94f84)
--- ### **Summary** Zenzedi is an immediate-release, short-acting dextroamphetamine tablet approved for narcolepsy and for ADHD in patients aged 3 to 16. It is single-isomer dextroamphetamine, carrying no levoamphetamine and less peripheral noradrenergic load than an equivalent mixed-salt dose. Its differentiator is the age floor: 3 years is the lowest approved age in this library, and the seven-step ladder starting at 2.5 mg is what makes that band dosable. Schedule II; brand and generic. --- ### **Forms & Strengths** - **Tablets:** 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, 30 mg - **Scoring:** the 5 mg tablet is scored, the 10 mg tablet double scored --- ### **Dosing** - **Age:** - ADHD: 3-16 y/o, the lowest approved age here. Not recommended under 3 - Narcolepsy: no age bound stated; dose ladder given from age 6 - **Onset:** 30-60 min - **Duration:** 4-6 hours, the label's own redosing interval - **Initial Dose:** - ADHD, 3-5 y/o: 2.5 mg daily - ADHD, 6-16 y/o: 5 mg once or twice daily - Narcolepsy, 6-11 y/o: 5 mg daily - Narcolepsy, ≥ 12 y/o: 10 mg daily - **Titration:** - ADHD, 3-5 y/o: 2.5 mg at weekly intervals until optimal response - ADHD, 6-16 y/o: 5 mg at weekly intervals until optimal response - Narcolepsy, 6-11 y/o: 5 mg at weekly intervals - Narcolepsy, ≥ 12 y/o: 10 mg at weekly intervals - **Max Dose:** - ADHD, 6-16 y/o: 40 mg/day; only in rare cases will it be necessary to exceed this - ADHD, 3-5 y/o: no maximum stated in this label. Titrate to optimal response; 40 mg/day is not transferable downward to a preschooler - Narcolepsy: usual range 5-60 mg/day in divided doses - **Considerations:** First dose on waking, one or two further doses at 4 to 6 hour intervals; avoid late evening doses. The label directs interrupting treatment occasionally to test continued need. --- ### **Pharmacology** - **Mechanism:** Blocks reuptake at DAT and NET and promotes presynaptic catecholamine release via VMAT2 and TAAR1; the release component distinguishes amphetamines from methylphenidate - **Delivery / Release:** Immediate release. Cmax 36.6 ng/mL at about 3 hours, against 23.5 ng/mL at 8 hours for the SR capsule - **Formulation:** Single-isomer dextroamphetamine sulfate; no levoamphetamine - **Metabolism:** CYP2D6 to 4-hydroxyamphetamine. Half-life about 12 hours; the shorter duration is the peak-and-fall profile, not faster clearance - **Pharmacogenomics:** No genotype-directed dosing in the label; the actionable consequence is the CYP2D6-inhibitor interaction - **Class Positioning:** A higher earlier peak than [Dexedrine Spansule](https://wiki.joshnp.com/link/118), a finer ladder, and the 3 to 5 year band it lacks. Single-isomer where IR [Adderall](https://wiki.joshnp.com/link/8) is mixed salts --- ### **Indications** - **Narcolepsy** (ICD-10: G47.419): no age bound stated; dosing from age 6 - **ADHD** (ICD-10: F90.0, F90.1, F90.2, F90.8, F90.9): patients 3 to 16 y/o, within a total treatment program --- ### **Off-Label Uses** - **Preschool ADHD, where approval and guideline diverge** (ICD-10: F90.x): FDA approves from age 3; evidence for amphetamine in preschoolers is limited. - AAP places behavioral parent training first-line at 4 to under 6 (grade A) and names methylphenidate, not amphetamine, if medication is added (AAP 2019). - **ADHD at 17 and older** (ICD-10: F90.x): this label stops at 16; switch to a product with an adult indication. - **Binge eating disorder** (ICD-10: F50.81): lisdexamfetamine holds it, adults only; insufficient here. - **Where the evidence does not support use:** depression augmentation; no pediatric evidence for IR dextroamphetamine (AHRQ 2024). - **Cognitive enhancement without ADHD:** not an indication. --- ### **Contraindications & Warnings** - **Boxed Warning:** Abuse, misuse, and addiction; misuse can cause overdose and death. Assess abuse risk and monitor throughout. - **Contraindicated:** - Known hypersensitivity to amphetamine products - MAOI use, current or within 14 days - **Use with caution** (label Warnings, not contraindications): - Structural cardiac abnormality or serious arrhythmia; the label says avoid - Pre-existing hypertension; blood pressure and heart rate rise - Psychosis or bipolar disorder - Prior seizure or EEG abnormality - Peripheral vasculopathy including Raynaud phenomenon - Tics or Tourette syndrome, personal or family - Substance use disorder, patient or household - The 3 to 5 year band: no maximum stated, long-term pediatric effects not established. Hold at the lowest effective dose - **Screen before starting:** - Cardiac and family history of sudden death; ECG only if positive - Tics and Tourette syndrome, in child and family - Mania risk factors, including family history - Household abuse and diversion risk - Baseline height, weight, blood pressure and heart rate - Whether behavioral treatment has been tried, for any child under 6 (AAP 2019) --- ### **Drug Interactions** - **MAOIs** (phenelzine, tranylcypromine, selegiline, linezolid): hypertensive crisis and malignant hyperpyrexia, sometimes fatal. Do not give within 14 days. - **Serotonergic agents** (SSRIs, SNRIs, TCAs, triptans, fentanyl, lithium, tramadol): serotonin syndrome; counsel on symptoms and stop both if it occurs. - **CYP2D6 inhibitors** (paroxetine, fluoxetine, quinidine, ritonavir): raise exposure; start lower. - **Alkalinizing agents** (sodium bicarbonate, acetazolamide): raise absorption and reduce excretion; avoid or reduce the dose. - **Acidifying agents** (ascorbic acid, fruit juices, methenamine): lower absorption and raise excretion; adjust on response. - **Tricyclics** (desipramine, protriptyline): sustained rise in brain d-amphetamine; monitor. - **Antiepileptics** (phenytoin, phenobarbital, ethosuximide): delayed absorption; separate dosing, check levels after a stimulant change. - **Antihypertensives and antihistamines:** effects antagonised; recheck blood pressure, and do not rely on an antihistamine for sleep. - **Chlorpromazine and haloperidol:** inhibit the stimulant effect; expect loss of benefit. --- ### **Administration** - First dose on waking, further doses at 4 to 6 hour intervals. - Avoid late evening doses; a third dose in a young child costs sleep. - Splitting a scored tablet is legitimate for an intermediate dose where 2.5 mg is not stocked. - Prescribe at the lowest effective dosage. - Interrupt treatment occasionally to see whether therapy is still needed; this label makes that explicit. - If a dose is missed, skip it; do not double up. - Store securely, preferably locked, in a child-resistant container. --- ### **Side Effects** - **Common:** loss of appetite, weight loss, insomnia, overstimulation, restlessness, dry mouth, headache, dizziness, tremor, dysphoria, palpitations, raised blood pressure - **Serious:** - Sudden death with structural cardiac disease. Investigate exertional chest pain or syncope. - Psychotic episodes at recommended doses (rare), mania and new aggression. Consider discontinuing. - Serotonin syndrome. Stop both drugs and treat supportively. - Seizures. Discontinue. - Peripheral vasculopathy with digital ulceration. Reduce or stop. - Growth suppression. Interrupt if height or weight gain falls behind. - New or worsening motor and verbal tics. Discontinue if clinically appropriate. - Prolonged erections; painful erection beyond a few hours is a surgical emergency. --- ### **Monitoring & Labs** - **Cardiovascular:** heart rate and blood pressure at baseline, each dose change, and every 6 months. - **Growth, 6 to 16 y/o:** height, weight and BMI charted at baseline and every 6 months; interrupt if two percentile lines are crossed. - **Growth, 3 to 5 y/o:** height, weight and BMI at baseline and every 3 months; with no dose ceiling here, growth is the ceiling. - **Appetite and Sleep:** at every visit and dose change; ask when the last dose is given. - **Psychiatric and tics:** psychosis, mania, aggression and new tics at every visit. - **Peripheral vasculopathy:** inspect fingers and toes at every visit. - **Continued need:** schedule a deliberate interruption at least annually, per this label. - **Abuse and Diversion:** adherence, pill counts and PDMP check at every refill. - **Age boundary:** review the indication at the 17th birthday. No routine labs. --- ### **Discontinuation & Taper** - May be stopped abruptly at therapeutic doses; no taper is required. - Withdrawal after abrupt stop following prolonged use: dysphoria, fatigue, vivid dreams, increased appetite. - Rebound at 4 to 6 hours is offset, not withdrawal; the family may be describing the gap between doses. - **Planned interruption is a labelled instruction here:** stop occasionally to test whether symptoms recur at a level requiring continued therapy. - Interrupt treatment where growth or weight gain falls behind. --- ### **Pregnancy & Lactation** - **Pregnancy:** No adequate controlled studies; animal teratogenicity only far above human doses. Amphetamine-dependent mothers have more premature delivery and low birth weight. Use only if benefit justifies fetal risk. - **Lactation:** Label advises against nursing. LactMed: infant dose about 5.7% of the maternal weight-adjusted dose, all four infants studied growing normally. (LactMed 2025) - **Milk supply:** Dose-related prolactin suppression up to 40% may impair production before lactation is established. (LactMed 2025) - **Exposure Registry:** None on this label; the National Pregnancy Registry for Psychostimulants (1-866-961-2388) takes amphetamine exposures. --- ### **Counseling Points** - **Counsel the family on:** - The 4 to 6 hour window and the need for a second, sometimes third, dose. - For a preschooler: AAP puts behavioral parent training first and names a different class at that age. - For a preschooler: no maximum dose is set, so the growth chart is the ceiling, checked every three months. - The 2.5 mg tablet has only one generic supplier; if the pharmacy cannot fill it, split a scored 5 mg tablet. - The planned yearly interruption, so it is not heard later as doubt about the diagnosis. - Vitamin C and fruit juice can mimic treatment failure; bicarbonate and antacids raise levels. - Moving the largest meal to breakfast and to the evening. - Locked storage and the child-resistant container. - **Advise them to call for:** - Chest pain on exertion, fainting, or a racing heart that does not settle. - New hallucinations, or a young child describing things that are not there. - Numbness, coldness or colour change in the fingers or toes. - A new or markedly worse tic, or a seizure of any kind. - Weight loss, or shoes still fitting after several months. - A painful erection lasting more than a few hours. - Agitation, shivering, sweating or confusion after an antidepressant change. --- ### **References** 1. DailyMed. ZENZEDI (dextroamphetamine sulfate) tablets, USP prescribing information. Azurity Pharmaceuticals. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d6394df5-f2c9-47eb-b57e-f3e9cfd94f84 2. LactMed. Dextroamphetamine. Drugs and Lactation Database, National Institute of Child Health and Human Development. 2025. https://www.ncbi.nlm.nih.gov/books/NBK501740/ 3. openFDA. NDC Directory, generic\_name "dextroamphetamine". US Food and Drug Administration. 2026. https://api.fda.gov/drug/ndc.json 4. American Academy of Pediatrics. Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents. Pediatrics 144(4):e20192528. 2019. https://publications.aap.org/pediatrics/article/144/4/e20192528/81590/Clinical-Practice-Guideline-for-the-Diagnosis 5. Agency for Healthcare Research and Quality. ADHD Diagnosis and Treatment in Children and Adolescents. Comparative Effectiveness Review No. 267. 2024. https://www.ncbi.nlm.nih.gov/books/NBK602989/