ADZENYS XR-ODT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADZENYS XR-ODT (ADZENYS XR-ODT).
Adzenys XR-ODT contains amphetamine, a central nervous system stimulant that increases extracellular levels of dopamine and norepinephrine by inhibiting their reuptake and promoting their release from presynaptic terminals.
| Metabolism | Amphetamine is metabolized primarily by cytochrome P450 2D6 (CYP2D6) and to a lesser extent by CYP2C19, with involvement of monoamine oxidase (MAO) pathways for deamination. |
| Excretion | Renal: approximately 90% as unchanged drug and metabolites (30%-40% as amphetamine, 40%-50% as hippuric acid and benzoic acid). Fecal: <4%. Biliary: negligible. |
| Half-life | Approximately 9-14 hours in adults, 8-11 hours in children (6-12 years). Extended-release pharmacokinetics produce a longer clinical duration compared to immediate-release formulations. |
| Protein binding | Approximately 16% bound to plasma proteins (albumin). |
| Volume of Distribution | Apparent Vd approximately 3.0-4.5 L/kg, indicating extensive tissue distribution. Large Vd reflects high lipophilicity and accumulation in tissues such as brain. |
| Bioavailability | Absolute oral bioavailability not established; relative bioavailability is high. ODT formulation has comparable AUC to immediate-release tablets. Food does not significantly affect bioavailability but may delay Tmax by about 1 hour. |
| Onset of Action | Orally disintegrating tablet (ODT): onset within 30-60 minutes following oral administration. |
| Duration of Action | Duration of clinical effect approximately 10-12 hours with XR-ODT formulation, designed for once-daily morning dosing. Due to extended-release technology, plasma concentrations remain therapeutically relevant for up to 12 hours. |
| Molecular Weight | 135.21 Da (amphetamine base) |
Initial: 9.4 mg orally once daily in the morning; titrate in increments of 9.4 mg per week based on tolerability and response. Maximum: 56.4 mg once daily.
| Dosage form | TABLET, ORALLY DISINTEGRATING, EXTENDED RELEASE |
| Renal impairment | GFR 30-89 mL/min: No adjustment needed. GFR <30 mL/min: Not recommended due to lack of data. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Initiate at 50% of normal dose and titrate cautiously. Child-Pugh C: Not recommended. |
| Pediatric use | Children 6-12 years: Initial: 9.4 mg orally once daily; titrate by 9.4 mg weekly; max 37.6 mg/day. Adolescents 13-17 years: Initial: 9.4 mg once daily; titrate by 9.4 mg weekly; max 56.4 mg/day. |
| Geriatric use | Start at lower end of dosing range (9.4 mg once daily) due to increased sensitivity and risk of adverse effects; titrate slowly. |
| 1st trimester | Amphetamines are considered to have a potential for teratogenic effects based on animal studies and limited human data. Use only if potential benefit justifies potential risk. |
| 2nd trimester | May be associated with increased risk of premature delivery and low birth weight. Monitor fetal growth. |
| 3rd trimester | Amphetamine use in the third trimester can lead to neonatal withdrawal symptoms and increased risk of preterm delivery. Avoid use near term. |
Clinical note
Comprehensive clinical and safety monograph for ADZENYS XR-ODT (ADZENYS XR-ODT).
| Placental transfer | Amphetamines cross the placenta; evidence from animal studies and human case reports. |
| Breastfeeding | Amphetamines are excreted into breast milk and may cause adverse effects in nursing infants, including irritability, poor feeding, and growth retardation. The American Academy of Pediatrics recommends use during breastfeeding only if clearly needed. Consider alternative therapies. |
■ FDA Black Box Warning
Adzenys XR-ODT has a high potential for abuse and misuse, which can lead to substance use disorder. Misuse may cause sudden death or serious cardiovascular adverse events.
| Serious Effects |
Hypersensitivity to amphetamines or any component of the formulationConcurrent use or within 14 days of MAO inhibitor therapyGlaucomaHypersensitivity to sympathomimetic aminesHistory of drug abuse
| Precautions | Serious cardiovascular events: sudden death in patients with structural cardiac abnormalities, stroke, myocardial infarction, hypertension. Assess cardiac status before use., Blood pressure and heart rate increases: monitor regularly., Psychiatric adverse events: exacerbation of pre-existing psychosis, manic episodes, aggressive behavior, new psychotic or manic symptoms., Seizures: may lower seizure threshold, use with caution in patients with history of seizures., Peripheral vasculopathy including Raynaud's phenomenon., Serotonin syndrome when co-administered with serotonergic drugs., Growth suppression: monitor height and weight during treatment., Priapism: seek immediate medical attention if prolonged erections occur., Visual disturbances: blurred vision. |
| Food/Dietary |
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| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | ADZENYS XR-ODT (amphetamine extended-release orally disintegrating tablet) is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, amphetamine (d- to l- ratio of 3:1) caused developmental toxicity at doses equivalent to the maximum recommended human dose. First trimester exposure may be associated with increased risk of cardiovascular malformations. Chronic exposure during the second and third trimesters may lead to fetal dependence, withdrawal, and premature delivery. Infants exposed in utero may exhibit symptoms such as irritability, dysphoria, and poor feeding. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and weight during pregnancy. Assess fetal growth via ultrasound. Monitor for signs of preterm labor. After delivery, observe the neonate for withdrawal symptoms, including irritability, hyperexcitability, poor feeding, and respiratory distress. |
| Fertility Effects | Amphetamines may impair fertility in both males and females based on animal studies, though human data are limited. Effects may be reversible upon discontinuation. Clinical relevance uncertain; consider impact on reproductive planning. |
| Avoid acidic foods and beverages (e.g., citrus fruits, fruit juices, cola) around the time of dosing as they reduce amphetamine absorption. High-fat meals may delay absorption but do not alter overall exposure. Maintain consistent food intake patterns to minimize variability in drug effect. |
| Clinical Pearls | ADZENYS XR-ODT is an extended-release orally disintegrating tablet of amphetamine, approved for ADHD in patients 6 years and older. Its pharmacokinetic profile allows once-daily dosing. Due to its immediate-release component, onset is similar to immediate-release amphetamine. Avoid administration with acidic foods or juices (e.g., orange juice) as they may reduce absorption. Monitor for rebound hyperactivity in the evening. Contraindicated in patients with glaucoma, hyperthyroidism, or history of drug abuse. Use with caution in patients with hypertension, seizures, or Tourette's syndrome. |
| Patient Advice | Take this medication exactly as prescribed; do not crush or chew the tablet. · The tablet will disintegrate quickly on the tongue; no water needed. · Avoid taking with fruit juices or vitamin C supplements as they may decrease effectiveness. · Do not take a dose in the late afternoon or evening to prevent insomnia. · This medication can be habit-forming; do not share with others. · Inform your doctor of all other medications, including over-the-counter and herbal supplements. · Report any chest pain, shortness of breath, or signs of serotonin syndrome (e.g., agitation, hallucinations, rapid heart rate). |