ADDERALL XR 5
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADDERALL XR 5 (ADDERALL XR 5).
Adderall XR 5 contains a combination of amphetamine and dextroamphetamine, which are central nervous system stimulants. They increase the levels of dopamine and norepinephrine in the synaptic cleft by inhibiting their reuptake and promoting their release from presynaptic neurons.
| Metabolism | Hepatic via CYP2D6 and to a lesser extent CYP3A4 and CYP1A2; also undergoes deamination and oxidation. |
| Excretion | Renal (approximately 90% as unchanged drug and metabolites, with 30-40% as unchanged amphetamine), fecal (minimal, <5%) |
| Half-life | d-Amphetamine: 10-13 hours (adults), 11-14 hours (children); l-Amphetamine: 13-15 hours (adults). The prolonged terminal half-life of the extended-release formulation supports once-daily dosing. |
| Protein binding | 20-40% bound, primarily to albumin. Binding is low and not clinically significant. |
| Volume of Distribution | Apparent Vd: 3-5 L/kg for d-amphetamine; 3-4 L/kg for l-amphetamine. Large Vd indicates extensive tissue distribution. |
| Bioavailability | Oral: Approximately 100% for Adderall XR (immediate-release and extended-release components combined; food may prolong Tmax but does not affect overall bioavailability). |
| Onset of Action | Oral: 30-60 minutes for initial effect from the immediate-release beads; maximal effect typically within 2-4 hours post-dose. |
| Duration of Action | Oral: Approximately 10-12 hours due to dual-pulse release (immediate-release and delayed-release beads), allowing once-daily dosing. |
| Molecular Weight | 135.21 |
20 mg orally once daily in the morning
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | eGFR 15-29 mL/min: reduce dose by 50%; eGFR <15 mL/min or dialysis: avoid use |
| Liver impairment | Child-Pugh Class B or C: reduce dose by 50% |
| Pediatric use | 6-12 years: start 5 mg once daily, titrate up to 20 mg; 13-17 years: start 10 mg once daily, titrate up to 20 mg |
| Geriatric use | Start at 5 mg once daily; monitor for cardiovascular effects and insomnia |
| 1st trimester | Avoid. Amphetamines are associated with increased risk of congenital malformations, particularly cardiac and orofacial clefts, based on human data. Use only if potential benefit justifies risk. |
| 2nd trimester | Caution. Risk of premature delivery, low birth weight, and neonatal withdrawal. Monitor fetal growth and maternal blood pressure. Use only if clearly needed. |
| 3rd trimester | Avoid in late pregnancy. May lead to neonatal withdrawal syndrome (irritability, feeding difficulties) and increased risk of maternal hypertension, preeclampsia, and preterm labor. |
Clinical note
Comprehensive clinical and safety monograph for ADDERALL XR 5 (ADDERALL XR 5).
| Placental transfer | Amphetamines cross the placenta readily. In vitro human placental perfusion studies show rapid clearance (CLpl approximately 10 mL/min). The fetal: maternal ratio is approximately 0.7-1.0, indicating significant fetal exposure. Ex vivo data confirm active transport via OCT and OCTN transporters. |
| Breastfeeding |
■ FDA Black Box Warning
High potential for abuse and dependence. Misuse may cause sudden death or serious cardiovascular events.
| Serious Effects |
Advanced arteriosclerosisSymptomatic cardiovascular diseaseModerate to severe hypertensionHyperthyroidismKnown hypersensitivity or idiosyncrasy to amphetaminesGlaucomaAgitated statesHistory of drug abuseDuring or within 14 days of MAOI therapy (risk of hypertensive crisis)
| Precautions | Sudden death and serious cardiovascular events, especially in patients with pre-existing structural cardiac abnormalities, Blood pressure and heart rate increase, Psychiatric adverse events (exacerbation of pre-existing psychosis, mania, aggression), Seizures (may lower seizure threshold), Serotonin syndrome risk when coadministered with serotonergic drugs, Long-term suppression of growth in children |
| Food/Dietary | Avoid high-fat meals or large amounts of vitamin C (e.g., citrus fruits) within 1 hour of dosing as they may alter absorption and efficacy. Maintain adequate hydration; acidic foods may decrease drug absorption. Grapefruit juice may increase amphetamine levels; limit consumption. |
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| Amphetamines are excreted into breast milk. With doses of 20-40 mg/day, infant exposure is approximately 2-8% of maternal weight-adjusted dose. Peak milk concentrations occur 2-4 hours after dose. In a study of 3 women, M/P ratio was 2.2-3.2. Infant serum levels may be detectable. Irritability, poor feeding, and insomnia have been reported in exposed infants. Consider infant monitoring and avoidance if possible. Alternative medications preferred. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | First trimester: Limited human data; animal studies show increased risk of cardiac malformations and cleft palate at high doses. Second and third trimesters: Risk of preterm delivery, low birth weight, and neonatal withdrawal syndrome (tremors, irritability). Overall: FDA Pregnancy Category C. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, weight gain, and signs of preeclampsia. Fetal: Ultrasound for growth restriction, amniotic fluid volume, and fetal heart rate monitoring in third trimester. Neonatal: Observe for withdrawal symptoms (tremors, irritability, hypertonia) for 48-72 hours after delivery. |
| Fertility Effects | In males: Potential sperm abnormalities (decreased motility, concentration) at therapeutic doses; reversible upon discontinuation. In females: Ovulation suppression may occur; return of normal fertility after cessation. No evidence of permanent infertility. |
| Clinical Pearls | ADDERALL XR 5 is a mixed amphetamine salt extended-release formulation. Monitor for cardiovascular adverse effects: check BP and HR at baseline and follow-up. Avoid in patients with structural cardiac abnormalities, cardiomyopathy, or serious arrhythmias. Use with caution in comorbid bipolar disorder or psychosis; may precipitate mixed/manic episode. Assess for history of drug abuse before prescribing due to high abuse potential. Discontinue if seizures develop. For pediatric patients, monitor growth; suppress appetite and weight loss are common. |
| Patient Advice | Take exactly as prescribed; do not crush or chew capsules; may sprinkle contents on applesauce if needed. · Avoid taking a dose in the late afternoon or evening to prevent insomnia. · Report any chest pain, shortness of breath, or fainting immediately. · Do not stop suddenly; taper under doctor supervision to avoid withdrawal. · Store at room temperature away from moisture and heat; keep out of reach of children. · Avoid alcohol while taking this medication. |