ADDERALL XR 20
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADDERALL XR 20 (ADDERALL XR 20).
Adderall XR 20 is a combination of amphetamine enantiomers (dextroamphetamine and levoamphetamine). It increases synaptic levels of dopamine and norepinephrine by inhibiting their reuptake and promoting their release from presynaptic terminals.
| Metabolism | Amphetamine is primarily metabolized by CYP2D6 via oxidative deamination, hydroxylation, and N-dealkylation. Minor metabolism by CYP1A2, CYP3A4, and CYP2C19. |
| Excretion | Approximately 90% of an oral dose is excreted renally, with 30% as unchanged amphetamine and the remainder as metabolites (including hippuric acid, benzoic acid, and hydroxylated derivatives). Fecal/biliary excretion accounts for <10%. |
| Half-life | Approximately 10-13 hours for d-amphetamine and 13-15 hours for l-amphetamine in adults; in children, 9-11 hours. The extended-release formulation provides a prolonged therapeutic effect masking shorter elimination. |
| Protein binding | Approximately 16-20% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | About 3-4 L/kg (300 L for a 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is nearly 100% for immediate-release; for ADDERALL XR, absolute bioavailability is unchanged due to complete absorption, but the extended-release profile modifies time to peak. |
| Onset of Action | Oral: 1-2 hours for detectable effects; peak clinical effect at 3-4 hours post-dose. |
| Duration of Action | 10-12 hours due to the extended-release formulation; clinical effect may last up to 12 hours in some patients. Capsules contain immediate-release (half) and delayed-release (half) beads. |
20 mg orally once daily in the morning.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | GFR 15-29 mL/min: 10 mg orally once daily; GFR <15 mL/min: not recommended. |
| Liver impairment | Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: use not recommended. |
| Pediatric use | 6-12 years: initial 5 mg orally once daily, titrate by 5 mg weekly to max 20 mg once daily; 13-17 years: initial 10 mg orally once daily, titrate to max 20 mg once daily. |
| Geriatric use | Start at lowest dose (10 mg orally once daily) with cautious titration due to increased sensitivity and potential comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ADDERALL XR 20 (ADDERALL XR 20).
| Breastfeeding | Contraindicated during breastfeeding. Amphetamine is excreted into human milk (M/P ratio not established). Can cause irritability, poor feeding, and growth suppression in nursing infants. Alternative therapies recommended. |
| Teratogenic Risk | Pregnancy Category C. First trimester: Limited human data; animal studies show increased risk of cardiovascular malformations and spontaneous abortion. Second/third trimesters: Risk of preterm delivery, low birth weight, and neonatal withdrawal syndrome (hyperactivity, irritability, feeding difficulties). Avoid use unless potential benefit justifies risk. |
■ FDA Black Box Warning
Adderall XR has a high potential for abuse and dependence. Prolonged use may lead to drug dependence. Avoid in patients with a history of drug abuse. Misuse may cause sudden death or serious cardiovascular events.
| Serious Effects |
Hypersensitivity to amphetamine or other components; during or within 14 days of MAOI therapy; glaucoma; hyperthyroidism; moderate to severe hypertension; symptomatic cardiovascular disease; advanced arteriosclerosis; history of drug abuse; agitated states; use with other sympathomimetics.
| Precautions | Serious cardiovascular events (sudden death, stroke, MI) in patients with pre-existing structural cardiac abnormalities or other serious heart problems; blood pressure and heart rate increase; psychiatric adverse events (exacerbation of pre-existing psychosis, mania, aggressive behavior); long-term suppression of growth in children; seizures; peripheral vasculopathy (Raynaud's phenomenon); serotonin syndrome when used with serotonergic drugs; worsening of motor and phonic tics; potential for allergic reactions. |
| Food/Dietary |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and weight gain regularly. Assess fetal growth via ultrasound (risk of intrauterine growth restriction). Monitor neonatal for signs of withdrawal or toxicity (jitteriness, feeding problems). ECG recommended if maternal cardiac risk factors. |
| Fertility Effects | May reduce fertility in females due to hormonal alterations (e.g., increased prolactin, menstrual irregularities). For males, no definitive evidence of impaired fertility; case reports of erectile dysfunction or delayed ejaculation. Discontinuation may improve fertility. |
| High-fat meals may delay absorption; administer consistently relative to meals. Avoid excessive caffeine (coffee, tea, energy drinks) as it may exacerbate stimulant effects. Alcohol should be avoided. Grapefruit juice may increase amphetamine levels; limit consumption. |
| Clinical Pearls | ADDERALL XR 20 (mixed amphetamine salts extended-release) is indicated for ADHD. Onset is within 1-2 hours; duration ~10-12 hours. Do not crush or chew capsules. Monitor for cardiovascular effects, growth suppression in children, and potential for abuse. Avoid use with MAOIs within 14 days. Baseline and periodic ECG recommended in patients with cardiac risk factors. |
| Patient Advice | Take exactly as prescribed; do not increase dose or stop abruptly without consulting your doctor. · Swallow capsules whole; do not crush, chew, or open. If unable to swallow, sprinkle contents on applesauce and consume immediately without chewing. · Avoid alcohol; may increase CNS depression and risk of cardiovascular effects. · Report any chest pain, palpitations, shortness of breath, or signs of psychosis (hallucinations, paranoia) immediately. · May cause insomnia; take first dose in the morning. Avoid caffeine or other stimulants. · Store at room temperature away from moisture and heat. · Keep out of reach of children; may cause serious harm if taken inadvertently. |