AMPHETAMINE SULFATE
Clinical safety rating: avoid
MAOIs can cause hypertensive crisis Alkalinizing agents increase urinary excretion and acidifying agents decrease it High potential for abuse and dependence.
Increases presynaptic release of dopamine and norepinephrine, blocks reuptake, and inhibits monoamine oxidase, resulting in CNS stimulation.
| Metabolism | Primarily hepatic via CYP2D6 and dopamine beta-hydroxylase; undergoes deamination and oxidation. |
| Excretion | Renal excretion of unchanged amphetamine (approximately 30-40%) and its metabolites; urinary pH-dependent: acidic urine enhances elimination (up to 70% unchanged), alkaline urine reduces it. Minor biliary/fecal elimination (<10%). |
| Half-life | Terminal elimination half-life: 10-13 hours in adults with acidic urine; prolonged to 16-34 hours with alkaline urine. In children, half-life is typically shorter (6-8 hours). |
| Protein binding | Approximately 15-40% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd: 3-5 L/kg, indicating extensive tissue distribution with high affinity for brain and lung tissues. |
| Bioavailability | Oral: >75% (complete absorption, but first-pass metabolism reduces bioavailability to ~75-90%). Immediate-release formulations have near-complete bioavailability relative to oral solution. |
| Onset of Action | Oral: onset within 30-60 minutes; peak effect at 1-3 hours. Intravenous: immediate. Inhalation (insufflation): rapid, within 5-15 minutes. |
| Duration of Action | Clinical effects last 4-6 hours for immediate-release formulations; extended-release formulations (e.g., Adderall XR) provide effects for 10-12 hours due to delayed release. |
| Molecular Weight | 135.21 |
5–60 mg/day orally in 1–3 divided doses, initial 5 mg once or twice daily, increase by 5 mg weekly.
| Dosage form | TABLET |
| Renal impairment | eGFR 30–59 mL/min: reduce dose by 50%; eGFR <30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Children ≥3 years: initial 2.5 mg once daily, increase by 2.5 mg weekly; max 40 mg/day in divided doses. |
| Geriatric use | Initial 2.5 mg once daily, increase slowly; monitor cardiovascular status and cognitive function. |
| 1st trimester | Amphetamine sulfate is FDA Pregnancy Category X. Use in the first trimester is contraindicated due to increased risk of congenital malformations, particularly cardiovascular and oral cleft defects. The drug has no established indication for use during pregnancy. |
| 2nd trimester | Continued use in the second trimester is contraindicated. Amphetamine can cause fetal toxicity, including intrauterine growth restriction, preterm delivery, and increased risk of placental abruption. |
| 3rd trimester | Use in the third trimester is contraindicated. Exposure can lead to neonatal withdrawal syndrome (irritability, feeding difficulties, tremors) and poor neonatal adaptation. Also associated with premature delivery and low birth weight. |
Clinical note
MAOIs can cause hypertensive crisis Alkalinizing agents increase urinary excretion and acidifying agents decrease it High potential for abuse and dependence.
| FDA category | Positive |
| Placental transfer |
■ FDA Black Box Warning
High potential for abuse and dependence. Misuse may cause sudden death or serious cardiovascular events.
| Common Effects | narcolepsy |
| Serious Effects |
Hypersensitivity to amphetamine or any component of the formulationConcurrent use or within 14 days of monoamine oxidase inhibitors (MAOIs)Advanced arteriosclerosisSymptomatic cardiovascular diseaseModerate to severe hypertensionHyperthyroidismGlaucomaAgitated statesHistory of drug abusePregnancy (category X)Lactation
| Precautions | Cardiovascular events (sudden death, stroke, MI), psychiatric adverse reactions (psychosis, mania), worsening of tics, growth suppression in children, seizures, peripheral vasculopathy (Raynaud's phenomenon), serotonin syndrome. |
| Food/Dietary | Avoid acidic foods and beverages (e.g., citrus fruits, juices, cola) as they can alter absorption and urine pH, affecting drug elimination. High-fat meals may delay absorption but not overall extent. Avoid alcohol and caffeine as they can exacerbate adverse effects. |
Loading safety data…
| Amphetamine readily crosses the placenta by passive diffusion and is detected in fetal circulation, achieving concentrations similar to maternal levels. Animal studies confirm placental transfer. |
| Breastfeeding | Amphetamine is excreted into breast milk in both high and variable concentrations. Use while breastfeeding is contraindicated due to potential stimulation and adverse effects in the nursing infant, including irritability, poor feeding, and insomnia. The manufacturer recommends discontinuing drug or discontinuing nursing, especially in long-term or high-dose use. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations (e.g., cardiac, oral clefts) based on amphetamine class effects. Second and third trimesters: Risk of fetal growth restriction, preterm birth, and neonatal withdrawal (e.g., irritability, poor feeding). Possible increased risk of placental abruption and intrauterine growth restriction. |
| Fetal Monitoring | Maternal: Blood pressure, heart rate, weight, and signs of abuse or dependence. Fetal: Serial ultrasound for growth, amniotic fluid volume, and fetal well-being (nonstress test or biophysical profile) in the second and third trimesters. Neonatal: Monitor for withdrawal symptoms (e.g., tremors, hypertonia) after delivery. |
| Fertility Effects | May impair female fertility via altered gonadotropin secretion and menstrual cycle irregularities. In males, may cause decreased libido and erectile dysfunction. Effects are generally reversible upon discontinuation. |
| Clinical Pearls | Monitor for signs of abuse, dependence, and cardiovascular effects (e.g., hypertension, tachycardia, arrhythmias). Avoid use in patients with structural cardiac abnormalities, cardiomyopathy, severe hypertension, or hyperthyroidism. Use with caution in patients with a history of seizures or bipolar disorder. Extended-release formulations should not be crushed or chewed. Renal impairment requires dose reduction. Drug interactions include MAOIs (hypertensive crisis), SSRIs/SNRIs (serotonin syndrome), and antacids (reduced absorption of amphetamine). |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Swallow extended-release capsules whole; do not crush, chew, or split them. · Avoid taking late in the day to prevent insomnia. · Do not stop abruptly; withdrawal symptoms may occur. · Report chest pain, shortness of breath, fainting, or signs of serotonin syndrome (e.g., agitation, hallucinations, rapid heart rate, fever, muscle twitching) immediately. · Inform your doctor of all medications you take, including over-the-counter drugs and herbal supplements. · This drug has a high potential for abuse; keep in a safe place and do not share with others. |