BENZEDRINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BENZEDRINE (BENZEDRINE).
Benzedrine (racemic amphetamine) releases dopamine and norepinephrine from presynaptic neurons, blocks their reuptake, and inhibits monoamine oxidase, increasing synaptic monoamine levels.
| Metabolism | Hepatic via CYP2D6 isoenzyme, deamination, and oxidation; inactive metabolites; renal excretion. |
| Excretion | Renal (30-40% unchanged, pH-dependent), with minor biliary/fecal elimination. At acidic urine pH, elimination half-life is shortened; at alkaline pH, reabsorption increases. |
| Half-life | Terminal elimination half-life: 4-6 hours in adults (range 4-8 hours). Clinically, duration of action correlates with half-life, but tolerance may develop with repeated dosing. |
| Protein binding | 16-20% bound, primarily to albumin. |
| Volume of Distribution | 2-4 L/kg, indicating extensive tissue distribution, particularly in the brain and lungs. |
| Bioavailability | Oral: 50-70% (due to first-pass metabolism); Inhalation: 60-90% (direct absorption across pulmonary epithelium); Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Inhalation (vapor): rapid, within minutes; Intravenous: immediate. |
| Duration of Action | Oral: 4-6 hours; Inhalation: 2-4 hours; Intravenous: 1-2 hours. Duration is dose-dependent and influenced by urine pH. |
Oral: 5-10 mg once or twice daily, maximum 40 mg/day. Intramuscular: 5-10 mg every 30-60 minutes as needed, maximum 40 mg/day.
| Dosage form | Tablet |
| Renal impairment | GFR 30-89 mL/min: No adjustment. GFR 15-29 mL/min: Reduce dose by 50%. GFR <15 mL/min: Avoid use. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 50%. Child-Pugh C: Avoid use. |
| Pediatric use | Oral: 0.1-0.5 mg/kg/dose once or twice daily, maximum 20 mg/day. Intramuscular: 0.1-0.2 mg/kg/dose every 30-60 minutes, maximum 20 mg/day. |
| Geriatric use | Start at 2.5 mg once or twice daily, titrate cautiously due to increased sensitivity and risk of adverse effects. Maximum 20 mg/day. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BENZEDRINE (BENZEDRINE).
| Breastfeeding | Contraindicated during breastfeeding; excreted into breast milk with M/P ratio ~3; associated with adverse effects in infants including irritability and poor feeding. |
| Teratogenic Risk | First trimester: Increased risk of cardiac malformations (VSD, PDA) and oral clefts; second and third trimesters: risk of intrauterine growth restriction, preterm delivery, and neonatal withdrawal syndrome. |
| Fetal Monitoring |
■ FDA Black Box Warning
Amphetamines have a high potential for abuse. Misuse may cause sudden death and serious cardiovascular adverse events.
| Serious Effects |
Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate-to-severe hypertension, hyperthyroidism, glaucoma, agitated states, history of drug abuse, during or within 14 days of MAOI therapy.
| Precautions | Serious cardiovascular events including sudden death, stroke, and myocardial infarction; psychiatric adverse reactions (exacerbation of psychosis, mania); hypertension; seizures; growth suppression in children; peripheral vasculopathy. |
| Food/Dietary | Avoid acidic beverages (e.g., fruit juices) within 1 hour of dosing as they may decrease absorption. High-fat meals can delay absorption of extended-release forms. Caffeine may exacerbate CNS stimulation. |
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| Monitor maternal blood pressure, heart rate, and fetal growth (ultrasound) ; assess for signs of preterm labor and neonatal withdrawal after delivery. |
| Fertility Effects | May impair fertility in males (reduced sperm count and motility) and females (ovulatory dysfunction) ; effects are reversible upon discontinuation. |
| Clinical Pearls | Benzedrine (racemic amphetamine) is a CNS stimulant; monitor for cardiovascular events, abuse potential, and growth suppression in children. Do not co-administer with MAOIs or within 14 days of MAOI use. Use with caution in patients with hypertension, hyperthyroidism, glaucoma, or history of substance abuse. |
| Patient Advice | May cause insomnia; take last dose early in the day to avoid sleeping difficulties. · Do not crush or chew extended-release capsules; swallow whole with water. · Report chest pain, palpitations, shortness of breath, or hallucinations immediately. · May suppress appetite; monitor weight and nutritional intake, especially in children. · Avoid alcohol and discuss all other medications with your doctor. · Store at room temperature away from moisture and heat; keep out of reach of children. |