AMPHETAMINE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Amphetamine is a central nervous system stimulant that promotes release of monoamines (dopamine, norepinephrine, and serotonin) from presynaptic terminals and inhibits their reuptake, leading to increased synaptic concentrations. It also reversibly inhibits monoamine oxidase (MAO) and may directly stimulate postsynaptic receptors.
| Metabolism | Amphetamine is metabolized in the liver via aromatic hydroxylation (CYP2D6), N-dealkylation, and deamination. Major metabolites include 4-hydroxyamphetamine and norephedrine. Excretion is primarily renal, with pH-dependent elimination. |
| Excretion | Primarily renal (70-80% as unchanged drug and metabolites); minor biliary/fecal (approximately 2-5%). Urinary pH-dependent: acidic pH enhances elimination, alkaline pH reduces it. |
| Half-life | Terminal elimination half-life: 10-13 hours (adults) for immediate-release formulations; prolonged to 12-14 hours in chronic use. Clinical context: Half-life correlates with duration of action; twice-daily dosing may be needed. |
| Protein binding | Approximately 15-40% bound, primarily to albumin. |
| Volume of Distribution | Vd: 3-5 L/kg. Indicates extensive tissue distribution, particularly in brain and lungs; clinical meaning: high Vd accounts for prolonged presence after cessation. |
| Bioavailability | Oral: approximately 75-100% (immediate-release lower due to first-pass metabolism). Inhalation: >90%. Intranasal: 70-80%. Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes (immediate-release); 1-2 hours (extended-release). Inhalation (smoked/vaporized): <5 minutes. Intravenous: 1-2 minutes. Intranasal: 5-15 minutes. |
| Duration of Action | Oral immediate-release: 4-6 hours. Oral extended-release: up to 12 hours. Inhalation/intravenous: 2-4 hours. Clinical note: Tolerance develops to anorectic and euphoric effects; duration may decrease with repeated use. |
5-60 mg/day orally, divided into 2-3 doses; immediate-release: initial 5 mg once or twice daily, increase by 5 mg increments weekly; extended-release: initial 20 mg once daily in the morning, increase by 10 mg weekly
| Dosage form | TABLET, ORALLY DISINTEGRATING, EXTENDED RELEASE |
| Renal impairment | GFR 30-89 mL/min: no adjustment; GFR 15-29 mL/min: reduce dose by 50%; GFR <15 mL/min or dialysis: avoid use |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: use with caution, consider 50% dose reduction; Child-Pugh C: avoid use |
| Pediatric use | Age 6-12 years: immediate-release 5 mg once or twice daily, increase by 5 mg weekly up to 60 mg/day; extended-release 20 mg once daily, increase by 10 mg weekly up to 60 mg/day. Age 13-17 years: immediate-release 10 mg once daily, increase by 10 mg weekly up to 60 mg/day; extended-release 20 mg once daily, increase by 10 mg weekly up to 60 mg/day |
| Geriatric use | Initial 5 mg once daily, increase by 5 mg increments at 1-2 week intervals; monitor for cardiovascular effects and agitation; maximum 40 mg/day |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause hypertensive crisis Alkalinizing agents increase urinary excretion and acidifying agents decrease it High potential for abuse and dependence.
| Breastfeeding | Amphetamine is excreted into breast milk with a milk-to-plasma ratio (M/P) of approximately 2.8-7.5. Peak milk concentration occurs 2-4 hours after dose. Infant exposure can cause irritability, poor feeding, and sleep disturbances. Use while breastfeeding is generally not recommended; if essential, avoid breastfeeding for 4-6 hours after dosing. |
| Teratogenic Risk | Amphetamine is associated with increased risk of premature delivery, low birth weight, and neonatal withdrawal syndrome. First trimester use may increase risk of congenital malformations (e.g., gastroschisis, cleft palate), though absolute risk is low. Second and third trimester exposure can cause fetal growth restriction, preterm labor, and placental abruption. Neonatal toxicity includes irritability, feeding difficulties, and tremors. |
■ FDA Black Box Warning
Amphetamine has a high potential for abuse, which may lead to dependence and serious cardiovascular events, including sudden death in patients with pre-existing structural cardiac abnormalities. Misuse may cause serious adverse events including sudden death.
| Common Effects | narcolepsy |
| Serious Effects |
["Advanced arteriosclerosis","Symptomatic cardiovascular disease","Moderate to severe hypertension","Hyperthyroidism","Known hypersensitivity or idiosyncrasy to amphetamine","Glaucoma","Agitated states","History of drug abuse","During or within 14 days following administration of MAO inhibitors (hypertensive crisis may result)"]
| Precautions | ["Serious cardiovascular events including sudden death in patients with structural cardiac abnormalities or other serious heart problems","Increased blood pressure and heart rate","Psychiatric adverse events including exacerbation of pre-existing psychosis, mania, or aggression","Seizures in patients with a history of seizures","Growth suppression with prolonged use in children","Peripheral vasculopathy including Raynaud's phenomenon","Serotonin syndrome when used with other serotonergic drugs","Abuse and dependence potential"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of preeclampsia; fetal growth via serial ultrasound; and neonatal withdrawal symptoms post-delivery. Also assess for maternal substance abuse and psychiatric comorbidities. |
| Fertility Effects | Amphetamine may impair fertility in both sexes. In males, it can cause erectile dysfunction and reduced sperm motility. In females, it may disrupt menstrual cycles and ovulation due to dopaminergic effects. Data are limited, but reversible upon discontinuation. |
| Food/Dietary | Avoid acidic foods and beverages (e.g., citrus fruits, cola, coffee) within 1 hour of taking amphetamine, as they can reduce absorption. High-fat meals may delay absorption of extended-release formulations. Avoid alcohol, as it can increase CNS depression and cardiovascular side effects. Grapefruit juice may interact; consult your doctor. |
| Clinical Pearls | Amphetamine is a central nervous system stimulant used for ADHD and narcolepsy. Monitor for cardiovascular adverse effects, including hypertension and tachycardia. Avoid in patients with structural cardiac abnormalities or history of drug abuse. Use with caution in patients with bipolar disorder or psychosis due to risk of exacerbation. Long-term use may lead to tolerance and dependence. Abrupt discontinuation can cause withdrawal symptoms like fatigue and depression. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Avoid taking late in the day to prevent insomnia; take the first dose in the morning. · Do not crush or chew extended-release capsules; swallow them whole. · Common side effects include loss of appetite, dry mouth, and trouble sleeping; report chest pain, shortness of breath, or mood changes to your doctor. · Amphetamine can be habit-forming; do not share your medication with others. · Store at room temperature away from moisture and heat. · Keep a list of all medications you take and share it with your healthcare provider. |