METHAMPHETAMINE HYDROCHLORIDE
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.
Methamphetamine is a potent central nervous system stimulant that increases synaptic concentrations of dopamine, norepinephrine, and serotonin by reversing their transporters, inhibiting monoamine oxidase, and inhibiting vesicular monoamine transporter 2 (VMAT2).
| Metabolism | Primarily hepatic via CYP2D6, with some contribution from renal excretion. Metabolites include amphetamine and 4-hydroxymethamphetamine. |
| Excretion | Primarily renal excretion of unchanged drug (30-50%) and metabolites (p-hydroxymethamphetamine, amphetamine, p-hydroxyamphetamine). Up to 70% eliminated over 24 hours. Renal clearance depends on urinary pH; acidic urine (pH <5) increases elimination, alkaline urine reduces it. Biliary/fecal excretion is minimal (<5%). |
| Half-life | Terminal elimination half-life: 10-12 hours. Clinical context: Longer half-life than amphetamine (6-8 h) due to higher lipophilicity and tissue binding. Variability (4–30 h) depends on urine pH, dose, and chronic use (tissue accumulation). |
| Protein binding | Approximately 15-20% bound; primarily to albumin and alpha-1-acid glycoprotein. Low binding contributes to high free fraction and tissue distribution. |
| Volume of Distribution | 3-5 L/kg. Clinical meaning: Extensive tissue binding and high lipophilicity lead to large Vd, indicating deep tissue compartment (brain, lungs, liver). Accumulation in brain may exceed plasma concentrations >10-fold. |
| Bioavailability | Oral: 50-70% (first-pass metabolism reduces bioavailability). Smoking/inhalation: 90-100% (rapid pulmonary absorption bypasses hepatic metabolism). Intranasal: 70-90% (variable due to mucosal perfusion). |
| Onset of Action | Oral: 15-30 minutes (peak effect 1-3 h); Intravenous: immediate (<1 min); Smoking/inhalation: 5-10 seconds (rapid brain penetration); Intranasal: 3-5 minutes. |
| Duration of Action | Oral: 6-8 hours (core effects); high-dose or chronic users may experience prolonged effects (12-24 h) due to accumulation. Smoking/IV: acute effects 4-6 hours with rapid offset followed by dysphoria. Clinical note: Duration significantly reduced by acidic urine or tolerance. |
| Molecular Weight | 185.69 |
Oral: 5-10 mg once or twice daily, titrated up to a maximum of 60 mg/day in divided doses. Typical initial dose for ADHD: 5 mg once or twice daily, increase by 5 mg weekly; for obesity: 5 mg before meals, up to 30 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: Use 50% of usual dose; GFR <30 mL/min: Avoid use (not recommended). Hemodialysis: Not dialyzable; avoid use. |
| Liver impairment | Child-Pugh A: No adjustment needed; Child-Pugh B: Reduce dose by 50%; Child-Pugh C: Avoid use due to risk of hepatic encephalopathy. |
| Pediatric use | Children 6-12 years: Initial 5 mg once or twice daily, increase by 5 mg weekly up to 20-40 mg/day in divided doses. Adolescents: Same as adult dosing. Not recommended for children <6 years. |
| Geriatric use | Start at 2.5 mg once or twice daily, titrate slowly due to increased sensitivity and risk of cardiovascular or CNS effects. Avoid use in elderly with hypertension or cardiac disease. |
| 1st trimester | Teratogenic risk: associated with increased risk of congenital malformations (e.g., cleft palate, cardiac defects). Avoid use. |
| 2nd trimester | Increased risk of prematurity, low birth weight, and placental abruption. Avoid use. |
| 3rd trimester | Risk of neonatal withdrawal syndrome, irritability, and neurodevelopmental effects. Avoid use. |
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 | Readily crosses the placenta; fetal concentrations may exceed maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
High potential for abuse and dependence; misuse can cause serious cardiovascular events and sudden death.
| Common Effects | narcolepsy |
| Serious Effects |
Hypersensitivity to methamphetamine or sympathomimetic aminesCardiovascular disease (e.g., coronary artery disease, hypertension)HyperthyroidismGlaucomaAgitated statesHistory of drug abuseConcomitant MAOI therapy or within 14 days
| Precautions | Risk of abuse, dependence, and withdrawal; cardiovascular events (sudden death, stroke, myocardial infarction) especially in patients with structural cardiac abnormalities; psychiatric effects (psychosis, mania, aggression); seizures; serotonin syndrome when co-administered with serotonergic drugs; growth suppression in children; exacerbation of tics; peripheral vasculopathy including Raynaud's phenomenon. |
| Food/Dietary |
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| Methamphetamine is excreted into breast milk in high concentrations; peak milk levels may exceed maternal plasma levels. Neonatal exposure can cause irritability, agitation, and poor feeding. Breastfeeding is contraindicated during methamphetamine use. |
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | METHAMPHETAMINE HYDROCHLORIDE is classified as FDA Pregnancy Category C. First trimester: Increased risk of congenital anomalies, particularly cardiovascular defects, cleft palate, and neural tube defects based on animal studies and limited human data. Second and third trimesters: Associated with preterm birth, intrauterine growth restriction (IUGR), placental abruption, and fetal distress. Neonatal withdrawal syndrome (irritability, poor feeding, tremors) may occur. Chronic use may cause long-term neurodevelopmental deficits. |
| Fetal Monitoring | Monitor maternal blood pressure (risk of hypertension), heart rate, and evidence of preeclampsia. Fetal monitoring: serial ultrasound for fetal growth, amniotic fluid volume, and placental integrity (abruption risk). Nonstress test or biophysical profile as clinically indicated. Assess for preterm labor signs. Neonatal monitoring: observe for withdrawal symptoms (Finnegan scoring), growth parameters, and neurobehavioral assessment. |
| Fertility Effects | Methamphetamine use is associated with decreased fertility in both males and females. In males: reduced sperm count, motility, and increased morphological abnormalities; potential erectile dysfunction. In females: menstrual irregularities, anovulation, and impaired ovarian function. Chronic use may lead to hypothalamic-pituitary-gonadal axis disruption. Animal studies show delayed puberty and reduced reproductive organ weights. |
| Avoid acidic foods and beverages (e.g., citrus fruits, sodas) as they may decrease absorption. High-fat meals may delay absorption of extended-release formulations. Limit caffeine intake as it may exacerbate stimulant effects. Avoid tyramine-rich foods (aged cheeses, cured meats) in patients also taking MAOIs, as combination may cause hypertensive crisis. |
| Clinical Pearls | Monitor for signs of serotonergic toxicity (e.g., hyperthermia, rigidity) if co-administered with SSRIs, MAOIs, or other serotonergic drugs. Avoid use in patients with cardiovascular disease, hypertension, or hyperthyroidism. Methamphetamine has high abuse potential; prescribe only after verifying diagnosis of ADHD (F90.0) or exogenous obesity (E66.3) with strict adherence to scheduled use. Do not administer late in the day to prevent insomnia. Use with caution in patients with seizure disorders or bipolar disorder as it may lower seizure threshold or precipitate mania. ECG monitoring recommended if history of structural cardiac abnormalities. |
| Patient Advice | Take exactly as prescribed; never increase dose or frequency without consulting your doctor. · Do not crush, chew, or break extended-release capsules; swallow whole. · Avoid alcohol and caffeine while taking this medication. · Report chest pain, palpitations, shortness of breath, or fainting immediately. · This drug can be habit-forming; store in a secure place. · Do not stop abruptly; taper under medical supervision to avoid withdrawal. · Notify your doctor if you develop signs of serotonin syndrome (agitation, hallucinations, rapid heart rate, fever, muscle stiffness). · May cause dizziness or blurred vision; avoid driving until you know how it affects you. |