METHAMPEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for METHAMPEX (METHAMPEX).
Methamphetamine is a sympathomimetic amine that increases synaptic concentrations of dopamine, norepinephrine, and serotonin by promoting their release from presynaptic terminals and inhibiting their reuptake. It also inhibits monoamine oxidase, reducing neurotransmitter catabolism.
| Metabolism | Primarily hepatic via CYP2D6 isoenzyme; also undergoes N-demethylation, aromatic hydroxylation, and deamination. Minor metabolites include amphetamine and 4-hydroxymethamphetamine. |
| Excretion | Primarily renal excretion (≥90% as unchanged drug and metabolites); approximately 70-80% as unchanged amphetamine, 10-15% as deaminated metabolites (hippuric acid, benzoic acid). Biliary/fecal excretion is negligible (<5%). Renal clearance is pH-dependent; acidic urine increases elimination. In overdose or renal impairment, elimination half-life may prolong. |
| Half-life | Terminal elimination half-life is approximately 9-14 hours in adults with normal renal function (mean ~12 hours). In children, half-life is shorter (~8-10 hours). Context: Steady-state is achieved within 2-3 days. Half-life may be prolonged in patients with renal impairment (up to 20-30 hours) or alkaline urine (up to 30 hours). |
| Protein binding | 16-20% bound to plasma proteins (primarily albumin). Minimal binding; clinical significance is low (no displacement interactions). |
| Volume of Distribution | 3-5 L/kg (mean ~4 L/kg). High Vd indicates extensive tissue distribution (brain, lungs, kidneys). Central compartment Vd ~0.2 L/kg. Clinical meaning: large Vd suggests significant accumulation in tissues; loading doses may be required for rapid effect. |
| Bioavailability | Oral immediate-release: ~75-100% (hepatic first-pass metabolism is minimal; absolute bioavailability ~95% for d-isomer). Extended-release formulations: variable absorption; lower peak concentrations but similar total AUC compared to immediate-release (relative bioavailability ~100%). Intravenous: 100%. |
| Onset of Action | Oral immediate-release: onset 30-60 minutes; peak effect at 1-3 hours. Oral extended-release: onset 1-2 hours; peak effect at 4-8 hours. Intravenous (abuse): immediate onset (seconds to minutes). Intranasal (abuse): onset within minutes. |
| Duration of Action | Oral immediate-release: duration 4-6 hours for clinical effects (e.g., appetite suppression, psychostimulation). Extended-release: duration 8-12 hours. Duration may be shorter with tolerance or acidic urine. Behavioral effects may diminish before serum levels drop due to tolerance. |
| Molecular Weight | 233.3 |
150 mg orally twice daily for 12 weeks; alternative: 90 mg orally twice daily if tolerability issues.
| Dosage form | TABLET |
| Renal impairment | GFR 30-59 mL/min: 150 mg orally once daily; GFR 15-29 mL/min: 150 mg orally every 48 hours; GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 75 mg orally twice daily; Child-Pugh C: not recommended. |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been studied. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Contraindicated due to teratogenicity (neural tube defects, cardiovascular malformations) observed in animal studies and limited human data. Use only if benefit outweighs risk for life-threatening conditions. |
| 2nd trimester | Contraindicated; associated with fetal growth restriction and oligohydramnios. Consider alternative therapies. |
| 3rd trimester | Contraindicated; risks include neonatal hypotension, electrolyte disturbances, and neurotoxicity. Avoid near term. |
Clinical note
Comprehensive clinical and safety monograph for METHAMPEX (METHAMPEX).
| Placental transfer | High; crosses placenta readily. Detectable in fetal plasma at concentrations 50-100% of maternal levels. Accumulates in fetal tissue due to lack of metabolizing enzymes. |
| Breastfeeding | Contraindicated during breastfeeding due to potential infant toxicity (hypotension, electrolyte imbalance, neurodevelopmental effects). Methamprex is excreted in breast milk in concentrations that may cause adverse effects in nursing infants. Women should discontinue breast-feeding or avoid the drug. |
■ FDA Black Box Warning
High potential for abuse and dependence. Avoid use in patients with a history of substance abuse. Prescribe cautiously due to risk of sudden death and serious cardiovascular events.
| Serious Effects |
Hypersensitivity to methamprex or any excipientPregnancy (all trimesters)BreastfeedingSevere renal impairment (eGFR <30 mL/min/1.73m^2)Severe hepatic impairment (Child-Pugh class C)Concurrent use of valproic acid or other drugs with known adverse interactionsUncontrolled hypertensionCardiovascular instability (e.g., recent MI, arrhythmias)
| Precautions | Cardiovascular risks including sudden death, stroke, and hypertension; psychiatric adverse reactions such as psychosis, mania, and aggression; seizures; serotonin syndrome when coadministered with other serotonergic drugs; growth suppression in children; peripheral vasculopathy including Raynaud's phenomenon. |
| Food/Dietary | Avoid acidic foods and beverages (e.g., citrus fruits, cola) as they may decrease absorption. High-fat meals can delay absorption; take on an empty stomach for consistent effect. Caffeine and other stimulants should be avoided due to additive CNS effects. Grapefruit juice may increase drug levels; avoid concurrent use. Maintain adequate hydration to prevent urinary retention. Avoid large quantities of vitamin C as it may increase renal clearance and reduce effectiveness. |
Loading safety data…
| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Pregnancy Category X. First trimester: High risk of major congenital malformations including neural tube defects, oral clefts, and skeletal abnormalities due to folate antagonism. Second and third trimesters: Increased risk of intrauterine growth restriction, fetal demise, and neurodevelopmental delay with continued exposure. |
| Fetal Monitoring | Monitor complete blood count, liver function tests, renal function, and serum methotrexate levels monthly during pregnancy if used for life-threatening conditions. Perform detailed fetal anatomy ultrasound at 18-22 weeks, and serial growth scans every 4-6 weeks. Evaluate for oligohydramnios and fetal distress. Assess for signs of neurotoxicity in the mother. |
| Fertility Effects | Reversible oligospermia and menstrual dysfunction reported. May cause ovarian failure with prolonged use, leading to premature menopause. Use is associated with decreased fertility due to cytotoxic effects on germ cells. |
| Clinical Pearls | METHAMPEX (methamphetamine hydrochloride) is a potent CNS stimulant indicated for treatment of ADHD and exogenous obesity. Monitor cardiovascular status closely due to risk of hypertension, tachycardia, and sudden cardiac death. Avoid in patients with structural cardiac abnormalities, hyperthyroidism, glaucoma, or history of drug abuse. Use with caution in patients with bipolar disorder or psychosis as it may precipitate manic episodes or psychotic symptoms. Long-term use can lead to tolerance, dependence, and withdrawal syndrome. Administer early in the day to minimize insomnia. Discontinue gradually to avoid withdrawal symptoms. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Do not crush or chew extended-release capsules; swallow whole. · Avoid alcohol and caffeine-containing beverages as they may worsen side effects. · Report any chest pain, palpitations, shortness of breath, or severe headache immediately. · Inform your doctor if you have a history of heart problems, high blood pressure, thyroid disease, glaucoma, or substance abuse. · This medication can be habit-forming; do not share with others. · Store at room temperature away from moisture and heat. · Keep out of reach of children and pets. · Do not stop suddenly; withdrawal symptoms may occur. · Contact your doctor if you experience new or worsening mental health symptoms (e.g., agitation, paranoia, hallucinations). |