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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for METHAMPEX (METHAMPEX).
| Breastfeeding | Contraindicated during breastfeeding due to potential serious adverse reactions in the infant. Methotrexate is excreted in breast milk; M/P ratio approximately 0.08-0.37. Concentrations may accumulate in the nursing infant leading to toxicity. |
| 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. |
■ 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 |
Known hypersensitivity to methamphetamine or other sympathomimetics; concurrent use or within 14 days of MAO inhibitors; glaucoma; hyperthyroidism; agitated states; history of drug abuse; moderate to severe hypertension; advanced arteriosclerosis; symptomatic cardiovascular disease.
| 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. |
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| 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. |