ADIPEX-P
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ADIPEX-P (ADIPEX-P).
Phentermine is a sympathomimetic amine that stimulates release of norepinephrine and to a lesser extent dopamine and serotonin from presynaptic nerve terminals in the hypothalamic feeding center, resulting in appetite suppression.
| Metabolism | Phentermine is primarily metabolized by liver CYP450 enzymes, including CYP3A4 and to a lesser extent CYP2D6. It undergoes N-oxidation, N-hydroxylation, and deamination to inactive metabolites. Approximately 70-80% is excreted unchanged in urine. |
| Excretion | Primarily renal (70-90% unchanged); minor biliary/fecal (10-30% as metabolites). Urinary pH-dependent; acidic urine increases excretion. |
| Half-life | Terminal half-life approximately 20-25 hours. Clinical context: Steady-state reached within 4-5 days; dosing adjustments may be needed in renal impairment. |
| Protein binding | ~50-60%, primarily to albumin and alpha1-acid glycoprotein. |
| Volume of Distribution | 3-4 L/kg; indicates extensive tissue distribution (e.g., brain, liver). |
| Bioavailability | Oral: ~90% (high first-pass metabolism, but systemic bioavailability remains high due to low hepatic extraction). |
| Onset of Action | Oral: 30-60 minutes for appetite suppression. |
| Duration of Action | 8-12 hours after immediate-release dosing; extended-release formulations up to 12-14 hours. Tolerance may develop with prolonged use. |
Phentermine (ADIPEX-P) is typically dosed as 15–37.5 mg orally once daily, administered 2 hours after breakfast or before breakfast. The 37.5 mg tablet is taken once daily before breakfast or 1–2 hours after breakfast; some patients may require 15 mg or 30 mg (half of a 37.5 mg tablet) once daily. The extended-release formulation (ADIPEX-P) is not available; only immediate-release tablets are marketed. Duration of therapy should be limited to a few weeks (e.g., 4–12 weeks) due to potential for tolerance and abuse.
| Dosage form | TABLET |
| Renal impairment | Phentermine is primarily renally excreted. In patients with severe renal impairment (CrCl <30 mL/min or eGFR <30 mL/min/1.73 m²), use is contraindicated. For moderate impairment (CrCl 30–60 mL/min), consider reducing dose to 15 mg once daily or extending dosing interval. No specific dose adjustments are provided for mild impairment (CrCl >60 mL/min). Monitor for accumulation and adverse effects. |
| Liver impairment | No specific dose adjustments are provided for hepatic impairment in the prescribing information. However, since phentermine is metabolized in the liver, caution is advised in patients with hepatic impairment. In severe hepatic impairment (Child-Pugh class C), avoid use due to lack of safety data. For moderate impairment (Child-Pugh B), consider a lower starting dose and monitor closely. Phentermine should be used with caution in patients with cirrhosis or other significant liver disease. |
| Pediatric use | Phentermine is not recommended for use in pediatric patients less than 16 years of age due to lack of safety and efficacy data. For adolescents 16 years and older, dosing is the same as adults: 15–37.5 mg orally once daily before breakfast or 1–2 hours after breakfast. The drug is not indicated for the treatment of obesity in adolescents without underlying comorbidities, and its use should be limited to short-term (a few weeks) as an adjunct to diet and exercise. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ADIPEX-P (ADIPEX-P).
| Breastfeeding | Excreted into breast milk; M/P ratio unknown. Contraindicated in breastfeeding due to potential for infant CNS stimulation and cardiovascular effects. Alternative agents preferred. |
| Teratogenic Risk | Pregnancy Category X: Contraindicated in pregnancy. First trimester: Risk of fetal malformations (e.g., neural tube defects) based on animal studies and limited human data. Second and third trimesters: Associated with increased risk of neonatal hypoglycemia, low birth weight, and withdrawal symptoms. No safe use established. |
■ FDA Black Box Warning
None.
| Serious Effects |
History of hypersensitivity to phentermine or other sympathomimetic amines; use within 14 days of MAOIs; history of drug abuse; cardiovascular disease (e.g., coronary artery disease, heart failure, arrhythmias, hypertension); hyperthyroidism; glaucoma; agitated states; pregnancy; breastfeeding.
| Precautions | Risk of pulmonary hypertension; valvular heart disease; primary pulmonary hypertension; dependence and tolerance; hypertension; tachycardia; CNS stimulation; psychiatric disorders (e.g., anxiety, insomnia); potential for abuse; risk of serotonin syndrome if used with other serotonergic drugs; risk of fetal harm if used during pregnancy; caution in patients with renal impairment. |
| Food/Dietary | Avoid alcohol, caffeine, and other stimulants (e.g., energy drinks) as they may increase cardiovascular side effects. High-fat meals may delay absorption; take on an empty stomach for best effect. |
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| Geriatric use | No specific dose adjustments are provided for elderly patients. However, due to the potential for age-related renal impairment, increased sensitivity to central nervous system effects (e.g., cardiovascular events, agitation), and possible concurrent diseases or medications, start with the lowest effective dose (e.g., 15 mg once daily) and monitor closely. Use is generally not recommended in elderly patients because of the risks of hypertension, tachycardia, and potential for abuse or dependence. Alternative weight loss strategies should be considered. |
| Fetal Monitoring |
| Monitor maternal blood pressure, heart rate, and signs of central nervous system stimulation. Assess fetal growth and well-being via ultrasound if inadvertent exposure occurs. Monitor for neonatal withdrawal symptoms if used near term. |
| Fertility Effects | Potential to impair fertility by inhibiting ovulation via central appetite suppression and neurotransmitter modulation. Reversible upon discontinuation. |
| Clinical Pearls | ADIPEX-P (phentermine) is a sympathomimetic amine anorectic indicated for short-term (≤12 weeks) management of exogenous obesity as an adjunct to caloric restriction. Avoid use in patients with history of cardiovascular disease, hyperthyroidism, glaucoma, or MAOI use within 14 days. Monitor for pulmonary hypertension and valvular heart disease with prolonged use. Due to abuse potential, it is a Schedule IV controlled substance. Discontinue if tolerance develops or if weight loss does not occur within 4 weeks. |
| Patient Advice | Take exactly as prescribed; do not increase dose or duration beyond 12 weeks. · Avoid taking late in the day to prevent insomnia; take early morning. · May cause dizziness or blurred vision; avoid driving if affected. · Report chest pain, palpitations, shortness of breath, or leg swelling immediately. · Do not use with other weight loss medications, MAOIs, or within 14 days of MAOI therapy. · Keep out of reach of children; store at room temperature away from moisture. · Pregnancy category X: avoid if pregnant or nursing; use effective contraception. |