PHENTERMINE HYDROCHLORIDE
Clinical safety rating: avoid
MAOIs can cause hypertensive crisis High potential for abuse and dependence.
Phentermine is a sympathomimetic amine that acts as an appetite suppressant by stimulating the release of norepinephrine in the hypothalamus, leading to decreased food intake. It binds to adrenergic receptors, promoting satiety.
| Metabolism | Phentermine is primarily metabolized by the liver via N-oxidation and aromatic hydroxylation, with minor involvement of cytochrome P450 enzymes (CYP3A4). It also undergoes some renal elimination unchanged. |
| Excretion | Renal (80% unchanged, with remainder as metabolites); biliary/fecal minimal; renal clearance dependent on urine pH (alkaline urine reduces excretion). |
| Half-life | Terminal elimination half-life: 19–24 hours; clinical context: steady-state reached in 4–5 days. |
| Protein binding | Approximately 80% bound to plasma proteins (mainly albumin). |
| Volume of Distribution | 3–4 L/kg (3–4 L/kg); indicates extensive tissue distribution, including brain. |
| Bioavailability | Oral: approximately 90% (but interindividual variability; first-pass metabolism minimal). |
| Onset of Action | Oral: 30–60 minutes; peak effect 1–3 hours. |
| Duration of Action | Anorectic effect: 3–6 hours after a single oral dose; sustained with repeated dosing; clinical use: short-term (≤12 weeks) due to tolerance and potential dependence. |
| Molecular Weight | 203.67 |
15-37.5 mg orally once daily in the morning before breakfast or 1-2 hours after breakfast. Alternatively, 8 mg orally three times daily 30 minutes before meals.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (eGFR < 30 mL/min/1.73 m²). No dose adjustment required for mild to moderate impairment (eGFR ≥ 30 mL/min/1.73 m²). |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). Use with caution in moderate impairment (Child-Pugh class B); consider dose reduction or less frequent dosing. No adjustment needed for mild impairment (Child-Pugh class A). |
| Pediatric use | Not recommended for use in pediatric patients below 17 years of age. For adolescents ≥17 years, adult dosing may be used. |
| Geriatric use | Start at lowest dose (15 mg daily) and titrate cautiously due to increased sensitivity and higher risk of adverse effects (e.g., cardiovascular events). Monitor renal function and blood pressure. |
| 1st trimester | Avoid; associated with increased risk of congenital malformations, including neural tube defects and cardiac anomalies. |
| 2nd trimester | Avoid; may cause fetal harm due to sympathomimetic effects, including reduced uterine blood flow. |
| 3rd trimester | Avoid; may cause neonatal withdrawal symptoms and pulmonary hypertension. |
Clinical note
MAOIs can cause hypertensive crisis High potential for abuse and dependence.
| FDA category | Contraindicated |
| Placental transfer | Crosses placenta; detected in fetal tissues. |
| Breastfeeding | Excreted into breast milk; potential for infant stimulation, irritability, and poor feeding. Use not recommended. |
■ FDA Black Box Warning
No FDA black box warning exists for phentermine hydrochloride.
| Common Effects | Insomnia |
| Serious Effects |
Hypersensitivity to phentermineHistory of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias)HyperthyroidismGlaucomaAgitated statesHistory of drug abuseConcurrent or within 14 days of MAOI therapy
| Precautions | Risk of primary pulmonary hypertension (PPH) and valvular heart disease, especially with concurrent use of serotonergic drugs or history of heart disease., Potential for drug dependence and abuse; use only for short-term (up to 12 weeks)., May increase blood pressure and heart rate; monitor cardiovascular status., Risk of serotonin syndrome when combined with other serotonergic agents (e.g., SSRIs, MAOIs). |
| Food/Dietary |
Loading safety data…
| Lactation Rating | L4 |
| Teratogenic Risk | FDA Pregnancy Category X. Contraindicated in pregnancy. First trimester: Increased risk of congenital anomalies (orofacial clefts, neural tube defects) reported in animal studies and human case series. Second and third trimesters: Risk of fetal growth restriction, preterm birth, and neonatal withdrawal. No safe use established. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and signs of CNS stimulation. Fetal ultrasound for growth and anomalies if inadvertent exposure occurs. Consider ECG for maternal cardiovascular assessment. |
| Fertility Effects | May impair fertility in females via disruption of hypothalamic-pituitary-ovarian axis; reversible on discontinuation. No data on male fertility effects. |
| Avoid concurrent consumption of caffeine or other stimulants (e.g., energy drinks, coffee, tea) to minimize additive sympathomimetic effects. Alcohol may enhance CNS depression or hypotension; limit intake. High-fat meals may delay absorption; take on an empty stomach. Avoid large amounts of tyramine-rich foods (e.g., aged cheese, cured meats) if also taking MAOIs. |
| Clinical Pearls | Phentermine is a sympathomimetic amine indicated for short-term (≤12 weeks) adjunct to lifestyle modification for obesity (BMI ≥30 or ≥27 with comorbidity). It is contraindicated in patients with cardiovascular disease, hyperthyroidism, glaucoma, or history of drug abuse. Avoid coadministration with MAOIs or within 14 days; risk of hypertensive crisis. Monitor blood pressure and heart rate; discontinue if significant elevations occur. Tolerance may develop; if no weight loss after 4 weeks, discontinue. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose. · Avoid taking late in the day to prevent insomnia. · Report chest pain, palpitations, shortness of breath, or leg swelling immediately. · Do not use if you have heart disease, high blood pressure, or glaucoma. · Inform your doctor about all medications, especially MAOIs, antidepressants, or stimulants. · This medication is for short-term use only; combine with diet and exercise. · May cause dizziness or blurred vision; avoid driving until you know how it affects you. · Do not stop abruptly; taper as directed to avoid withdrawal symptoms. |