PHENTERMINE HYDROCHLORIDE

Clinical safety rating: avoid

MAOIs can cause hypertensive crisis High potential for abuse and dependence.

How it works

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.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

MAOIs can cause hypertensive crisis High potential for abuse and dependence.

FDA category	Contraindicated
Breastfeeding	Excreted in breast milk; M/P ratio unknown. Potential for neonatal adverse effects (irritability, poor feeding, insomnia). Contraindicated during breastfeeding due to risk of infant exposure and lack of safety data.
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.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning exists for phentermine hydrochloride.

Side Effect Profile

Common Effects	Insomnia
Serious Effects

Absolute Contraindications

["History of cardiovascular disease (e.g., coronary artery disease, arrhythmias, stroke, uncontrolled hypertension)","Hyperthyroidism","Glaucoma","History of drug abuse","Use within 14 days of MAOIs","Pregnancy or breastfeeding","Hypersensitivity to phentermine or sympathomimetic amines"]

Clinical Precautions

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)."]

Clinical Tips & Counseling

Drug interactions

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PHENTERMINE HYDROCHLORIDE

Clinical safety rating: avoid

MAOIs can cause hypertensive crisis High potential for abuse and dependence.

How it works

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

MAOIs can cause hypertensive crisis High potential for abuse and dependence.

FDA category	Contraindicated
Breastfeeding	Excreted in breast milk; M/P ratio unknown. Potential for neonatal adverse effects (irritability, poor feeding, insomnia). Contraindicated during breastfeeding due to risk of infant exposure and lack of safety data.
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.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning exists for phentermine hydrochloride.

Side Effect Profile

Common Effects	Insomnia
Serious Effects