Phentermine
Phentermine
Generic Name
Phentermine
Mechanism
- Neurotransmitter release
- *Stimulates norepinephrine (NE)* release from locus ceruleus & dorsal vagal complex.
- *Inhibits dopamine reuptake* via dopamine transporter (DAT), slightly increasing dopaminergic tone.
- Appetite suppression
- Enhanced α‑adrenergic signaling activates melanocortin‑4 receptors (MC4R) in the hypothalamus, decreasing hypothalamic orexigenic POMC neurons.
- Reduced leptin‑mediated satiety signals.
- Energy expenditure
- Mild increase in basal metabolic rate (~3–7 % rise) from sympathetic stimulation.
Pharmacokinetics
- Absorption
- Rapid oral absorption: peak plasma concentration (Cmax) at ~1 h.
- Bioavailability ~70 % (minimal first‑pass effect).
- Distribution
- Plasma protein binding ~23 %.
- Volume of distribution ~0.8 L/kg; freely crosses the blood‑brain barrier.
- Metabolism
- Primarily hydroxylated by CYP2D6 to 4‑hydroxy‑phentermine; also N‑dealkylated.
- Metabolite active but significantly less potent than parent drug.
- Elimination
- Renal excretion (≈ >60 %) and biliary excretion.
- Half‑life 3–6 h (range 7–10 h in chronic use).
- Dose adjustment needed in severe renal impairment; CYP2D6 poor metabolizers may experience prolonged action.
Indications
- Obesity (BMI ≥ 30 kg/m²) or BMI ≥ 27 kg/m² with at least one weight‑related co‑morbid condition (e.g., type 2 diabetes, hypertension).
- Adjunct to dietary and lifestyle modification.
- Limited durations: typically ≤12 weeks; repeat courses allowed only when weight loss plateau and no adverse events.
Contraindications
| Category | Key Points |
| Contraindications |
• Pregnancy (class X); • Pheochromocytoma; • Untreated severe HTN; • Severe cardiovascular disease (MI, cardiac failure, arrhythmias); • Current or recent MAO‑I therapy (≥4 weeks). |
| Warnings |
• Cardiovascular risk – monitor BP, HR, ECG. • Psychiatric disorders – risk of irritability, insomnia, anxiety, depression. • QT prolongation with high doses or drug interactions. • Potential for misuse, dependence (AME classification I). |
| Precautions |
• Use with caution in patients with glaucoma, hyperthyroidism, and opioid use. • Cross‑reactions with other sympathomimetics (e.g., ephedrine). |
Dosing
| Form | Starting Dose | Maintenance Dose | Titration |
| Tablet (15 mg) | 15 mg once daily (morning) | 7.5–15 mg daily (split or single) | Increase by 2.5–5 mg increments every 1–2 weeks; max 35 mg/day. |
| Solution 30 mg/mL | 30 mg once daily | 15–30 mg/day | Same titration pattern. |
• Administration: Take 24 h before bedtime to reduce insomnia.
• Missed dose: No dose‑back-up; restart next day.
• Special populations: Start at lower end of range in elderly, hepatic/renal impairment.
Monitoring
| Parameter | Frequency | Rationale |
| Blood pressure & HR | Baseline, 2–3 weeks, then every 4–6 weeks | Sympathomimetic risk |
| Weight & BMI | Baseline, monthly | Efficacy & safety |
| ECG (QTc) | Baseline, 2–3 weeks (if high dose) | Detect QT prolongation |
| Liver enzymes (AST/ALT) | Baseline, every 3 months | Hepatic metabolism trace |
| Serum creatinine & eGFR | Baseline, every 3 months | Renal clearance |
| Adverse effect assessment | At each visit | Early detection of psychiatric or cardiac events |
| Pregnancy test | Initial & during treatment in females of childbearing potential | Teratogenic risk |
##Clinical Pearls**
• Timing matters – administer in the morning; instruct patients to shift to evening only if insomnia occurs.
• Low‑dose strategy: Many patients achieve >5 % weight loss on 7.5 mg daily; escalating beyond 15 mg offers diminishing returns vs toxicity.
• Use “buddy” points – pair with a calorie‑restricted diet (<1,500 kcal daily) and ≥30 min daily activity for maximal benefit.
• Screen for depression – baseline PHQ‑9; monitor at every visit to catch early suicidality.
• Dosing in renal impairment – no formal adjustment required, but counsel patients to report increased fatigue or palpitations.
• Drug interactions – avoid combining with other stimulants (e.g., decongestants, nicotine patches) unless carefully monitored.
• After‑care – if discontinuing, advise gradual taper (e.g., 2.5 mg reduction every 1–2 weeks) to mitigate rebound appetite increase.
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• Phentermine remains a valuable tool for obesity management, provided clinicians vigilantly monitor cardiovascular, psychiatric, and metabolic parameters, and employ a structured weight‑management regimen.