PLEGINE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PLEGINE (PLEGINE).
Plegine (phendimetrazine) is a sympathomimetic amine that acts as an anorectic agent. It stimulates the hypothalamus to release norepinephrine and dopamine, thereby suppressing appetite. The exact mechanism is thought to involve the release of catecholamines from presynaptic nerve terminals in the lateral hypothalamic feeding center, leading to decreased food intake.
| Metabolism | Primarily hepatic via N-demethylation to the active metabolite phenmetrazine. Minor pathways include hydroxylation and conjugation. CYP450 enzymes involved include CYP3A4 and CYP2D6. |
| Excretion | Renal: 40% unchanged; Hepatic metabolism: 60% (biliary/fecal elimination of metabolites). |
| Half-life | Terminal elimination half-life: 4–8 hours (mean 6 hours). Clinical context: Steady-state achieved after 24–48 hours of repeated dosing. |
| Protein binding | 90% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd: 5–7 L/kg. Clinical meaning: High Vd indicates extensive tissue distribution, including CNS penetration. |
| Bioavailability | Oral: 40–60% (first-pass metabolism); Intramuscular: 90–100%. |
| Onset of Action | Oral: 30–60 minutes; Intramuscular: 10–20 minutes; Intravenous: 1–5 minutes. |
| Duration of Action | Oral: 6–12 hours; Intramuscular: 6–8 hours; Intravenous: 4–6 hours. Note: Duration depends on dose and patient factors; accumulation may occur with repeated dosing. |
25-50 mg orally once daily at bedtime, maximum 100 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: reduce dose by 50%; GFR <30 mL/min: use 25 mg every other day; not recommended in ESRD. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Children 6-12 years: 12.5-25 mg orally at bedtime; maximum 50 mg/day. Not recommended under 6 years. |
| Geriatric use | Initial dose 12.5 mg orally at bedtime; increase cautiously; monitor for sedation and anticholinergic effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PLEGINE (PLEGINE).
| Breastfeeding | Phendimetrazine is excreted in human milk. M/P ratio is unknown. Because of the potential for serious adverse reactions in nursing infants, such as irritability, poor feeding, and sleep disturbances, breastfeeding is contraindicated during therapy and for at least 48 hours after the last dose. |
| Teratogenic Risk | Plegine (phendimetrazine) is an anorectic sympathomimetic amine. There are no adequate and well-controlled studies in pregnant women. Animal reproduction studies have not been conducted with phendimetrazine. It should be used during pregnancy only if clearly needed. First trimester: Potential risks include fetal anomalies based on amphetamine-like effects; avoid due to unknown teratogenicity. Second and third trimesters: May cause fetal tachycardia, growth restriction, and withdrawal symptoms in neonates. Use is not recommended. |
■ FDA Black Box Warning
None (Phendimetrazine does not have a black box warning; however, it should be used cautiously due to potential for abuse and dependence.)
| Serious Effects |
History of drug abuse; advanced arteriosclerosis; symptomatic cardiovascular disease; moderate to severe hypertension; hyperthyroidism; glaucoma; agitated states; during or within 14 days of MAOI therapy; breastfeeding; pregnancy (category X).
| Precautions | Risk of abuse and dependence; tolerance may develop; use only for short-term (8-12 weeks); caution in hypertension, cardiovascular disease, hyperthyroidism, glaucoma, diabetes, and patients with a history of drug abuse; may impair ability to drive or operate machinery; potential for serious cardiovascular events; use with MAOIs may cause hypertensive crisis. |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and weight loss. Fetal monitoring includes ultrasound for growth restriction if used in pregnancy. Monitor neonatal heart rate and behavior for signs of withdrawal or sympathetic overstimulation if exposure occurred late in pregnancy. |
| Fertility Effects | Phendimetrazine may impair fertility by disrupting hypothalamic-pituitary-ovarian axis due to anorectic effects; weight loss can cause anovulation. Animal studies have not been reported. Clinical significance unknown; advise pregnancy planning due to potential risks. |