PLACIDYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PLACIDYL (PLACIDYL).
Ethchlorvynol is a sedative-hypnotic that depresses the central nervous system at the level of the brainstem and reticular formation, potentiating GABAergic inhibition. Its exact molecular mechanism is not fully defined.
| Metabolism | Hepatic metabolism via glucuronidation and oxidative pathways; major metabolite is glucuronide conjugate. Unknown specific CYP enzymes. |
| Excretion | Primarily renal excretion of metabolites; less than 1% excreted unchanged. Biliary/fecal elimination accounts for 30-40% of metabolites, with enterohepatic recycling. |
| Half-life | Terminal elimination half-life is approximately 24 hours (range 10-40 hours), with prolonged elimination in hepatic impairment and overdose due to saturation of metabolism. |
| Protein binding | Approximately 90-95% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 4-6 L/kg, indicating extensive tissue distribution and accumulation in adipose tissue. |
| Bioavailability | Oral bioavailability is >90%, with rapid and nearly complete absorption from the gastrointestinal tract. |
| Onset of Action | Oral: 15-30 minutes (sedative/hypnotic effect). Onset is slower with food or in elderly patients. |
| Duration of Action | Duration of hypnotic effect is 4-6 hours, but residual sedation may persist for 12-24 hours due to long half-life and accumulation with repeated doses. |
500 mg to 1000 mg orally at bedtime, as a hypnotic. Usual dose is 500 mg to 750 mg. Maximum dose 1000 mg.
| Dosage form | CAPSULE |
| Renal impairment | Not recommended in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m²). For moderate impairment (eGFR 30-50 mL/min/1.73 m²), consider dose reduction by 50% and monitor for adverse effects. |
| Liver impairment | Contraindicated in Child-Pugh class C cirrhosis. For Child-Pugh class A or B, avoid use or reduce dose by 50% and monitor hepatic function; use with caution due to risk of hepatic encephalopathy. |
| Pediatric use | Not recommended for use in children due to lack of safety and efficacy data. |
| Geriatric use | Initiate with 250 mg orally at bedtime, titrate cautiously to 500 mg if needed. Monitor for excessive sedation, cognitive impairment, and falls. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PLACIDYL (PLACIDYL).
| Breastfeeding | Excreted in breast milk. M/P ratio not reported. Avoid breastfeeding due to potential neonatal accumulation and sedation. |
| Teratogenic Risk | First trimester: Case reports of congenital malformations (limb reduction defects, cleft palate) with high doses. Second/third trimester: Neonatal withdrawal syndrome (hyperexcitability, jitteriness, respiratory depression) at delivery. Risk category: X (contraindicated in pregnancy). |
| Fetal Monitoring |
■ FDA Black Box Warning
PLACIDYL is not indicated for chronic insomnia; prolonged use may lead to dependence and withdrawal symptoms. Risk of overdose and death with increasing doses.
| Serious Effects |
Hypersensitivity to ethchlorvynol, porphyria, acute intermittent porphyria, severe respiratory insufficiency, and pregnancy (especially first trimester).
| Precautions | May cause physical and psychological dependence; abrupt discontinuation after prolonged use may lead to withdrawal seizures. CNS depressant effects additive with alcohol and other sedatives. Caution in patients with hepatic or renal impairment, respiratory depression, and history of substance abuse. |
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| Fetal ultrasound for malformations if exposed early; neonatal abstinence syndrome monitoring for 48 hours after birth. |
| Fertility Effects | No documented effect on fertility in humans; animal studies show impaired reproductive function. |