DORIDEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DORIDEN (DORIDEN).
Barbiturate-like sedative-hypnotic; acts on GABA-A receptors to enhance inhibitory neurotransmission, causing CNS depression.
| Metabolism | Hepatic via CYP450 (primarily CYP3A4) to inactive metabolites. |
| Excretion | Renal (accounting for approximately 80% of elimination, primarily as glucuronide conjugates and unchanged drug); biliary/fecal (minor, about 10%). |
| Half-life | Terminal elimination half-life is 4-10 hours in healthy adults; prolonged in elderly and patients with hepatic impairment, increasing to 12-20 hours. |
| Protein binding | Approximately 55% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Vd is 0.7-1.2 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Oral: 70-80% due to first-pass metabolism. |
| Onset of Action | Oral: 30 minutes to 1 hour for hypnotic effect. |
| Duration of Action | Oral: 6-8 hours for hypnotic effect; residual sedation may occur due to prolonged half-life in some patients. |
500 mg orally at bedtime, maximum 1 g per day; for sedation, 250 mg 3 times daily after meals.
| Dosage form | CAPSULE |
| Renal impairment | In GFR 10-50 mL/min, administer 250 mg at bedtime; in GFR <10 mL/min, avoid use or reduce dose to 250 mg every 48 hours. |
| Liver impairment | In Child-Pugh class B, reduce dose by 50%; in Child-Pugh class C, avoid use due to risk of encephalopathy. |
| Pediatric use | Not recommended for pediatric use; no safe dosing established. |
| Geriatric use | Start at 125 mg at bedtime; increase cautiously to maximum 500 mg, as elderly are more sensitive to sedation and hypotension. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DORIDEN (DORIDEN).
| Breastfeeding | Doriden (glutethimide) is excreted into breast milk. M/P ratio not established. Due to risk of neonatal sedation and withdrawal, breastfeeding should be avoided during therapy. |
| Teratogenic Risk | First trimester: Increased risk of congenital malformations, particularly oral clefts and neural tube defects, based on animal studies and limited human data. Second and third trimesters: Potential for neonatal withdrawal syndrome (irritability, tremors, feeding difficulties) if used near term; also associated with transient neonatal respiratory depression. Use contraindicated during pregnancy. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to glutethimide or any component","Porphyria","Severe respiratory insufficiency","Concurrent use with other CNS depressants","Pregnancy (especially third trimester)"]
| Precautions | ["CNS depression may impair mental/physical abilities","Respiratory depression risk","Dependence and withdrawal symptoms","Rebound insomnia upon discontinuation"] |
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| Fetal Monitoring | Monitor fetal movements and heart rate pattern if inadvertent exposure. Assess neonate for signs of sedation, respiratory depression, and withdrawal (e.g., poor feeding, irritability). In maternal monitoring: assess for excessive sedation, hypotension, and dependency. |
| Fertility Effects | Animal studies have shown decreased fertility in males and females at high doses. Human data limited; potential for menstrual irregularities and reduced spermatogenesis based on similarity to barbiturates. |