CENTRAX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CENTRAX (CENTRAX).
Binds to benzodiazepine site on GABA-A receptors, enhancing chloride ion influx and hyperpolarization of neurons, resulting in anxiolytic, sedative, and muscle relaxant effects.
| Metabolism | Hepatic via CYP3A4; active metabolite desmethyldiazepam (nordazepam) with long half-life. |
| Excretion | Renal (primarily as glucuronide conjugates; <1% unchanged); biliary/fecal: minimal (less than 5%). |
| Half-life | 60-120 hours (mean 100 hours); long half-life leads to accumulation upon multiple dosing and prolonged sedation. |
| Protein binding | 98-99% bound to albumin. |
| Volume of Distribution | 1.0-2.6 L/kg (mean 1.8 L/kg); extensive tissue distribution, indicating high lipophilicity and tissue sequestration. |
| Bioavailability | Oral: approximately 90-100%. |
| Onset of Action | Oral: 30-60 minutes; slower than diazepam due to intermediate lipophilicity. |
| Duration of Action | 24-48 hours; prolonged due to active metabolite (N-desalkylprazepam, half-life ~60-100 h), causing residual sedation. |
| Molecular Weight | 324.8 Da |
10-30 mg orally, 3-4 times daily.
| Dosage form | CAPSULE |
| Renal impairment | GFR 10-50 mL/min: administer 75% of normal dose; GFR <10 mL/min: administer 50% of normal dose. |
| Liver impairment | Child-Pugh class A: no adjustment; Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use. |
| Pediatric use | 0.5-1 mg/kg/day in divided doses every 6-8 hours; maximum 40 mg/day. |
| Geriatric use | Initiate at 5 mg 3-4 times daily; titrate cautiously due to increased sensitivity and risk of sedation. |
| 1st trimester | Avoid; potential risk of fetal malformations (cleft palate, cardiac defects) based on animal studies and limited human data. |
| 2nd trimester | Avoid; may cause neonatal withdrawal syndrome and floppy infant syndrome if used near term. |
| 3rd trimester | Avoid; third trimester use increases risk of neonatal respiratory depression, hypotonia, and withdrawal symptoms. |
Clinical note
Comprehensive clinical and safety monograph for CENTRAX (CENTRAX).
| Placental transfer | Centrax (prazepam) and its active metabolite (desmethyldiazepam) readily cross the placenta, with fetal plasma concentrations similar to maternal levels at term. |
| Breastfeeding | Centrax (prazepam) is excreted into breast milk in small amounts. However, long-acting benzodiazepines may accumulate in nursing infants, leading to sedation and feeding difficulties. Breastfeeding is not recommended due to the potential for infant sedation and impaired metabolism. |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death.
| Serious Effects |
Hypersensitivity to prazepam or any benzodiazepineNarrow-angle glaucomaMyasthenia gravisSevere liver impairmentRespiratory insufficiencySleep apnea syndromeConcurrent use with ketoconazole or itraconazole
| Precautions | Risk of dependence and withdrawal reactions; respiratory depression, especially with opioids; CNS depression; impaired psychomotor function; not recommended in severe hepatic impairment; use caution in elderly and debilitated patients. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase prazepam levels. Limit caffeine intake as it may reduce sedative effects. No significant food restrictions apart from alcohol. |
Loading safety data…
| Lactation Rating | L4 (Possibly Hazardous) |
| Teratogenic Risk | First trimester: Data insufficient; benzodiazepines generally associated with cleft palate risk. Second and third trimesters: Risk of floppy infant syndrome, withdrawal symptoms, and neonatal respiratory depression. Avoid during pregnancy, especially in first and third trimesters. |
| Fetal Monitoring | Monitor maternal sedation, respiratory status, and fetal growth and heart rate. Assess neonatal tone, feeding, and withdrawal symptoms postpartum. |
| Fertility Effects | No specific fertility data; benzodiazepines may affect menstrual cycle or libido. No known direct impact on fertility. |
| Clinical Pearls | CENTRAX (prazepam) is a long-acting benzodiazepine with a slow onset; not ideal for acute anxiety. Use with caution in elderly due to increased risk of falls and cognitive impairment. Avoid in severe hepatic impairment; consider dose reduction in mild-to-moderate hepatic disease. Monitor for tolerance and dependence; limit to short-term use (≤4 weeks). Do not discontinue abruptly; taper to prevent withdrawal seizures. |
| Patient Advice | Avoid alcohol and other CNS depressants while taking this medication. · Do not drive or operate heavy machinery until you know how CENTRAX affects you. · Take exactly as prescribed; do not increase dose without consulting your doctor. · Do not stop taking this medicine suddenly; your doctor will help you taper off. · Store at room temperature away from moisture and heat. · Report any suicidal thoughts or mood changes to your healthcare provider immediately. |