DIAL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for DIAL (DIAL).
Benzodiazepine; potentiates GABA-A receptor activity, enhancing chloride ion influx and neuronal hyperpolarization.
| Metabolism | Hepatic via CYP3A4 and CYP2C19; active metabolite desmethyldiazepam. |
| Excretion | Primarily renal excretion of unchanged drug (60-70%) and minor fecal elimination (<10%). |
| Half-life | Terminal elimination half-life is 4-6 hours in healthy adults; prolonged to 12-24 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 85-95% bound primarily to albumin; binding decreased in uremia. |
| Volume of Distribution | 0.5-0.8 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Oral: 70-90% with first-pass metabolism reducing systemic availability; intravenous: 100%. |
| Onset of Action | Intravenous: 1-2 minutes; Oral: 15-30 minutes. |
| Duration of Action | Intravenous: 2-4 hours; Oral: 4-6 hours. Duration prolonged in hepatic impairment. |
| Action Class | Benzodiazepines |
| Brand Substitutes | Apex 2mg Tablet |
Intravenous: 10-20 mg initially, followed by 5-10 mg every 2-4 hours as needed; maximum cumulative dose 40 mg.
| Dosage form | SOLUTION |
| Renal impairment | GFR < 30 mL/min: reduce dose by 50% and extend interval to every 4-6 hours; GFR < 15 mL/min: use with caution, consider alternative. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: avoid use. |
| Pediatric use | Intravenous: 0.1-0.2 mg/kg/dose every 2-4 hours, maximum single dose 5 mg, maximum cumulative dose 10 mg/24 hours. |
| Geriatric use | Initiate at 50% of adult dose (2.5-5 mg IV), extend dosing interval to every 4-6 hours, monitor for excessive sedation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for DIAL (DIAL).
| Breastfeeding | Hydrochlorothiazide: Excreted in breast milk in small amounts (M/P ratio ~0.2); may suppress lactation. Hydralazine: Excreted in breast milk; M/P ratio not well established. Use with caution due to potential for adverse effects in nursing infants. Manufacturer recommends discontinuing breastfeeding or drug based on importance to mother. |
| Teratogenic Risk | DIAL is a brand name for a combination product containing hydrochlorothiazide and hydralazine. Hydrochlorothiazide: Crosses placenta; risk of fetal/neonatal jaundice, thrombocytopenia, electrolyte disturbances. Avoid in pregnancy-induced hypertension due to decreased plasma volume. Hydralazine: No well-controlled studies; associated with maternal hypotension and potential fetal distress. First trimester: Not recommended unless clearly needed. Second/third trimesters: Use only if benefit outweighs risk; monitor fetal heart rate. FDA Pregnancy Category C. |
■ FDA Black Box Warning
Concomitant use with opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for patients for whom alternative treatment options are inadequate.
| Serious Effects |
["Hypersensitivity to benzodiazepines","Severe respiratory insufficiency","Myasthenia gravis","Sleep apnea syndrome","Severe hepatic impairment"]
| Precautions | ["Risk of dependence and withdrawal","Respiratory depression","CNS depression","Use caution in hepatic impairment","Elderly patients more sensitive"] |
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| Fetal Monitoring | Monitor maternal blood pressure, serum electrolytes, renal function, and signs of lupus-like syndrome (hydralazine). Fetal monitoring: ultrasound for growth, amniotic fluid index, and non-stress test in third trimester. Neonatal monitoring: electrolytes, bilirubin, platelet count. |
| Fertility Effects | No specific studies on fertility in humans. Hydrochlorothiazide may cause erectile dysfunction in males; hydralazine has no known direct fertility effects. Theoretical risk of antihypertensive-induced placental hypoperfusion affecting fertility outcomes. Advise preconception counseling for hypertensive women. |