Diazepam
Stesolid · Stesolid Novum · Diazepam Accord · Diazepam Renaudin
The benzodiazepine with two faces. As a single dose in seizures it is fast and reliable — high lipid solubility gives onset within a couple of minutes intravenously, and the rectal solution works when no intravenous access is available. As standing treatment it is something entirely different: the parent compound has a half-life of one to two days and the active metabolite desmethyldiazepam up to four, so the concentration continues to rise for a week after initiation. That long tail is simultaneously the point in withdrawal treatment, where it provides a smooth self-tapering.
Rapid intravenous injection causes respiratory depression, blood pressure fall, and apnoea — never inject faster than 5 mg/min and have airway equipment available. The combination with opioids is the most common cause of fatal respiratory depression in benzodiazepine treatment.
Dosing in adults
| Indication | Regimen | Comment |
|---|---|---|
| Status epilepticus, iv | 10 mg iv (0,15–0,20 mg/kg), maximum 5 mg/min, repeated once after 10 min | maximum cumulative dose 20 mg before proceeding to fosphenytoin or levetiracetam |
| Seizures without iv access, rectal | 10 mg rectal solution in adults, repeated after approximately 10 min if needed | 5 mg in the elderly, frail patients, and children under 12 years |
| Alcohol withdrawal | 10 mg orally 3–4 times day 1, then halve the daily dose each day for 4–5 days | the long half-life provides a built-in taper — no additional tapering schedule is needed |
| Muscle spasm and spasticity | 5–10 mg orally 2–3 times daily | sedation is dose-limiting long before the muscle-relaxing effect |
| Anxiety, short-term | 2–10 mg orally 2–4 times daily, lowest effective dose | halve the dose in the elderly — or choose oxazepam instead |
No established dose adjustment by eGFR, but the renally excreted glucuronide metabolites accumulate in severe renal failure and sedation can be prolonged. Reduce the dose and extend the dosing interval at eGFR below 30 ml/min.
Diazepam is oxidatively metabolised via CYP2C19 and CYP3A4, and both clearance and metabolite turnover fall sharply in hepatic failure — the half-life may be multiplied several times. Avoid in severe hepatic failure and risk of hepatic encephalopathy; choose oxazepam, which is directly glucuronidated.
Rectal solution in seizures: 5 mg for children under 12 years or under 15 kg, 10 mg for children over 12 years. Intravenous 0,1–0,3 mg/kg slowly, maximum 10 mg, may be repeated once.
Avoid diazepam as standing treatment in the elderly. The half-life in an 80-year-old can be several days and the active metabolite desmethyldiazepam even longer, so the concentration continues to rise for up to a week after initiation — the patient who was alert on day two falls on day six, and the link to the tablet is missed because the dose was never increased. When a benzodiazepine is needed in this group, oxazepam is almost always the right choice.
Pharmacokinetics
- ONSET
- 1–3 min iv · 5–10 min rectal · 30–60 min oral
- DURATION
- 15–60 min clinical effect after a single iv dose
- BIOAVAIL.
- approximately 90 % oral · 80–90 % rectal · unpredictable im
- Vd
- 0,8–1,5 l/kg, high lipid solubility
- t½
- 20–50 hours (up to 100 hours in the elderly)
- ACTIVE METABOLITE
- Desmethyldiazepam, t½ 40–100 hours
- METABOLISM
- CYP2C19 and CYP3A4
- EXCRETION
- Renal as glucuronides