Midazolam
Mechanism :
Midazolam is a short-acting benzodiazepine central nervous system (CNS) depressant. Benzodiazepines presumably exert their effects by binding at stereo specific receptors at several sites within the central nervous system. All benzodiazepines cause a dose-related central nervous system depressant activity.
Indication :
- Premedication
- Sedation for procedures
- Febrile seizure
- Epilepsy
- Anxiety
Contraindications :
Contraindicated in patients with a known hypersensitivity to the drug, in patients with acute narrow-angle glaucoma. Midazolam Injection is not intended for intrathecal or epidural administration due to the presence of the preservative benzyl alcohol in the dosage form.
Dosing :
Sedation:
Oral:
500-750 mcg/kg once, 20-30 mins before procedure, diluted by juice. Max: 20 mg.
IM:
100-150 mcg/kg. Max: 10 mg.
IV:
<6 months: 50 mcg/kg IV over 2-3 minutes. Titrate with small increments till clinical effect is attained.
6 months to 6 years:
50-100 mcg/kg IV over 2-3 minutes. Repeat every 2-3 mins as and when needed. Max: 6 mg.
6-12 years:
25-50 mcg/kg IV over 2-3 minutes. Repeat every 2-3 mins as and when needed. Max: 10 mg.
Anaesthesia:
Non-neonatal:
Loading dose: 50-150 mcg/kg IV over 2-3 minutes as and when needed. Continuous infusion: 1-2 mcg/kg/min IV infusion.
Neonatal:
Continuous infusion: 0.5 mcg/kg/min IV infusion
Status epilepticus:
IV initial bolus of 0.15-0.2 mg/kg followed by 1 mcg/kg/min and increase by 1 mcg/kg/min every 15 min until seizures stop. Max: 5 mcg/kg/min.
Buccal:
<6 month: 300 mcg/kg
6 month-1 year: 2.5 mg
1-4 years: 5 gm
5-9 years: 7.5 mg
>10 years: 10 mg
Adverse Effect :
Decreased respiratory rate and apnea, drowsiness, seizure like activity, nausea/vomiting, cough, pain at injection site, ataxia, irritability, light-headedness, dysarthria, disinhibition, confusion, hangover, headache, dizziness, blurred vision, depression and hallucinations. Withdrawal symptoms on long term usage: muscle cramps, tremor, irritability, convulsions and perceptual distortions.
Interaction :
Erythromycin and other Macrolide Antibiotics, Quinupristin/Dalfopristin and Cimetidine: Inhibit the metabolism of midazolam resulting in reduced clearance, prolonged half-life, and increased volume of distribution producing raised and prolonged plasma midazolam concentrations resulting in profound sedation.
Itraconazole, Ketoconazole, Efavirenz, Nelfinavir, Saquinavir. Indinavir, and . ritonavir: Markedly raise the plasma concentration of midazolam thereby increasing the sedative and amnesic effects.
Diltiazem and Verapamil: Markedly increase the plasma levels and the effects of midazolam.
Grapefruit juice: Can increase the bioavailability of oral midazolam.
Theophylline, Carbamazepine and Phenytoin: May antagonize the sedative effects of benzodiazepines.
Opiates, Anticonvulsants, Sedative Antihistamines, Antipsychotics, Antidepressants and other Anxiolytic/Sedative agents: Enhancement of central depressive effect may occur.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Use sparingly and titrate according to response. Only bolus doses, not continuous infusion |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unlikely to be dialysed. Dose as in GFR<10 mL/min |
| HD | Not dialysed. Dose as in GFR<10 mL/min |
| HDF/High flux | Unknown dialysability. Dose as in GFR<10 mL/min |
| CAV/VVHD | Unknown dialysability. Dose as in normal renal function |
Hepatic Dose :
Single dose (eg, induction): No dosage adjustment recommended; patients with hepatic impairment may be more sensitive compared to patients without hepatic impairment; anticipate longer duration of action.
Multiple dosing or continuous infusion: Expect longer duration of action and accumulation; based on patient response, dosage reduction likely to be necessary.