Oral, Intravenous (IV), Intramuscular (IM), Intranasal, Buccal, Rectal
- Injection (IV/IM): 1 mg/mL, 5 mg/mL (ampoules/vials)
- Intranasal spray: 5 mg/dose (nasal spray device)
- Buccal solution: 2.5 mg/0.5 mL, 5 mg/mL, 7.5 mg/1.5 mL, 10 mg/2 mL
INDICATIONS + DOSING — FOR CLINICIAN USE ONLY
Primary Indications (Approved / Standard in India)
- Procedural Sedation (Endoscopy, Minor Surgery, Diagnostic Procedures)
Parameter Recommendation
Starting dose 1–2 mg IV (administer slowly over 2–3 minutes)
Titration Additional 0.5–1 mg IV every 2–3 minutes until adequate sedation achieved
Usual maintenance dose 2–5 mg IV total for procedure
Maximum dose 5 mg IV in healthy adults; reduce to 2–3 mg in elderly or debilitated patients
Key Clinical Notes:
- Individualize dose based on age, weight, ASA status, and concurrent medications
- Resuscitation equipment and flumazenil must be immediately available
- Continuous SpO2 and blood pressure monitoring mandatory
- Status Epilepticus (Hospital Setting)
Route Dose Notes
IV (preferred) 0.1–0.2 mg/kg (max 10 mg) over 2–5 minutes May repeat once after 10–15 minutes if seizures persist
IM (if no IV access) 0.2 mg/kg (max 10 mg) single dose Preferred prehospital route per ICMR protocols
Intranasal 0.2 mg/kg (max 10 mg) — divide equally between nostrils Alternative when IV/IM not feasible
Buccal 0.3 mg/kg (max 10 mg) First-line community/prehospital option
Parameter Recommendation
Starting dose As per route above
Titration May repeat single dose after 10–15 minutes if seizure continues
Usual maintenance dose Not applicable (acute use)
Maximum dose 10 mg per dose; 20 mg cumulative before alternative agent
- Premedication Before Anaesthesia
Route Starting Dose Titration Usual Maintenance Dose Maximum Dose
Oral 7.5 mg, 30–60 minutes before procedure Not applicable 7.5–15 mg 15 mg
IV 0.02–0.04 mg/kg (1–2.5 mg), 5–10 minutes before induction Titrate in 0.5 mg increments 1–3 mg 5 mg
IM 0.07–0.1 mg/kg, 30–60 minutes before procedure Not applicable 0.07–0.1 mg/kg 0.15 mg/kg (max 10 mg)
- ICU Sedation (Mechanically Ventilated Patients)
Parameter Recommendation
Starting dose (loading) 0.03–0.1 mg/kg IV bolus over 2–3 minutes
Titration Adjust infusion rate every 15–30 minutes based on sedation scale (e.g., RASS)
Usual maintenance dose 0.03–0.1 mg/kg/hour IV continuous infusion
Maximum dose 0.2 mg/kg/hour (higher doses rarely needed; reassess if required)
Key Clinical Notes:
- Daily sedation interruption recommended to assess neurological status
- Tolerance develops with prolonged use (>5–7 days) — gradual tapering required to prevent withdrawal
- Not preferred for long-term ICU sedation — consider propofol or dexmedetomidine
Secondary Indications – Adults Only (Off-label)
- Acute Seizure Clusters (Outpatient/Prehospital Emergency) — OFF-LABEL
- Starting dose: 5–10 mg intranasally (divided between nostrils) OR 10 mg buccal
- Titration: May repeat once after 10 minutes if seizure continues
- Usual maintenance dose: Not applicable (single emergency use)
- Maximum dose: 10 mg per dose; 20 mg cumulative
- Duration: Single episode only; not for repeated daily use
- Specialist only (Neurology)
- Evidence: RAMPART trial; Indian emergency medicine protocols
- Agitation in Palliative Care — OFF-LABEL
- Starting dose: 2.5–5 mg SC/IV
- Titration: Repeat every 2–4 hours as needed
- Usual maintenance dose: 10–30 mg/24 hours via SC infusion
- Maximum dose: 60 mg/24 hours
- Duration: As per clinical need
- Specialist only (Palliative Medicine)
- Evidence: Indian palliative care protocols; international guidelines
PAEDIATRIC DOSING (Specialist Only)
Primary Indications (Approved / Standard in India)
- Acute Seizures / Status Epilepticus
Route Dose Maximum Single Dose Notes
Buccal 0.3 mg/kg 10 mg First-line prehospital per IAP guidelines
Intranasal 0.2 mg/kg (divide equally between nostrils) 10 mg Alternative if buccal not feasible
IV 0.1–0.2 mg/kg over 2–3 minutes 10 mg Hospital setting; may repeat once after 10 minutes
IM 0.2 mg/kg 10 mg If IV access unavailable
Rectal 0.3–0.5 mg/kg 10 mg Alternative route; less predictable absorption
Age-Based Buccal Dosing (Pre-filled Preparations):
Age Dose
3 months – 1 year 2.5 mg
1–5 years 5 mg
5–10 years 7.5 mg
10 years 10 mg
- Preoperative Sedation (Paediatric)
Parameter Recommendation
Starting dose (oral) 0.25–0.5 mg/kg, 20–30 minutes before procedure
Titration Not applicable
Usual maintenance dose 0.5 mg/kg
Maximum dose 20 mg
Parameter Recommendation
Starting dose (IV) 0.05–0.1 mg/kg slow bolus
Titration 0.025 mg/kg increments every 2–3 minutes
Usual maintenance dose 0.1 mg/kg
Maximum dose 0.2 mg/kg or 6 mg total
Secondary Indications – Paediatric Doses (Off-label)
- Sedation for Diagnostic Imaging (MRI/CT) — OFF-LABEL
- Starting dose (oral): 0.5 mg/kg, 20–30 minutes before procedure
- Titration: Not routinely applicable
- Usual maintenance dose: 0.5 mg/kg
- Specialist only (Paediatric Anaesthesiology/Radiology)
- Evidence: AIIMS and tertiary hospital protocols
Safety Monitoring (All Paediatric Use):
- Continuous pulse oximetry during and after administration
- Blood pressure monitoring
- Airway assessment and resuscitation equipment immediately available
- Observe for paradoxical reactions (agitation, hyperactivity)
- Monitor for respiratory depression — particularly in infants
NOT recommended below 6 months of age except under specialist supervision in ICU/anaesthesia setting. NOT recommended below 3 months for buccal/intranasal route.
- Mild to moderate impairment (eGFR 30–89 mL/min): No initial dose adjustment required; use with caution in prolonged infusions
- Severe impairment (eGFR <30 mL/min): Reduce dose by 25–50%; active metabolite (1-hydroxymidazolam glucuronide) may accumulate with prolonged use
- Haemodialysis: Not significantly removed; no supplemental dosing required; monitor for prolonged sedation
- Peritoneal dialysis: No data; use cautiously
- Mild impairment (Child-Pugh A): Initiate at lower end of dose range; slower titration recommended
- Moderate impairment (Child-Pugh B): Reduce dose by 50%; prolonged half-life expected; close monitoring required
- Severe impairment (Child-Pugh C): Avoid if possible; if essential, use minimum effective dose with intensive monitoring; risk of prolonged and profound sedation
- Known hypersensitivity to midazolam or any benzodiazepine
- Acute narrow-angle glaucoma
- Severe respiratory depression (unless mechanically ventilated)
- Acute pulmonary insufficiency
- Myasthenia gravis (risk of respiratory muscle weakness)
- Concurrent use with strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) in non-monitored settings
- Sleep apnoea syndrome (unless airway secured)
- Chronic obstructive pulmonary disease or respiratory compromise
- Elderly or debilitated patients — increased sensitivity
- Concomitant CNS depressants (opioids, alcohol, other sedatives)
- Cardiac failure with pulmonary congestion
- History of substance abuse or dependence
- Prolonged ICU use (>5–7 days) — risk of tolerance, dependence, and withdrawal
- Risk of paradoxical reactions (agitation, aggression, hostility) — more common in children, elderly, and patients with psychiatric history
Parameter Recommendation
Risk category Avoid during pregnancy, especially first and third trimesters
Preferred alternatives Lorazepam (for acute seizures); avoid all benzodiazepines if possible
When may be used Emergency seizure control when benefit clearly outweighs risk
Monitoring If used near delivery: neonatal monitoring for respiratory depression, hypotonia, poor feeding (floppy infant syndrome)
Parameter Recommendation
Compatibility Single doses generally acceptable; avoid repeated dosing
Expected drug levels in milk Low after single dose; accumulates with repeated use
Preferred alternatives Lorazepam (shorter acting, less lipophilic)
Infant monitoring Sedation, poor feeding, lethargy, respiratory depression, poor weight gain
- Starting dose: 0.5–1 mg IV for procedural sedation (50% of adult dose)
- Titration: Slower titration required; wait 3–5 minutes between increments
- Increased sensitivity to CNS depression
- Prolonged sedation and recovery
- Higher risk of respiratory depression
- Confusion, disorientation, paradoxical agitation
- Accumulation with repeated doses due to reduced hepatic clearance
Interacting Drug Effect Mechanism Management
Azole antifungals (ketoconazole, itraconazole, voriconazole) Marked increase in midazolam levels (3–5 fold) Strong CYP3A4 inhibition Avoid concurrent use; if essential, reduce midazolam dose by 50–75%
HIV protease inhibitors (ritonavir, saquinavir, lopinavir) Profound and prolonged sedation Strong CYP3A4 inhibition Contraindicated for oral midazolam; avoid parenteral if possible
Macrolide antibiotics (erythromycin, clarithromycin) Significant increase in midazolam exposure CYP3A4 inhibition Reduce midazolam dose; use azithromycin as alternative (minimal interaction)
Opioids (morphine, fentanyl, tramadol) Synergistic CNS and respiratory depression Pharmacodynamic potentiation Reduce doses of both; continuous monitoring mandatory
Alcohol Additive CNS depression; unpredictable response Pharmacodynamic interaction Avoid concurrent use
Grapefruit juice Increased oral midazolam bioavailability Intestinal CYP3A4 inhibition Avoid grapefruit juice with oral midazolam
Interacting Drug Effect Management
Rifampicin Markedly reduced midazolam efficacy Increase midazolam dose or use alternative sedative
Phenytoin, carbamazepine, phenobarbital Reduced midazolam levels CYP3A4 induction; may need higher doses
Valproate Increased sedation Displacement from protein binding; monitor sedation depth
Theophylline/aminophylline Reduced sedative effect Antagonism at GABA receptors; higher midazolam doses may be needed
Diltiazem, verapamil Modest increase in midazolam levels Moderate CYP3A4 inhibition; monitor for excess sedation
Fluconazole Moderate increase in midazolam exposure Weaker CYP3A4 inhibitor than ketoconazole; reduce dose if prolonged use
Efavirenz, nevirapine Mixed effect (induction predominates long-term) Monitor sedation; adjust dose as needed
- Drowsiness and over-sedation
- Injection site pain (IV/IM)
- Nasal irritation and discomfort (intranasal route)
- Nausea and vomiting (oral route)
- Respiratory depression/arrest: Especially with rapid IV administration, high doses, or concurrent opioid use — requires immediate airway management; flumazenil reversal available
- Hypotension: Particularly in hypovolaemic or haemodynamically unstable patients
- Bradycardia: Rare; more common with rapid IV bolus
- Paradoxical reactions: Agitation, aggression, hallucinations, involuntary movements — more common in children, elderly, psychiatric patients; may require discontinuation
- Laryngospasm/bronchospasm: Rare
- Anaphylaxis/angioedema: Very rare
- Withdrawal syndrome: After prolonged use (>7 days) — seizures, tremor, agitation; requires gradual tapering
Baseline:
- Respiratory rate and pattern
- Blood pressure and heart rate
During Procedural Sedation:
- Continuous SpO2 monitoring
- Blood pressure every 3–5 minutes
- Sedation depth assessment
ICU Infusion (>48 hours):
- Daily sedation interruption (sedation vacation)
- Liver function tests (weekly if prolonged)
- Renal function monitoring
- Assess for signs of tolerance or dependence
- Withdrawal risk assessment before discontinuation
Long-term/Repeated Use:
- Monitor for psychological dependence
- Assess cognitive function in elderly
- Mezolam (Neon Laboratories)
- Dormicum (Roche) — limited availability
- Hypnovel (Roche) — limited availability
- Versed (Abbott) — limited availability
- Injection 1 mg/mL (2 mL ampoule): ₹8–₹15
- Injection 5 mg/mL (2 mL ampoule): ₹25–₹40
- Injection 5 mg/mL (3 mL ampoule): ₹35–₹55
- Oral syrup 2 mg/mL (15 mL): ₹40–₹60
- Buccal solution (per unit dose): ₹80–₹150 (varies by strength)
- Intranasal spray device: ₹400–₹700
- Not under NPPA price control
- Available in government emergency drug kits and public hospital supplies
- Always titrate IV midazolam slowly (over 2–3 minutes) and wait adequate time between increments — peak effect takes 3–5 minutes
- Midazolam provides anxiolysis, amnesia, and sedation but has NO analgesic properties — always combine with appropriate analgesia for painful procedures
- For status epilepticus in community/prehospital settings, buccal or intranasal routes are preferred when IV access is unavailable — IM absorption is reliable and rapid
- Keep flumazenil readily available whenever using midazolam for procedural sedation — dose 0.2 mg IV, repeat every minute up to 1 mg total
- Prolonged ICU infusions (>5–7 days) require gradual tapering (reduce by 10–20% daily) to prevent withdrawal seizures and agitation
- In elderly patients, reduce doses by 50% and expect prolonged recovery — paradoxical agitation is more common in this population
midazolam; benzodiazepine; sedation; procedural sedation; status epilepticus; ICU sedation; premedication; buccal midazolam; intranasal seizure; GABA agonist
RxIndia v1.0 — 23 Mar 2025
- CDSCO approved prescribing information
- Indian Pharmacopoeia 2018
- AIIMS Anticonvulsant Protocols
- IAP Guidelines: Management of Seizures in Children
- ICMR Expert Consensus on Status Epilepticus Management
- National Neonatology Forum (NNF) Drug Manual
- Goodman & Gilman's The Pharmacological Basis of Therapeutics
- RAMPART Trial (off-label intranasal/IM use evidence)