Midazolam Schedule (India)

Schedule H

Midazolam Routes

Oral, Intravenous (IV), Intramuscular (IM), Intranasal, Buccal, Rectal

Midazolam Formulations

Oral syrup: 2 mg/mL

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

Midazolam Adult indications

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

Midazolam Paediatric indications

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

Maximum dose: 20 mg

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.

Midazolam Renal Adjustments

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

Midazolam Hepatic adjustment

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

Midazolam Contraindications

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)

Coma (unless intubated)

Midazolam Cautions

Chronic obstructive pulmonary disease or respiratory compromise

Obstructive sleep apnoea

Elderly or debilitated patients — increased sensitivity

Concomitant CNS depressants (opioids, alcohol, other sedatives)

Cardiac failure with pulmonary congestion

History of substance abuse or dependence

Organic brain damage

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

Midazolam Pregnancy

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)

Midazolam Lactation

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

Midazolam Elderly

Starting dose: 0.5–1 mg IV for procedural sedation (50% of adult dose)

Titration: Slower titration required; wait 3–5 minutes between increments

Extra risks:

Increased sensitivity to CNS depression

Prolonged sedation and recovery

Higher risk of respiratory depression

Confusion, disorientation, paradoxical agitation

Increased fall risk

Accumulation with repeated doses due to reduced hepatic clearance

Midazolam Major drug interactions

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

Midazolam Moderate drug interactions

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

Midazolam Common Adverse effects

Drowsiness and over-sedation

Anterograde amnesia

Dizziness

Headache

Injection site pain (IV/IM)

Nasal irritation and discomfort (intranasal route)

Nausea and vomiting (oral route)

Hiccups

Fatigue

Midazolam Serious Adverse effects

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

Midazolam Monitoring requirements

Baseline:

Respiratory rate and pattern

Oxygen saturation (SpO2)

Blood pressure and heart rate

Level of consciousness

During Procedural Sedation:

Continuous SpO2 monitoring

Blood pressure every 3–5 minutes

Sedation depth assessment

Airway patency

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

Midazolam Brands in India

Mezolam (Neon Laboratories)

Midacip (Cipla)

Fulsed (Sun Pharma)

Dormicum (Roche) — limited availability

Hypnovel (Roche) — limited availability

Midazest (Zydus)

Neon Midazolam (Neon)

Versed (Abbott) — limited availability

Sedalam (Alkem)

Midazolam Price range (INR)

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

Midazolam Clinical pearls

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 Tags

midazolam; benzodiazepine; sedation; procedural sedation; status epilepticus; ICU sedation; premedication; buccal midazolam; intranasal seizure; GABA agonist

Midazolam Version

RxIndia v1.0 — 23 Mar 2025

Midazolam Reference

CDSCO approved prescribing information

Indian Pharmacopoeia 2018

API Textbook of Medicine

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)

RxIndia

The Drug Registry

Midazolam

Nitrazepam