Anquil

Approved Indications:

• Procedural sedation: For diagnostic or therapeutic procedures (e.g., endoscopy, minor surgery) in adults and children.
• Induction and maintenance of anesthesia: As part of balanced anesthesia or for general anesthesia induction.
• Sedation in intensive care units (ICU): For mechanically ventilated patients via continuous IV infusion.
• Acute seizure management: Including status epilepticus via IM, IV, intranasal, buccal, or rectal administration.
• Premedication before surgery or diagnostic procedures: To reduce anxiety and facilitate anesthesia induction.

Off-Label/Clinically Accepted Uses:

• Palliative sedation: For terminally ill patients experiencing distress.
• Anxiolysis in minor outpatient procedures: Including dental sedation.
• Insomnia (short-term use) in specific hospitalized patients under strict supervision.

Dosage must be individualized based on patient factors, clinical condition, and desired depth of sedation.

Routes: IV, IM, oral, intranasal, buccal, rectal

Adults:

• IV sedation for procedures:
  1–2.5 mg slow IV push (over ≥2 minutes); may titrate in 0.5–1 mg increments every 2–3 minutes to effect.
  Max total: ~5 mg.
• Anesthesia induction:
  0.1–0.3 mg/kg IV over 20–30 seconds; onset in 1–2 minutes.
• ICU sedation (IV infusion):
  Initial bolus: 0.01–0.05 mg/kg, then infusion: 0.02–0.1 mg/kg/hr.
• IM premedication:
  0.07–0.1 mg/kg (approx. 5 mg) 30–60 minutes before surgery.
• Intranasal for seizures:
  5 mg (one nostril) in adults and children >40 kg.

Pediatric Dosage:

• Oral premedication: 0.25–1 mg/kg (max 20 mg), given 30 minutes before procedure.
• IV sedation: 0.05–0.1 mg/kg (slow IV push); titrate to effect.
• Intranasal or buccal for seizures: 0.2 mg/kg (max 10 mg); may repeat once.

Special Populations:

• Elderly or debilitated patients: Start at lower IV doses (e.g., 0.5 mg), titrate slowly.
• Renal impairment: Monitor for prolonged sedation due to active metabolites.
• Hepatic impairment: Reduce dose; risk of accumulation and prolonged effects.

Midazolam is a short-acting benzodiazepine that enhances the effect of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the CNS. It binds to a specific site on the GABAA receptor complex, increasing the frequency of chloride channel opening. This leads to neuronal hyperpolarization, reducing excitability and producing sedative, anxiolytic, hypnotic, amnestic, anticonvulsant, and muscle relaxant effects.

• Absorption:
  • Oral bioavailability ~40–50%.
  • Intranasal ~44–83%.
  • IM ~90–100%.
• Distribution:
  • Rapid onset of action (IV: 1–5 minutes).
  • Volume of distribution: 0.7–1.2 L/kg.
  • Plasma protein binding: ~94–97%.
• Metabolism:
  • Primarily hepatic via CYP3A4 to active metabolite 1-hydroxymidazolam.
• Elimination:
  • Metabolites excreted in urine.
  • Elimination half-life: 1.5–2.5 hours in healthy adults; prolonged in elderly or liver disease.

• Pregnancy:
  • FDA Pregnancy Category D.
  • Use only if potential benefits justify potential risks. Avoid use during labor and delivery due to neonatal CNS/respiratory depression risk.
• Lactation:
  • Excreted in breast milk in small amounts.
  • Generally considered safe with single doses; avoid repeated high doses. Monitor infant for sedation or feeding difficulties.

• Primary Class: Benzodiazepine
• Subclass: Short-acting benzodiazepine (imidazobenzodiazepine derivative)
• Therapeutic Use: Sedative, anxiolytic, anticonvulsant, and anesthetic adjunct

• Hypersensitivity to midazolam or other benzodiazepines
• Acute narrow-angle glaucoma
• Severe respiratory insufficiency (unless mechanically ventilated)
• Concurrent use with potent CYP3A4 inhibitors without dose adjustment
• Use as a sole agent for major surgical anesthesia

• Respiratory depression and arrest: Particularly with IV use or when combined with other CNS depressants; requires close monitoring.
• Hypotension and bradycardia: May occur, especially with rapid IV administration.
• Paradoxical reactions: Agitation, hallucinations, and aggression may occur, especially in pediatric or elderly patients.
• Prolonged sedation: May occur in renal/hepatic impairment due to active metabolite accumulation.
• Dependence and withdrawal: Risk increases with long-term or high-dose use.
• Black box warning: Use with opioids may result in profound sedation, respiratory depression, coma, or death.

Common:

• Drowsiness, sedation
• Amnesia (anterograde)
• Dizziness, ataxia
• Nausea, vomiting

Serious:

• Respiratory depression, apnea
• Hypotension, cardiac arrhythmias
• Paradoxical excitation
• Anaphylaxis or hypersensitivity reactions
• Withdrawal symptoms: agitation, tremors, seizures (on abrupt discontinuation)

Onset: Typically within 1–5 minutes IV; 15–30 minutes IM or oral
Severity: Dose-dependent; most effects are transient with appropriate monitoring

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin, ritonavir):
  ↑ Midazolam levels → prolonged sedation, respiratory depression
• CYP3A4 inducers (e.g., rifampin, carbamazepine):
  ↓ Efficacy of midazolam
• CNS depressants (e.g., opioids, alcohol, antipsychotics, antihistamines):
  Additive CNS and respiratory depression
• Grapefruit juice: May increase plasma concentrations

• Intranasal midazolam has been added to emergency treatment guidelines for acute seizure clusters in children and adults.
• ICU sedation protocols favor intermittent boluses or low-dose infusions over prolonged infusions to reduce delirium risk.
• FDA warning (updated): Caution on concurrent opioid use due to risk of respiratory depression and death.

• Ampoules/Vials:
  Store at 20°C to 25°C (68°F to 77°F); protect from light. Do not freeze.
• Oral syrup/solution:
  Store between 15°C and 30°C. Follow manufacturer’s instructions for specific refrigeration needs. Protect from moisture.
• Intranasal/buccal formulations:
  Keep tightly closed and protected from heat and direct light.