Can intranasal diazepam be used in patients, particularly those with a history of seizures or acute anxiety, and what are the considerations for its use in geriatric patients or those with respiratory disease?

Can Diazepam Be Given Intranasally?

Yes, diazepam can be given intranasally, and an FDA-approved intranasal diazepam nasal spray (Valtoco®) is now available specifically for the management of acute repetitive seizures outside the hospital setting. 1, 2

FDA-Approved Intranasal Formulation

• Diazepam nasal spray is FDA-approved for acute repetitive seizures and represents a significant advancement over rectal diazepam gel, which was previously the only FDA-approved rescue medication for home use. 2
• The intranasal formulation demonstrates less pharmacokinetic variability and more reliable bioavailability compared to rectal diazepam gel, making it a superior alternative for seizure emergencies. 2
• Intranasal administration achieves peak concentration in approximately 18 minutes with a bioavailability of about 50%, and pharmacodynamic effects begin within 5 minutes. 3

Clinical Advantages of Intranasal Route

The intranasal route offers multiple practical advantages that make it particularly suitable for emergency seizure management:

• Bypasses first-pass metabolism, providing more predictable drug levels. 2
• Needle-free and painless administration, improving patient and caregiver acceptance. 2
• Can be administered by non-medical caregivers at home or in public settings, avoiding the social stigma and practical difficulties associated with rectal administration. 4, 5
• Does not require IV access, making it ideal for out-of-hospital emergencies when medical personnel are not immediately available. 6, 3

Critical Safety Monitoring Requirements

Respiratory monitoring is mandatory during intranasal diazepam administration:

• Monitor oxygen saturation and respiratory effort continuously, as there is increased risk of apnea, particularly when diazepam is given rapidly or combined with other sedative agents. 6
• Be prepared to support ventilation with respiratory assistance facilities readily available during administration. 6
• Flumazenil may reverse life-threatening respiratory depression but also counteracts anticonvulsant effects and may precipitate seizures, so use with extreme caution. 6

Special Population Considerations

For geriatric patients and those with respiratory disease:

• Use lower initial doses in older or frail patients (e.g., 2.5 mg instead of 5 mg) and titrate gradually. 7
• Exercise particular caution in patients with COPD or severe pulmonary insufficiency, as benzodiazepines can cause respiratory depression. 7
• Avoid concurrent use with other CNS depressants (benzodiazepines, opioids, skeletal muscle relaxants) outside of highly monitored settings, as this significantly increases respiratory depression risk. 7

Comparison to Other Routes for Seizures

Intranasal administration is preferred over intramuscular diazepam:

• IM diazepam is specifically NOT recommended due to erratic and unreliable absorption, risk of tissue necrosis, and availability of superior alternatives. 8
• Rectal diazepam (0.5 mg/kg up to 20 mg) provides more reliable absorption than IM administration, though absorption may still be erratic. 7, 8
• IV diazepam (0.1-0.3 mg/kg every 5-10 minutes, maximum 10 mg per dose) remains the gold standard when IV access is available, but should be administered over approximately 2 minutes to avoid pain at the IV site. 7
• Lorazepam may be preferred over diazepam when available due to prolonged duration of anticonvulsant activity, as diazepam is rapidly redistributed and seizures often recur within 15-20 minutes. 7

Contraindications and Warnings

Specific patient populations require caution or avoidance:

• Contraindicated in patients with myasthenia gravis (unless imminently dying) and severe liver disease. 7
• Tramadol reduces seizure threshold and is contraindicated in patients with a history of seizures, making benzodiazepine selection particularly important in trauma patients. 7
• Potential for paradoxical excitement or agitation, especially in younger patients. 6

Practical Administration Context

For anxiety and alcohol withdrawal (non-seizure indications):

• Diazepam is indicated for anxiety disorders and acute alcohol withdrawal symptoms (agitation, tremor, delirium tremens). 1
• Long-acting benzodiazepines like diazepam are recommended for prevention of seizures in alcohol withdrawal syndrome, with typical dosing of 5-10 mg PO/IV/IM every 6-8 hours. 7
• Lorazepam is preferred over diazepam in patients with severe AWS, advanced age, recent head trauma, liver failure, respiratory failure, or other serious medical comorbidities. 7