Lorazepam

Severe respiratory insufficiency is an absolute contraindication unless mechanical ventilation support is available. Lorazepam produces dose-dependent respiratory depression that compounds pre-existing ventilatory compromise.

Sleep apnea syndrome is an absolute contraindication. GABAergic respiratory depression during sleep adds to existing apnea burden, increasing hypoxia risk.

Active substance use disorder is a relative contraindication due to lorazepam's high dependence liability and reinforcing properties confirmed in primate self-administration studies. Exception: medically supervised alcohol withdrawal detoxification, where benzodiazepines are standard of care.

While lorazepam's glucuronidation metabolism is minimally affected by liver disease, patients with hepatic encephalopathy have enhanced CNS sensitivity to GABAergic agents. Lorazepam may precipitate or worsen encephalopathy despite preserved pharmacokinetics.

Known hypersensitivity to lorazepam or any other benzodiazepine is an absolute contraindication. Cross-reactivity within the 1,4-benzodiazepine class is expected.

FDA Pregnancy Category D — evidence of fetal risk. First trimester: inconsistent data on cleft palate/lip risk, no confirmed specific malformation syndrome. Third trimester/peripartum: associated with floppy infant syndrome (neonatal hypotonia, respiratory depression, reluctance to suck) and neonatal withdrawal symptoms persisting hours to months. Lorazepam is excreted in breast milk at low levels; clinically significant infant exposure unlikely but caution warranted in premature infants.

The injectable formulation contains propylene glycol (~80% by weight) and benzyl alcohol preservative, both of which are toxic to neonates due to immature metabolic clearance. Associated with gasping syndrome and metabolic acidosis.

Lorazepam is classified as potentially inappropriate for elderly patients per the American Geriatrics Society Beers Criteria. Risks include increased cognitive impairment, excessive sedation, fall risk, and fracture. Clearance is approximately 22% lower in elderly subjects with modestly prolonged half-life.

Acute narrow-angle glaucoma is an absolute contraindication. Benzodiazepines may exacerbate intraocular pressure through mydriatic effects, risking acute glaucoma crisis.

Intra-arterial injection of the parenteral formulation is absolutely contraindicated due to risk of arterial vasospasm, thrombosis, and distal tissue necrosis.

FDA Black Box Warning: concurrent benzodiazepine-opioid use increases all-cause mortality by 75-90% and overdose death by 40-334%. Both drug classes independently suppress brainstem respiratory drive, narrowing the margin between therapeutic and lethal doses.

Intravenous lorazepam co-administered with metronidazole carries risk of a disulfiram-like reaction due to the propylene glycol vehicle in the injectable formulation. This interaction is formulation-specific and does not apply to oral lorazepam.