Lorazepam to Clonazepam Conversion
For an adult without severe hepatic impairment or advanced age taking lorazepam 1 mg twice daily (2 mg total daily), the equivalent clonazepam dose is 0.5 mg twice daily (1 mg total daily), using a 2:1 conversion ratio.
Conversion Ratio and Dosing
The standard benzodiazepine equivalency ratio between lorazepam and clonazepam is approximately 2:1, meaning 1 mg of lorazepam equals roughly 0.5 mg of clonazepam 1
Starting clonazepam dose: 0.5 mg twice daily (total 1 mg/day), which provides equivalent anxiolytic effect to lorazepam 2 mg/day 1
Clonazepam has a significantly longer half-life (18-50 hours) compared to lorazepam (10-20 hours), allowing for more stable plasma levels and potentially less interdose anxiety 1
Switching Strategy
Direct substitution approach: Replace lorazepam 1 mg with clonazepam 0.5 mg at each dosing time (morning and evening) without tapering, as both are intermediate-to-long acting benzodiazepines with cross-tolerance 1
Monitor for 3-5 days after the switch for any withdrawal symptoms or excessive sedation, though these are uncommon with equivalent dosing 1
If breakthrough anxiety occurs, the clonazepam dose can be increased by 0.25 mg increments rather than reverting to lorazepam 1
Pharmacokinetic Advantages in This Population
Lorazepam undergoes only hepatic glucuronidation (Phase II metabolism), making it safer in liver disease and elderly patients where oxidative metabolism is impaired 2
Clonazepam requires hepatic oxidation (Phase I metabolism) before glucuronidation, which may be problematic in patients with significant liver dysfunction 3
In adults without hepatic impairment, both medications are metabolized efficiently, but lorazepam's simpler metabolic pathway offers no particular advantage in this population 2, 4
Renal impairment does not require dose adjustment for either medication, as both parent drugs are primarily eliminated through hepatic metabolism 4, 3
Critical Monitoring Parameters
Assess for excessive sedation in the first week, as clonazepam's longer half-life may cause accumulation if the patient is particularly sensitive 1
Monitor for paradoxical agitation, which occurs in approximately 10% of patients on benzodiazepines, though this risk is similar between lorazepam and clonazepam 5
Evaluate for cognitive impairment and psychomotor slowing, particularly if the patient drives or operates machinery, as clonazepam's longer duration may cause more persistent effects 1
Screen for falls risk, especially if other CNS depressants are co-prescribed 1
Common Pitfalls to Avoid
Do not use a 1:1 conversion ratio, as this would result in significant oversedation; the 2:1 ratio (lorazepam:clonazepam) is standard 1
Avoid combining with alcohol or other CNS depressants during the transition period, as additive psychomotor impairment is more pronounced with clonazepam's longer half-life 1
Do not assume clonazepam is safer long-term—both benzodiazepines carry risks of tolerance, dependence, cognitive impairment, and should ideally be used short-term with a plan for eventual taper 5, 1
Be aware of rare hepatotoxicity: while uncommon, clonazepam has been reported to cause severe hyperlipidemia, liver dysfunction, and hyperglycemic crisis in isolated cases, particularly in patients with pre-existing metabolic abnormalities 6
Special Considerations for Hepatic Impairment
If the patient develops liver disease in the future, lorazepam would be strongly preferred over clonazepam, as lorazepam's glucuronidation pathway is minimally affected by hepatic dysfunction, whereas clonazepam's oxidative metabolism is significantly impaired 2, 3
In cirrhotic patients, clonazepam protein binding decreases (from 13.9% unbound to 17.1% unbound), potentially increasing free drug levels and toxicity risk 3