What is the alprazolam (Xanax) to diazepam (Valium) dose conversion ratio and how should I safely switch a patient, particularly in older adults or those with hepatic impairment?

Alprazolam to Diazepam Dose Conversion

Standard Conversion Ratio

The alprazolam to diazepam conversion ratio is approximately 1:10 to 1:14, meaning 1 mg of alprazolam is roughly equivalent to 10-14 mg of diazepam. 1

• A 1:10 ratio (1 mg alprazolam = 10 mg diazepam) is the most commonly cited equivalency for hypnosedative and anxiolytic properties in clinical practice. 1
• Some evidence suggests a 1:14 ratio may be more appropriate to account for alprazolam's higher reinforcing properties and abuse potential. 1
• For practical switching purposes, use the 1:10 ratio as your starting point, then titrate based on clinical response. 1

Switching Protocol: General Adult Population

When converting from alprazolam to diazepam, calculate the equivalent diazepam dose using the 1:10 ratio, then reduce by 20-30% to account for incomplete cross-tolerance.

Step-by-Step Conversion:

• Calculate the total daily alprazolam dose (e.g., 2 mg alprazolam daily). 2
• Multiply by 10 to get the theoretical diazepam equivalent (e.g., 2 mg × 10 = 20 mg diazepam daily). 1
• Reduce the calculated dose by 20-30% to prevent oversedation during the switch (e.g., 20 mg × 0.75 = 15 mg diazepam daily). 3
• Divide the total daily diazepam dose into 2-3 administrations to maintain steady plasma levels. 2
• Monitor closely for 3-5 days before making further adjustments, as diazepam has a longer half-life (20-100 hours including active metabolites) compared to alprazolam (9-16 hours). 2, 4

Special Populations: Elderly Patients

Elderly patients require significantly lower starting doses—begin with 0.25 mg alprazolam two to three times daily, or when switching to diazepam, use 2.5 mg two to three times daily (equivalent to 5-7.5 mg total daily). 5

Critical Adjustments for Older Adults:

• Alprazolam clearance is reduced in many elderly individuals, even those who appear healthy, leading to drug accumulation. 2
• Start at the lowest possible dose (0.25 mg alprazolam or 2.5 mg diazepam) to reduce risk of excessive sedation, falls, cognitive impairment, and respiratory depression. 5
• Avoid rapid dose escalation—allow at least 3-4 days between titration steps to assess full pharmacodynamic effects. 5
• Diazepam oxidative metabolism is particularly impaired in the elderly, making accumulation more likely than with alprazolam. 6
• If adverse effects occur at the recommended low starting dose, further reduce the dose rather than discontinuing therapy abruptly. 5

Special Populations: Hepatic Impairment

In patients with liver disease, lorazepam or oxazepam are safer alternatives than either alprazolam or diazepam, but if you must use diazepam, reduce the dose by at least 50% and monitor intensively. 6

Hepatic Impairment Considerations:

• Alprazolam clearance is significantly reduced in cirrhosis, leading to prolonged half-life and accumulation. 2
• Diazepam undergoes hepatic oxidation before glucuronidation, and oxidation is markedly impaired in liver disease, causing excessive sedation and respiratory depression. 7, 6
• The dose of diazepam required in chronic liver disease is approximately 35% lower than in healthy controls (17.9 mg vs 27 mg to achieve similar clinical effects). 7
• Lorazepam undergoes only glucuronidation (not oxidation), making it the safest benzodiazepine choice in hepatic impairment, as glucuronidation is minimally affected by liver disease. 6
• If switching from alprazolam to diazepam in hepatic impairment is unavoidable, use a 1:10 conversion ratio, then reduce by 50% (not just 20-30%), and divide into smaller, more frequent doses. 7, 6

Special Populations: Renal Impairment

Renal disease causes reduced plasma protein binding of alprazolam (increased free fraction) and may reduce free clearance, requiring dose reduction. 2

• Monitor for increased sedation due to higher free drug concentrations in plasma. 2
• Diazepam and its active metabolites also accumulate in renal impairment, though to a lesser extent than with oxidative metabolism impairment. 6
• Consider lorazepam as a safer alternative in combined renal and hepatic impairment. 6

Common Pitfalls to Avoid

Do not apply standard adult dosing to elderly or hepatically impaired patients—this is the most common and dangerous error in benzodiazepine switching. 5, 6

Critical Errors to Prevent:

• Never use a 1:1 or 1:5 ratio—this will result in severe oversedation, as alprazolam is significantly more potent than diazepam. 1
• Do not switch abruptly without overlap—consider a brief period (2-3 days) of partial overlap to prevent withdrawal symptoms. 2
• Avoid using diazepam in elderly or hepatically impaired patients when lorazepam or oxazepam are available, as these undergo only glucuronidation and are much safer. 6
• Do not forget to account for diazepam's long half-life and active metabolites—effects accumulate over 5-7 days, so initial tolerance does not predict steady-state response. 2, 6
• Never escalate doses within the first 3-4 days of switching, as peak effects may not yet be apparent. 5
• Alprazolam has higher reinforcing properties and abuse potential than diazepam, so patients may report subjective preference for alprazolam even when diazepam provides equivalent anxiolysis. 1

Drug Interactions Requiring Dose Adjustment

Coadministration of cimetidine, fluoxetine, fluvoxamine, or propoxyphene significantly impairs alprazolam clearance and requires dose reduction. 2

• These inhibitors can increase alprazolam plasma concentrations by 30-50%, necessitating proportional dose reductions. 2
• Diazepam metabolism is similarly affected by CYP450 inhibitors, so the same precautions apply after switching. 6
• Propranolol, metronidazole, disulfiram, oral contraceptives, and ethanol do not significantly alter alprazolam pharmacokinetics. 2