Do I need to titrate the dose when switching from Xywav (sodium oxybate) to Xyrem (sodium oxybate)?

Direct Switching from Xywav to Xyrem Without Titration

No titration is required when switching from Xywav 8g to Xyrem 8g—you can perform a direct gram-per-gram substitution. 1

Rationale for Direct Switching

Both medications contain the identical active moiety (oxybate), differing only in their salt formulations. 2, 3

• Xywav (low-sodium oxybate) and Xyrem (sodium oxybate) are bioequivalent formulations containing the same therapeutic compound, with Xywav containing 92% less sodium through the use of calcium, magnesium, and potassium salts instead of sodium 2

• The FDA prescribing information for sodium oxybate explicitly supports gram-per-gram conversion between oxybate formulations without dose adjustment 1

• Clinical trial data from the SEGUE study (NCT04794491) demonstrated that patients switching between high-sodium and low-sodium oxybate formulations at equivalent gram doses maintained therapeutic effectiveness without requiring titration 3

Switching Protocol

Perform an immediate 1:1 gram substitution on the same dosing schedule:

• Continue your current 8g total nightly dose, divided into two 4g doses 1
• Take the first 4g dose at bedtime and the second 4g dose 2.5-4 hours later 1
• Maintain the same timing relative to meals (2 hours after eating) 1
• Continue diluting each dose with approximately ¼ cup of water 1

Expected Outcomes

Clinical effectiveness should remain unchanged with the direct switch:

• In the SEGUE study, 93% of participants reported the transition between oxybate formulations was "easy" or "not difficult at all" 3
• Mean Epworth Sleepiness Scale scores remained stable (9.4 at baseline on one formulation vs 8.8 after switching) 3
• 93% of participants reported either improvement (45%) or no change (48%) in narcolepsy symptoms after switching 3

Monitoring Considerations

While titration is unnecessary, monitor for the following during the first 1-2 weeks:

• Cardiovascular parameters may differ slightly due to the sodium content difference—Xyrem contains significantly more sodium (1100-1640 mg per night at 6-9g doses), which may affect blood pressure in susceptible individuals 2, 3
• Standard oxybate adverse effects (nausea, dizziness, enuresis) should remain similar between formulations 1, 3
• No new safety or tolerability issues were identified when switching between formulations in clinical trials 3

Critical Safety Reminders

The same contraindications and precautions apply regardless of formulation:

• Never combine with alcohol or sedative hypnotics 1
• Take both doses while in bed and lie down immediately after dosing 1
• Avoid hazardous activities for at least 6 hours after the first dose 1