Can Xywav (calcium, magnesium, potassium, and sodium oxybates) exacerbate liver fibrosis in a patient with hemochromatosis, potentially leading to cirrhosis?

From the Guidelines

I strongly recommend consulting with both your sleep doctor and a hepatologist to determine if Xywav should be discontinued given your liver fibrosis findings, as the current evidence suggests that patients with hemochromatosis should avoid additional liver stressors, such as certain medications, to prevent exacerbation of liver fibrosis and potential progression to cirrhosis. Xywav (calcium, magnesium, potassium, and sodium oxybates) is primarily metabolized by the liver, and while it's not commonly associated with severe liver damage, your unique situation with hemochromatosis (iron overload disorder) could potentially create a higher risk scenario 1. Hemochromatosis already causes liver stress through iron accumulation, and adding medications that require liver processing might compound this effect.

Key Considerations

• The European Association for the Study of the Liver recommends that patients with hemochromatosis should avoid iron and vitamin C supplementation, as well as heavy alcohol consumption, to reduce iron accumulation and prevent organ damage 1.
• The guidelines also suggest that patients with advanced fibrosis should be included in a screening program for hepatocellular carcinoma, and that liver biopsy can be performed to assess liver fibrosis if serum ferritin is higher than 1,000 lg/L or if liver enzymes are increased 1.
• A study published in the Journal of Hepatology found that serum ferritin is the single most important predictor of the presence of advanced hepatic fibrosis in C282Y homozygotes, and that liver biopsy does not need to be performed when ferritin is <1000 lg/L, in the absence of excess alcohol consumption and elevated serum liver enzymes 1.

Recommendations

• Continue taking your prescribed medications as stopping abruptly could worsen your narcolepsy symptoms.
• Request regular liver function monitoring and follow-up fibroscans to track any changes.
• Consider alternative narcolepsy treatments like modafinil, armodafinil, pitolisant, or solriamfetol if Xywav is discontinued.
• Lifestyle modifications, including weight management, may also be recommended as part of your comprehensive treatment plan.

From the FDA Drug Label

Patients with Hepatic Impairment The pharmacokinetics of GHB in 16 cirrhotic patients, half without ascites (Child’s Class A) and half with ascites (Child’s Class C), were compared to the kinetics in 8 subjects with normal hepatic function after a single Sodium Oxybate Oral Solution oral dose of 25 mg/kg. AUC values were double in the cirrhotic patients, with apparent oral clearance reduced from 9. 1 mL/min/kg in healthy adults to 4.5 and 4. 1 mL/min/kg in Class A and Class C patients, respectively. Elimination half-life was significantly longer in Class C and Class A patients than in control patients (mean t1/2 of 59 and 32 minutes, respectively, versus 22 minutes).

The FDA drug label does not answer the question of whether Xywav (calcium, magnesium, potassium, and sodium oxybates) can exacerbate liver fibrosis in a patient with hemochromatosis, potentially leading to cirrhosis. The label discusses the pharmacokinetics of GHB in cirrhotic patients, but does not provide information on the potential for Xywav to worsen liver fibrosis or cause cirrhosis in patients with hemochromatosis 2.

From the Research

Liver Fibrosis and Xywav

• There is no direct evidence in the provided studies to suggest that Xywav (calcium, magnesium, potassium, and sodium oxybates) exacerbates liver fibrosis in patients with hemochromatosis, potentially leading to cirrhosis 3, 4, 5, 6, 7.
• However, it is known that liver fibrosis is a sign of advanced liver disease and is often an indication for treatment 6.
• Non-invasive alternatives to biopsy, such as transient elastography and controlled attenuation parameter, are available for assessing liver fibrosis and steatosis 6, 7.

Assessment of Liver Fibrosis and Steatosis

• Transient elastography has good diagnostic accuracy compared to biopsy for the assessment of liver fibrosis and steatosis 6.
• Vibration-Controlled Transient Elastography (VCTE) with Controlled Attenuation Parameter (CAP) can be used to evaluate liver steatosis and fibrosis simultaneously 7.
• The prevalence of liver steatosis and fibrosis can be assessed using non-invasive methods, and the associated risk factors can be identified 7.

Xywav and Liver Health

• Xywav is a treatment for narcolepsy and idiopathic hypersomnia, and its long-term use has been associated with weight loss and potential health benefits due to reduced sodium content 5.
• However, there is no direct evidence to suggest that Xywav has a specific effect on liver fibrosis or steatosis in patients with hemochromatosis 3, 4, 5, 6, 7.