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

From the Guidelines

Xywav (calcium, magnesium, potassium, and sodium oxybates) is not directly implicated in exacerbating liver fibrosis in patients with hemochromatosis, and its use should be evaluated in the context of the patient's overall medical condition and under the guidance of a healthcare provider. The primary concern for patients with hemochromatosis is the management of iron overload, which can lead to liver fibrosis and cirrhosis 1. According to the EASL clinical practice guidelines on haemochromatosis, the focus should be on reducing iron accumulation through phlebotomy, dietary modifications, and avoiding alcohol consumption, which is a known carcinogen and can accelerate fibrosis and increase the risk of cirrhosis 1.

Key considerations for managing hemochromatosis include:

• Phlebotomy as the mainstay of therapy to reduce iron overload
• Dietary modifications to limit iron intake, such as reducing red meat consumption and avoiding iron and vitamin C supplementation
• Avoiding alcohol consumption, especially in patients with iron overload and/or liver abnormalities
• Monitoring for symptoms of liver problems and extrahepatic manifestations of the disease

In patients with hemochromatosis, liver biopsy may be considered to assess the presence of advanced fibrosis or cirrhosis, but it is not necessary for patients with serum ferritin levels <1000 lg/L in the absence of excess alcohol consumption and elevated serum liver enzymes 1. The use of Xywav in patients with hemochromatosis and liver fibrosis should be carefully evaluated, considering the potential risks and benefits, and alternative treatments for narcolepsy may be discussed with the physician based on the patient's complete medical profile.

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.