What to do with a patient on Sofosbuvir (sofosbuvir) and Velpatasvir (velpatasvir) for Hepatitis C Virus (HCV) treatment with Chronic Kidney Disease (CKD) stage 5 on Maintenance Hemodialysis (MHD) presenting with abdominal pain and vomiting?

Management of Abdominal Pain and Vomiting in CKD-5 Hemodialysis Patient on Sofosbuvir/Velpatasvir

Do not discontinue the sofosbuvir/velpatasvir therapy based solely on gastrointestinal symptoms, as this regimen is safe and effective in ESRD patients on hemodialysis, but immediately evaluate for alternative causes of abdominal pain and vomiting that are common in this population.

Immediate Clinical Assessment

Evaluate for serious complications unrelated to HCV therapy:

• Rule out dialysis-related complications: Assess for peritonitis (if on peritoneal dialysis), vascular access infection, or dialysis disequilibrium syndrome 1
• Assess for uremia-related symptoms: Check recent dialysis adequacy (Kt/V), as inadequate dialysis can cause nausea and vomiting independent of medication effects 1
• Exclude acute abdominal emergencies: Mesenteric ischemia, bowel obstruction, or perforation are critical diagnoses that require urgent surgical evaluation 1
• Check for electrolyte disturbances: Hyperkalemia, hypercalcemia, or severe metabolic acidosis can present with gastrointestinal symptoms in dialysis patients 1

Safety Profile of Sofosbuvir/Velpatasvir in This Population

The regimen is well-tolerated with minimal gastrointestinal toxicity:

• Nausea and vomiting occur in only 14% of ESRD patients on sofosbuvir/velpatasvir, making it an uncommon but recognized side effect 1
• No patients discontinued therapy due to adverse events in the pivotal phase II trial of 59 ESRD patients on dialysis 1
• Headache (17%) and fatigue (14%) are more common than gastrointestinal symptoms in this population 1
• All serious adverse events in clinical trials were deemed unrelated to sofosbuvir/velpatasvir, with 96-100% achieving sustained virological response 1, 2, 3

Renal Safety Considerations

Sofosbuvir accumulation does not cause clinically significant renal deterioration:

• GS-331007 (sofosbuvir metabolite) accumulates 20-fold in hemodialysis patients, but this has not translated to increased toxicity in clinical practice 4, 5, 6
• Recent evidence confirms safety: Multiple studies demonstrate no significant renal impact, with creatinine returning to baseline levels after treatment in patients with eGFR <30 mL/min 6, 7
• The 2020 EASL guidelines state that sofosbuvir/velpatasvir is safe in hemodialysis patients despite earlier concerns about metabolite accumulation 4

Differential Diagnosis for Symptoms

Consider these common causes in ESRD patients:

• Medication-related: Review all concurrent medications, particularly phosphate binders, iron supplements, or antibiotics that commonly cause gastrointestinal upset 1
• Gastroparesis: Common in dialysis patients, especially those with diabetes, causing nausea and vomiting 1
• Peptic ulcer disease: ESRD patients have increased risk; consider proton pump inhibitor therapy if not already prescribed 8
• Viral gastroenteritis or food-borne illness: Obtain stool studies if diarrhea is present 1

Management Algorithm

Follow this stepwise approach:

1. Continue sofosbuvir/velpatasvir unless severe symptoms develop requiring hospitalization 1, 2, 3
2. Provide symptomatic treatment: Antiemetics (ondansetron 4-8 mg as needed), proton pump inhibitors (pantoprazole 40 mg daily requires no dose adjustment in ESRD), and ensure adequate hydration during dialysis 8
3. Monitor closely: Check complete blood count, comprehensive metabolic panel, and assess dialysis adequacy 1
4. Reassess in 48-72 hours: If symptoms persist or worsen despite symptomatic treatment, consider imaging (abdominal ultrasound or CT) to exclude structural pathology 1
5. Complete the full 12-week course: The high SVR12 rate of 95-96% justifies continuing therapy through mild-to-moderate gastrointestinal symptoms 1, 2, 3

When to Consider Discontinuation

Only discontinue if:

• Severe, intractable vomiting leading to inability to take oral medications or maintain adequate nutrition 1
• Development of serious adverse events such as hepatic decompensation, though this is extremely rare 1
• Confirmed alternative diagnosis requiring treatment that contraindicates continuation (e.g., acute pancreatitis, bowel obstruction) 1

Critical Pitfalls to Avoid

• Do not assume gastrointestinal symptoms are drug-related without excluding other common causes in ESRD patients 1
• Do not reduce sofosbuvir dose: Full-dose therapy (400 mg/100 mg) is required for efficacy, and dose reduction is not recommended even in ESRD 4, 5, 1
• Do not add ribavirin to manage symptoms, as it significantly increases anemia risk and requires substantial hematopoietic support in ESRD 4, 7
• Do not delay dialysis sessions thinking it will improve drug tolerance; maintaining adequate dialysis is essential 1