What are the side effects of Entecavir (nucleoside analog)

Side Effects of Entecavir

Entecavir has a favorable long-term safety profile with adverse events being infrequent, though serious complications including lactic acidosis can occur, particularly in patients with severely impaired liver function. 1

Common Side Effects

The most frequently reported adverse effects of entecavir are generally mild and include:

• Headache occurs in 17-23% of patients 2
• Fatigue affects 10-13% of patients 2
• Dizziness is reported in approximately 9% of patients 2
• Nausea occurs in 6-8% of patients 2
• Upper respiratory tract infections affect 18-20% of patients 2
• Cough is seen in 12-15% of patients 2

These common side effects are similar in character, severity, and incidence to those seen with placebo or lamivudine therapy 2

Serious Adverse Effects

Lactic Acidosis

Lactic acidosis is the most serious potential complication of entecavir therapy and represents a medical emergency requiring hospitalization. 3

• Lactic acidosis risk is significantly elevated in patients with severely impaired liver function, particularly those with MELD scores ≥20 4
• In one study, 5 of 16 cirrhotic patients developed lactic acidosis, all with MELD scores ≥20, while none of the 11 patients with MELD scores <18 developed this complication 4
• Lactic acidosis occurred between 4 and 240 days after treatment initiation and was fatal in one patient 4
• The MELD score (including bilirubin, INR, and creatinine) correlated significantly with lactic acidosis development (P<0.005), while Child-Pugh score did not 4

Warning signs of lactic acidosis include: 3

• Severe weakness or fatigue
• Unusual muscle pain
• Trouble breathing
• Stomach pain with nausea and vomiting
• Feeling cold, especially in arms and legs
• Dizziness or lightheadedness
• Fast or irregular heartbeat

Hepatotoxicity

• Serious liver problems with hepatomegaly and steatosis can occur, representing a medical emergency that can cause death 3
• This risk may be higher in females, very overweight patients, or those taking nucleoside analogues long-term 3

Warning signs include: 3

• Jaundice (yellowing of skin or eyes)
• Dark urine
• Light-colored stools
• Prolonged loss of appetite
• Nausea
• Lower abdominal pain

Post-Treatment Hepatitis Exacerbation

• Severe exacerbation of hepatitis B can occur after discontinuation of entecavir, typically within 6 months of stopping treatment 3
• Patients require close monitoring with regular blood tests to check liver function if treatment is discontinued 3

Rare Adverse Effects

• Peripheral polyneuropathy has been reported in at least one case, particularly with high-dose, long-term use or in patients with pre-existing neuropathy risk factors 5

HIV-Related Considerations

• In patients with untreated HIV/HBV co-infection, entecavir may increase the risk of HIV resistance to antiretroviral medications 3
• HIV antibody testing should be performed before starting entecavir therapy 3

Resistance Development

• Entecavir has a low genotypic resistance rate of only 1.2% in nucleoside-naive patients after 5 years of treatment 1
• However, resistance rates are substantially higher (51% at 5 years) in patients with pre-existing lamivudine-resistant hepatitis B 1

Safety in Special Populations

• Dose adjustment is required in patients with creatinine clearance <50 mL/min 1
• Entecavir is not indicated if creatinine clearance is <15 mL/min without dialysis 1
• The safety profile in pregnancy is unknown; an Antiretroviral Pregnancy Registry exists for monitoring 3

Clinical Monitoring Recommendations

• Only 1% of patients discontinued entecavir therapy due to adverse events in long-term studies 1
• Regular monitoring of HBV DNA levels and liver function is essential during treatment 3
• Patients with impaired liver function (MELD ≥20) require cautious application and close monitoring for lactic acidosis 4