What are the side effects of lamivudine?

Side Effects of Lamivudine

Lamivudine is generally well tolerated, but common side effects include headache, nausea, malaise, fatigue, nasal symptoms, diarrhea, and cough. More serious adverse events include lactic acidosis, hepatotoxicity, and pancreatitis in pediatric patients. 1

Common Side Effects

Lamivudine has a relatively favorable side effect profile compared to many other antiviral medications. The most frequently reported adverse effects include:

• Gastrointestinal symptoms:

  • Nausea (33%)
  • Diarrhea (18%)
  • Nausea and vomiting (13%)
  • Abdominal pain (9%)
  • Abdominal cramps (6%)
  • Dyspepsia (5%)

• General symptoms:

  • Headache (35%)
  • Malaise and fatigue (27%)
  • Fever or chills (10%)

• Respiratory symptoms:

  • Nasal signs and symptoms (20%)
  • Cough (18%)

• Neurological symptoms:

  • Neuropathy (12%)
  • Insomnia and sleep disorders (11%)
  • Dizziness (10%)
  • Depressive disorders (9%)

• Skin reactions:

  • Skin rashes (9%)

• Musculoskeletal symptoms:

  • Musculoskeletal pain (12%)
  • Myalgia (8%)
  • Arthralgia (5%) 1

Serious Adverse Events

1. Lactic Acidosis and Hepatic Steatosis

Lamivudine can cause lactic acidosis and severe hepatomegaly with steatosis, which can be fatal. Signs and symptoms include:

• Severe weakness or fatigue
• Unusual muscle pain
• Difficulty breathing
• Stomach pain with nausea and vomiting
• Feeling cold (especially in arms and legs)
• Dizziness or lightheadedness
• Fast or irregular heartbeat 1

2. Hepatotoxicity

Liver problems can occur with lamivudine treatment, particularly in patients with:

• Pre-existing liver disease
• Hepatitis B or C coinfection
• Alcohol abuse

Signs of hepatotoxicity include:

• Jaundice (yellowing of skin or eyes)
• Dark or "tea-colored" urine
• Light-colored stools
• Loss of appetite
• Pain or tenderness on right side of stomach 2, 1

3. Pancreatitis in Pediatric Patients

Pancreatitis was observed in 0.3% of adult subjects in clinical trials 1. Children may be at higher risk for developing pancreatitis during treatment with lamivudine if they:

• Have taken nucleoside analogue medicines in the past
• Have a history of pancreatitis
• Have other risk factors for pancreatitis

Signs of pancreatitis include severe upper stomach pain, with or without nausea and vomiting 1.

4. Immune Reconstitution Syndrome

This occurs when the immune system begins to recover and responds to previously hidden infections in the body. Symptoms vary depending on the infection being targeted 1.

Special Considerations

Hepatitis B Patients

In patients with chronic hepatitis B, lamivudine resistance can develop with long-term use:

• Resistance rates increase from 14% in year 1 to 66% after 4 years of treatment 2
• Patients with lamivudine-resistant mutations experience significantly more hepatitis flares 3
• The occurrence of hepatic decompensation and liver-disease-related serious adverse events increases after 4 years in patients with lamivudine resistance 3

HIV Patients

When used for HIV treatment (typically at higher doses of 300mg daily), lamivudine is usually part of a combination regimen. Side effects are similar to those seen in hepatitis B treatment, but monitoring for drug interactions with other antiretrovirals is important 2.

Liver Transplant Patients

Lamivudine is used to prevent recurrence of hepatitis B after liver transplantation, often in combination with hepatitis B immune globulin (HBIG). In this population:

• Lamivudine is generally well tolerated
• Resistance development is a concern with long-term use
• Newer antivirals with lower resistance rates (entecavir, tenofovir) may be preferred for long-term use 2

Monitoring Recommendations

• Regular liver function tests
• Monitor for signs of lactic acidosis
• In pediatric patients, monitor for signs of pancreatitis
• For patients with HIV, monitor CD4 counts and viral load
• For patients with hepatitis B, monitor HBV DNA levels and resistance development

Risk Factors for Increased Side Effects

• Female gender
• Obesity
• Prolonged nucleoside exposure
• Concurrent hepatitis C infection
• Pre-existing liver disease
• Alcohol use

Conclusion

While lamivudine is generally well tolerated with primarily mild side effects, clinicians should be vigilant for the development of serious adverse events such as lactic acidosis, hepatotoxicity, and pancreatitis, particularly in high-risk populations. The development of resistance is a significant concern with long-term lamivudine therapy, especially in hepatitis B patients, and may necessitate a change in treatment strategy.