Side Effects of Actemra (Tocilizumab)
The most common and serious side effects of Actemra (tocilizumab) include serious infections, gastrointestinal perforations, liver toxicity, changes in laboratory parameters, hypersensitivity reactions including anaphylaxis, and increased risk of opportunistic infections. 1
Common Side Effects
- Upper respiratory tract infections and nasopharyngitis 1
- Headache and hypertension 1
- Elevated liver enzymes (ALT/AST) 1
- Gastrointestinal symptoms including abdominal pain and diarrhea 2
- Injection site reactions (for subcutaneous formulation) 1
Serious Side Effects
Infections
- Increased risk of serious infections including bacterial, viral, and invasive fungal infections 1
- Tuberculosis reactivation 1
- Opportunistic infections 1
- Higher infection rates compared to placebo (127 events vs 112 events per 100 patient-years) 1
- Serious infection rate of 5.3 events per 100 patient-years with 8 mg/kg dose 1
- Most common serious infections include pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis, and bacterial arthritis 1
Gastrointestinal Perforations
- Risk of tears (perforations) in the stomach or intestines 1
- Overall rate of 0.26 events per 100 patient-years 1
- Higher risk in patients taking concomitant NSAIDs, corticosteroids, or methotrexate 1
- Symptoms include fever, persistent abdominal pain, and change in bowel habits 1
Hepatotoxicity
- Risk of serious life-threatening liver problems that may require liver transplant 1
- Elevated liver enzymes requiring dose modification or discontinuation 1
- Not recommended in patients with active hepatic disease or hepatic impairment 1
- Signs include fatigue, anorexia, jaundice, abdominal swelling, and dark urine 1
Laboratory Abnormalities
- Neutropenia (decreased neutrophil count) 1
- Thrombocytopenia (decreased platelet count) 1
- Elevated lipid levels including total cholesterol, LDL, HDL, and triglycerides 1
- Abnormal liver function tests 1
Hypersensitivity Reactions
- Risk of serious allergic reactions including anaphylaxis 1, 2
- Symptoms include swelling of face/lips/mouth/tongue, breathing difficulties, skin rash, dizziness, and fast heartbeat 1
- Successful desensitization has been reported for patients with immediate hypersensitivity reactions who need to continue tocilizumab 2
Neurological Effects
- Rare cases of demyelinating disorders including multiple sclerosis and chronic inflammatory demyelinating polyneuropathy 1
- Case reports of leukoencephalopathy after long-term administration 3
Other Serious Side Effects
- Reactivation of hepatitis B in carriers 1
- Pancreatitis (rare but documented in case reports) 4
- Immunosuppression and increased risk of malignancy 1
Special Considerations
Vaccination
- Avoid live vaccines during treatment 1
- Complete all immunizations before starting therapy if possible 1
- Risk of reduced vaccine effectiveness due to IL-6 inhibition 1
Pregnancy
- May cause fetal harm; women of reproductive potential should be informed 1
Monitoring Recommendations
- Regular monitoring of neutrophil count, platelet count, and liver enzymes 1
- Lipid parameters should be assessed 4-8 weeks after initiation 1
- Monitor for signs of infection during and after treatment 1
- Watch for symptoms of gastrointestinal perforation 1
Risk Factors for Adverse Events
- Concomitant use of other immunosuppressants increases infection risk 1
- History of diverticulitis increases risk of GI perforation 1
- Pre-existing hepatic impairment increases risk of liver toxicity 1
- Higher dose (8 mg/kg) associated with greater risk of adverse events compared to lower dose (4 mg/kg) 5
Comparative Safety
- Meta-analyses show the risk of adverse events with tocilizumab is comparable to other biologics used for rheumatoid arthritis 5
- Pooled odds ratio for increased risk of adverse events with 8 mg/kg combination therapy is 1.53 (95% CI 1.26,1.86) 5
- Risk of infection is significantly higher with 8 mg/kg combination therapy compared to controls (OR = 1.30; 95% CI 1.07,1.58) 5
Understanding these side effects is crucial for proper monitoring and early intervention to minimize risks while maximizing therapeutic benefits of tocilizumab therapy.