Isentress (Raltegravir) Adverse Reactions
Most Common Adverse Reactions
Raltegravir is generally well tolerated with adverse effects comparable to placebo in most studies, though specific reactions occur with notable frequency. 1
Treatment-Naïve Patients
The most common moderate-to-severe adverse reactions in treatment-naïve adults receiving raltegravir 400 mg twice daily with emtricitabine/tenofovir include: 1
- Headache: 4% (vs 5% with efavirenz)
- Insomnia: 4% (vs 4% with efavirenz)
- Nausea: 3% (vs 4% with efavirenz)
- Dizziness: 2% (vs 6% with efavirenz)
- Fatigue: 2% (vs 3% with efavirenz)
The discontinuation rate due to adverse events was 5% with raltegravir compared to 10% with efavirenz, demonstrating superior tolerability. 1
Treatment-Experienced Patients
In treatment-experienced patients, the most frequently reported adverse reactions include: 2, 3
- Diarrhea: 16.6%
- Nausea: 9.9%
- Headache: 9.7%
The discontinuation rate was only 4% in raltegravir-treated patients versus 5% with placebo. 1
Serious Adverse Reactions
Skin and Hypersensitivity Reactions
Serious skin reactions and allergic reactions can be severe, life-threatening, or fatal. 1 Patients should stop raltegravir immediately and contact their physician if they develop: 1
- Rash with fever, general malaise, or extreme tiredness
- Muscle or joint aches
- Blisters or sores in mouth
- Blisters or peeling of skin
- Redness or swelling of eyes
- Swelling of mouth or face
- Difficulty breathing
Few hypersensitivity reactions have been reported with raltegravir compared to other antiretroviral classes, suggesting this class may be safer from this perspective. 4
Hepatotoxicity
Allergic reactions can affect body organs including the liver. 1 Signs of liver problems requiring immediate medical attention include: 1
- Yellowing of skin or whites of eyes
- Dark or tea-colored urine
- Pale-colored stools
- Nausea or vomiting
- Loss of appetite
- Right-sided abdominal pain, aching, or tenderness
Muscle Disorders
Myopathy and rhabdomyolysis have been reported with raltegravir. 1, 5 Patients should report unexplained muscle pain, tenderness, or weakness immediately, as these may indicate a rare serious muscle problem that can lead to kidney problems. 1
Immune Reconstitution Syndrome
Immune reconstitution inflammatory syndrome can occur when starting HIV medications, as the immune system strengthens and begins fighting previously hidden infections. 1 Patients should report any new symptoms after starting raltegravir. 1
Laboratory Abnormalities
Hematologic Changes
Grade 2-4 laboratory abnormalities in treatment-naïve patients include: 1
- Absolute neutrophil count (Grade 2-4): 7% with raltegravir vs 7% with efavirenz
- Hemoglobin (Grade 2-4): 2% with raltegravir vs 2% with efavirenz
- Platelet count (Grade 2-4): 1% with raltegravir vs <1% with efavirenz
Hepatic Enzyme Elevations
Mild elevations in liver transaminases have been reported. 3 In treatment-naïve patients: 1
- AST elevation (Grade 2-4): 14% with raltegravir vs 13% with efavirenz
- ALT elevation (Grade 2-4): 15% with raltegravir vs 15% with efavirenz
Creatine Kinase Elevations
Grade 2-4 creatine kinase laboratory abnormalities were observed in subjects treated with raltegravir. 1 In treatment-experienced patients: 1
- Grade 2 (6.0-9.9 × ULN): 2%
- Grade 3 (10.0-19.9 × ULN): 4%
- Grade 4 (≥20.0 × ULN): 3%
Lipid Changes
Raltegravir demonstrates favorable lipid profiles compared to efavirenz. 1 Mean changes from baseline at Week 240 in treatment-naïve patients showed: 1
- LDL cholesterol: +10 mg/dL (raltegravir) vs +25 mg/dL (efavirenz)
- Total cholesterol: +16 mg/dL (raltegravir) vs +44 mg/dL (efavirenz)
- Triglycerides: +2 mg/dL (raltegravir) vs +37 mg/dL (efavirenz)
Less Common Adverse Reactions
Additional adverse reactions occurring in <2% of patients but included due to seriousness or potential causal relationship include: 1
- Abdominal pain, gastritis, dyspepsia, vomiting
- Asthenia
- Hepatitis
- Genital herpes, herpes zoster
- Depression (particularly in patients with pre-existing psychiatric illness), including suicidal ideation and behaviors
- Nephrolithiasis, renal failure
Comparative Safety Profile
Among integrase inhibitors, raltegravir has the longest safety record and fewest drug interactions. 4 The 2018 International Antiviral Society-USA Panel noted that raltegravir was superior to ritonavir-boosted atazanavir and ritonavir-boosted darunavir in comparative clinical trials. 4
Concerns regarding neural tube defects in infants born to women who conceived while taking dolutegravir remain unknown as to whether this is a class effect that applies to raltegravir. 4
Key Clinical Considerations
Raltegravir does not cause the metabolic complications, neuropsychiatric symptoms, or significant lipid abnormalities associated with other antiretroviral classes. 4, 5 It is not a CYP450 substrate, inducer, or inhibitor, resulting in minimal drug-drug interactions. 2
The most important pitfall to avoid is failing to recognize early signs of serious skin reactions or muscle toxicity, both of which require immediate drug discontinuation and medical evaluation. 1