Fever with Melanoma Treatment: How Common It Is and How to Manage It

Fever can be a common side effect of some melanoma treatments, especially targeted therapies that combine a BRAF inhibitor with a MEK inhibitor (for example, dabrafenib plus trametinib). ^[1] In these combinations, non‑infectious fever episodes often occur within the first few months and may happen at any time during therapy. ^[2] When trametinib is given with dabrafenib, fever has been reported in over half of treated adults, with a smaller percentage experiencing more serious fever complicated by low blood pressure, chills/rigors, dehydration, or kidney issues. ^[3]

Which treatments most often cause fever?

• Targeted therapy (BRAF/MEK inhibitors): Fever is a well‑recognized, often non‑infectious side effect. It is more frequent with dabrafenib plus trametinib than with encorafenib plus binimetinib. ^[1] Patients are advised to learn early “prodrome” signs (such as chills, fatigue, dizziness) and stop the drugs promptly at symptom onset to prevent progression. ^[2]
• Immunotherapy (checkpoint inhibitors): Fever can occur but is usually less common and may signal immune‑related inflammation or, rarely, cytokine release; evaluation for infection and immune‑related events is appropriate based on symptoms. ^[4]

What does non-infectious fever look like?

Typical features include chills/rigors, dehydration, dizziness, weakness, fatigue, and sometimes hypotension, without a clear infection source. ^[2] Most events start around one month into therapy, but they can occur earlier or later, and they often resolve quickly when the medications are temporarily held. ^[2]

First steps to manage fever at home

• Temporarily stop the BRAF/MEK drugs at the first signs of fever or chills, as early interruption usually leads to rapid symptom resolution within about 24 hours. ^[2] Education to pause therapy promptly is considered an important part of safe self‑management for these regimens. ^[1]
• Use antipyretics such as acetaminophen (paracetamol) or NSAIDs to ease fever and aches, if they are safe for you. ^[5] For uncomplicated fever without localizing infection symptoms, extensive “septic work‑up” is often not required. ^[5]

When to restart your treatment

For dabrafenib plus trametinib, treatment can generally be restarted 24 hours after the fever has fully resolved. ^[5] If fever keeps coming back, your care team may adjust doses, add brief prophylaxis, or provide specific instructions for future episodes. ^[5]

When to call your care team urgently

• Fever of 38.0°C (100.4°F) or higher, persistent shaking/chills, or any signs suggesting infection (new cough, sore throat, burning with urination, redness/swelling at a wound or catheter site). ^[4] Seek help sooner if you also have low blood pressure symptoms (faintness), dehydration, or severe weakness. ^[3]

Why targeted therapies cause fever

With BRAF/MEK combinations, fever is thought to be a “pyrexia syndrome” related to treatment, not always due to infection; careful interruption and supportive care are effective. ^[6] This pattern is especially noted with dabrafenib/trametinib, where most patients’ febrile events are uncomplicated and respond quickly to brief drug holds. ^[2]

Practical tips users find helpful

• Know your early warning signs: chills, fatigue, dizziness pause the drugs and start antipyretics as directed. ^{[2] [5]}
• Hydrate and rest: dehydration can worsen symptoms, so drink fluids regularly. ^[2]
• Have a plan from your oncologist: clear instructions for pausing and restarting medication reduce ER visits and complications. ^[5]
• Report recurrent or severe episodes: dose modifications or additional strategies may be needed if fevers repeat. ^[5]

Key takeaways

Fever is common with certain melanoma targeted therapies, particularly dabrafenib plus trametinib, and can usually be managed safely by pausing treatment early and using antipyretics. ^{[1] [2]} Serious complications are uncommon but require prompt medical attention, especially if you have high temperature with low blood pressure, severe chills/rigors, dehydration, or signs of infection. ^[3] Most uncomplicated fevers resolve quickly, and treatment can often resume after 24 hours symptom‑free. ^[5]