While dabrafenib provides precise targeted therapy for BRAF-mutant tumors, it is crucial to be aware of its potential multi-systemic adverse reactions. Clinical practice requires a balanced approach to efficacy and safety through standardized medication monitoring and individualized management strategies.
Side Effects of Dabrafenib Requiring Immediate Medical Attention
In addition to its intended effects, dabrafenib may cause several adverse reactions. While not all of these side effects will occur, if they do, medical attention may be necessary:
1. Common Side Effects: Common side effects of dabrafenib include: bleeding gums; nosebleeds; prolonged bleeding from cuts; coughing up blood; bloody, black, or tarry stools (duplicates combined); red or black tarry stools (duplicates combined); hematuria or cloudy urine; red or dark brown urine; significantly decreased urination frequency or volume; increased urination; significantly decreased urine volume; dry mouth; fruity breath; increased thirst; increased hunger; indigestion; heartburn; stomach pain or cramps; vomiting; vomiting coffee-ground-like material (severe and persistent); nausea; dizziness; headache; visual disturbances; difficulty breathing or swallowing; inability to move; tingling in the hands and feet; fever; flushed skin; dry skin; redness/swelling/painful skin; peeling skin on the hands and feet; skin blisters; rash; skin lumps or growths; skin ulcers; swelling of the feet or lower legs; unusual fatigue or weakness; unexplained weight loss; sweating.
2. Less Common Side Effects: Less common side effects of dabrafenib include blurred vision or other vision changes; color vision changes; difficulty seeing at night; eye pain; increased sensitivity of the eyes to sunlight; red eyes; and tearing pain.
3. Side Effects with Unknown Incidence: Side effects with unknown incidence of dabrafenib include blistering, peeling, or loosening of the skin; chills; cough; diarrhea; itching; joint or muscle pain; red skin lesions (usually purple in the center); sore throat; mouth or lip ulcers/white spots; swelling/pain/tenderness of the lymph nodes in the neck, armpits, or groin; and yellowing of the eyes or skin.
Side Effects of Dabrafenib Requiring Immediate Consultation with a Doctor: Some mild side effects may occur after taking dabrafenib. These reactions are usually temporary and will gradually subside as the body adapts to the drug. If symptoms persist or worsen, please contact your doctor immediately:
Acne or pimples; back pain; bloating; difficulty defecating; rapid heartbeat; hair loss or thinning hair; loose nails; loss of appetite; muscle aches/stiffness; abdominal pain (may radiate to the back); redness/pain around the nails; nasal congestion or runny nose.
Side effects of dabrafenib for medical personnel reference:
1. Cardiovascular
(1) Very common (over 10%)
Bleeding (including hemoptysis, hematoma, epistaxis, purpura, hematuria, subarachnoid hemorrhage, gastric hemorrhage, bladder hemorrhage, contusion, hematochezia, injection site bleeding, pulmonary hemorrhage, retroperitoneal hemorrhage, conjunctival hemorrhage, rectal hemorrhage, hemorrhage, melena, eye contusion, eye hemorrhage, gingival hemorrhage/bleeding, hematemesis, intracranial hemorrhage, hemorrhagic ST-swelling, hemothorax, increased tendency to bruising, colonic hemorrhage, oral bleeding, petechiae, pharyngeal hemorrhage, prolonged prothrombin time, pulmonary hematoma, retinal hemorrhage, vaginal bleeding, vitreous hemorrhage, decreased red blood cell count, postoperative bleeding, upper gastrointestinal bleeding, brainstem hemorrhage, cerebral hemorrhage; up to 29%), hypertension (including hypertensive crisis; up to 22%), bleeding events (up to 17%), hypotension (up to 15%). (2) Common (1% to 10%): Cardiomyopathy (defined as a decrease in left ventricular ejection fraction [LVEF] of at least 10% from baseline and below the institutional lower limit of normal [LLN]), decreased ejection fraction, decreased LVEF, bradycardia, lymphedema.
(3) Uncommon (0.1%-1%): Fatal hemorrhage, QT interval prolongation, left ventricular dysfunction, heart failure.
(4) Unreported frequency: Major hemorrhage (defined as symptomatic bleeding in a critical area or organ), myocarditis.
(5) Post-marketing reports: Venous thromboembolism (including pulmonary embolism, deep vein thrombosis, embolism, venous thrombosis), fatal hemorrhage in 0.5% of patients; fatal events were cerebral hemorrhage and brainstem hemorrhage.
It has been reported that in the overall safe population of this drug in combination with trametinib, 6% (65/1076) of patients experienced a decrease in LVEF; most cases were asymptomatic and reversible. Patients with LVEF below the institutional LLN were not included in the clinical trials of this drug.
2. Skin diseases
(1) Very common (10% or more)
Rash (including rashes, generalized rashes, pruritic rashes, erythematous rashes, papules, vesicular rashes, macular rashes, maculopapular rashes, folliculitis rashes, nodular rashes, pustular rashes, eczema, erythema multiforme, dermatitis, exfoliative dermatitis, skin peeling, palmoplantar erythema sensory abnormality syndrome, bullous dermatitis; up to 42%), hyperkeratosis (including hyperkeratosis, actinic keratosis, seborrheic keratosis, trichomeal keratosis; up to 42%) 37%), dry skin (including xerosis, dry dermatitis; up to 32%), hair loss (up to 26%), palmoplantar erythema hypoesthesia syndrome (up to 20%), pruritus (including pruritus, generalized pruritus, genital pruritus, ocular pruritus; up to 15%), acneiform dermatitis (including acneiform dermatitis, acne, pustular acne; up to 12%), erythema (including generalized erythema; up to 12%), palmoplantar keratosis (up to 11%), night sweats, skin effects (rash, hyperkeratosis).
(2) Common (1% to 10%) Skin effects (actinistic keratosis, skin lesions, erythema, pruritus), photosensitivity, cellulitis, folliculitis, paronychia, pustular rash, actinistic keratosis, skin lesions, hyperhidrosis, skin fissures, panniculitis.
(3) Unreported Frequency: Other serious skin toxicities, serious adverse events involving skin and subcutaneous tissue diseases, systemic exfoliative dermatitis.
(4) Post-marketing Reports: Serious skin adverse reactions (including Stevens-Johnson syndrome, eosinophilia, and systemic drug reactions), photosensitivity.
3. Gastrointestinal Reactions
(1) Very Common (10% or more): Nausea (up to 46%), vomiting (up to 37%), diarrhea (including diarrhea, colitis, enterocolitis, enteritis; up to 33%), constipation (up to 27%), abdominal pain (including abdominal pain, upper abdominal pain, lower abdominal pain; up to 16%), dry mouth (up to 11%).
(2) Common (1% to 10%): Gastrointestinal bleeding, stomatitis (including stomatitis, cheilitis, oral ulcers, aphthous ulcers, glossitis), acute pancreatitis.
(3) Uncommon (0.1%-1%): Pancreatitis, gastrointestinal perforation, colitis.
4. Genitourinary System
(1) Very Common (10% or more) Dabrafenib may cause urinary tract infections.
(2) Unreported Frequency Dabrafenib may cause uterine bleeding.
5. Hematologic System
(1) Very Common (10% or more) Leukopenia (including leukopenia, decreased white blood cell count, lymphopenia; up to 48%), neutropenia (including neutropenia, febrile neutropenia, decreased neutrophil count; up to 47%), anemia (up to 46%), decreased hemoglobin (up to 44%), lymphopenia (up to 42%).
(2) Common (1%-10%) Decreased lymphocyte count, thrombocytopenia.
(3) Unreported Frequency Neutropenia, thrombocytopenia, lymphocytosis, leukopenia.
6. Hepatotoxicity
(1) Very common (over 10%)
Elevated AST (including elevated liver enzymes, elevated liver function tests, abnormal liver function tests, hyperammemia; up to 61%), elevated ALT (including elevated liver enzymes, elevated liver function tests, abnormal liver function tests, hyperammemia; up to 48%).
(2) Common (1%-10%) Patients taking dabrafenib may experience hyperbilirubinemia and elevated GGT.
(3) Unreported frequency
Patients taking dabrafenib may experience elevated total bilirubin.
7. Hypersensitivity
(1) Common (1% to 10%) Dabrafenib may cause hypersensitivity reactions (including drug hypersensitivity).
(2) Unreported frequency
Patients taking dabrafenib may experience bullous rashes.
8. Immunological Effects
Sarcoidosis and hemophagocytic lymphohistiocytosis are also adverse reactions that may occur when taking dabrafenib.
9. Metabolism
(1) Very common (10% or more)
Hyperglycemia (up to 71%), hyponatremia (up to 57%), hypophosphatemia (up to 42%), decreased appetite (up to 29%), hypoalbuminemia (up to 25%), need for more intensive glucose-lowering therapy (up to 15%)
(2) Common (1% to 10%)
Dehydration may occur during dabrafenib treatment.
(3) Not reported frequency
Hypocalcemia, hypernatremia, hypokalemia, and elevated fasting blood glucose may also occur during dabrafenib treatment.
10. Musculoskeletal
(1) Very common (10% or more)
Arthralgia (up to 31%), myalgia (including myalgia, musculoskeletal pain, musculoskeletal chest pain; up to 24%), limb pain (up to 16%), back pain (up to 12%), muscle cramps (including muscle cramps, musculoskeletal stiffness; up to 11%).
(2) Common (1%-10%): Elevated serum creatine phosphokinase, rhabdomyolysis.
(3) Not reported frequency: Musculoskeletal pain (including back pain, myalgia, limb pain, joint pain, bone pain, non-cardiac chest pain, neck pain, musculoskeletal stiffness), jaw pain.
11. Nervous System
(1) Very common (10% or more): Headache (including headache, tension headache, migraine with aura; up to 39%), dizziness (including vertigo, vertigo, positional vertigo; up to 14%).
(2) Uncommon (0.1%-1%): Some patients may experience symptoms of intracranial hemorrhage during dabrafenib treatment.
(3) Not reported frequency: Cerebral hemorrhage, brainstem hemorrhage, peripheral neuropathy (including peripheral neuropathy, peripheral motor neuropathy, peripheral sensorimotor neuropathy, paresthesia, neuralgia, hypoesthesia, peripheral sensory neuropathy).
12. Ocular Toxicity
(1) Common (1%-10%): Uveitis, blurred vision, visual impairment, choroidal retinal disease (including choroidal retinal disorders), retinal detachment (including macular retinal pigment epithelium detachment, retinal pigment epithelium detachment), retinal pigment epithelium detachment.
(2) Uncommon (0.1%-1%): Periorbital edema may occur in some patients during dabrafenib treatment.
13. Tumors
(1) Very Common (10% or more): Skin tumors (including cutaneous skin tumors, dermatomas; up to 27%), cutaneous skin tumors (up to 24%), cutaneous squamous cell carcinoma (including cutaneous squamous cell carcinoma, squamous cell carcinoma in situ [Bowen's disease], keratoacanthoma; up to 11%).
(2) Common (1% to 10%): Keratinoma, basal cell carcinoma, newly diagnosed primary melanoma (including malignant melanoma, metastatic malignant melanoma, superficial diffuse melanoma stage III), non-cutaneous malignant tumors, acral notochord (skin tags), seborrheic keratosis, squamous cell carcinoma, and cutaneous squamous cell carcinoma.
14. Other Side Effects
(1) Very Common (10% or more): Elevated serum alkaline phosphatase (up to 64%), fever/fever (including fever, high fever, elevated body temperature; up to 63%), fatigue (including fatigue, weakness, malaise; up to 59%), weakness (up to 47%), abnormal serum phosphate (up to 42%), chills (up to 37%), decreased sodium (up to 35%), edema (including peripheral edema, edema, generalized edema; up to 35%), abnormal serum albumin (up to 25%), decreased magnesium (up to 24%), peripheral edema (including peripheral edema, peripheral swelling; up to 22%), flu-like illness (up to 15%).
(2) Common (1%-10%): Severe febrile reaction, febrile hypotension, febrile dehydration, febrile syncope, febrile renal failure, severe non-infectious febrile events, mucosal inflammation, facial edema.
(3) Unreported Frequency: Postoperative bleeding, fever with severe chills, weight gain, decreased phosphate, increased magnesium, increased potassium, decreased calcium, decreased potassium.
In the pooled safe population using this drug as a single agent, 30% of patients experienced fever (severe and non-severe); approximately 13% of these patients experienced 3 or more discrete episodes. 6% of patients experienced severe febrile reactions and fever of any severity with hypotension and chills.
15. Mental Health:
Anxiety may occur during dabrafenib treatment.
16. Nephrotoxicity:
(1) Very Common (10% or more): Increased creatinine (up to 21%) may occur during dabrafenib treatment.
(2) Common (1%-10%): Renal failure and tubulointerstitial nephritis may occur during dabrafenib treatment.
(3) Uncommon (0.1%-1%): Acute renal failure and nephritis may occur during dabrafenib treatment.
(4) Unreported Frequency
Interstitial nephritis may occur during dabrafenib treatment.
17. Respiratory System
(1) Very Common (10% or more)
Cough (including cough, expectorant cough; up to 29%), dyspnea (up to 20%), nasopharyngitis (including pharyngitis; up to 12%).
(2) Common (1%-10%)
Respiratory distress, pulmonary embolism, etc., may occur during dabrafenib treatment.
(3) Uncommon (0.1%-1%)
Pneumonia, interstitial lung disease, etc., may occur during dabrafenib treatment.
(4) Unreported Frequency
Nosebleed, upper respiratory tract infection, oropharyngeal pain, etc., may occur during dabrafenib treatment.
