What are the side effects of Jakafi (ruxolitinib)?

Side Effects of Jakafi (Ruxolitinib)

Jakafi (ruxolitinib) commonly causes thrombocytopenia, anemia, and increased risk of infections as its primary side effects, requiring regular monitoring of blood counts and infection symptoms during treatment. 1

Common Hematologic Side Effects

• Thrombocytopenia (low platelets):

  • Main dose-limiting adverse event 1
  • May require dose adjustments or interruptions 1
  • Monitor for unusual bleeding or bruising

• Anemia (low red blood cells):

  • Especially prominent at the beginning of therapy 1
  • Due to JAK2 inhibition affecting erythropoietin signaling 2
  • May cause fatigue and shortness of breath

• Neutropenia (low neutrophils):

  • Generally reversible by withholding ruxolitinib 1
  • Increases risk of infections

Infection Risks

• Increased susceptibility to infections:

  • Bacterial, viral, fungal, and opportunistic infections 1
  • Herpes zoster (shingles) reactivation is particularly common 1
  • Tuberculosis infection has been reported 1
  • Hepatitis B viral load may increase in patients with chronic HBV 1

• Withdrawal syndrome:

  • Sudden ruxolitinib discontinuation can provoke a shock-like syndrome 1
  • Due to re-emergence of suppressed inflammatory cytokines 1
  • Abrupt interruption should be avoided; tapering is recommended 1

Metabolic and Other Side Effects

• Lipid abnormalities:

  • Increases in total cholesterol, LDL, and triglycerides 1
  • Monitor lipid parameters 8-12 weeks after starting treatment 1

• Cardiovascular risks:

  • Increased risk of major adverse cardiovascular events in patients over 50 with cardiovascular risk factors 3
  • Includes heart attack, stroke, and cardiovascular death

• Thromboembolic events:

  • Risk of venous thromboembolism (VTE) and pulmonary embolism (PE) 1
  • Higher risk with 10 mg twice daily dose compared to 5 mg twice daily 1

Monitoring Recommendations

1. Complete blood count (CBC):

   • Every 2-4 weeks until doses are stabilized 1
   • Then as clinically indicated

2. Lipid parameters:

   • 8-12 weeks after initiation 1
   • Follow clinical guidelines for hyperlipidemia management

3. Infection surveillance:

   • Assess for signs and symptoms of infections before and during treatment 1
   • Evaluate for tuberculosis risk factors 1
   • Test for latent TB in high-risk patients 1
   • Monitor for hepatitis B reactivation in patients with chronic HBV 1

Special Considerations

• Renal impairment: Dose reduction recommended for moderate to severe renal impairment 1

• Hepatic impairment: Dose reduction recommended for any degree of hepatic impairment 1

• Drug interactions: Ruxolitinib is metabolized by CYP3A4 and CYP2C9, creating potential for multiple drug interactions 4

Practical Management Tips

• Start with appropriate dosing based on platelet count 1:

  • 50-100 × 10⁹/L: 5 mg twice daily
  • 100-200 × 10⁹/L: 15 mg twice daily

  • 200 × 10⁹/L: 20 mg twice daily

• Manage cytopenias through dose modifications rather than discontinuation when possible 1

• When discontinuing, taper gradually to avoid withdrawal syndrome 1

• Consider prophylaxis for herpes zoster in high-risk patients

• Regular skin examinations are recommended due to potential increased risk of non-melanoma skin cancer 1