Myelofibrosis: Ruxolitinib is indicated for the treatment of intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF in adults.

Polycythemia Vera: It is indicated for the treatment of polycythemia vera (PV) in adults who have had an inadequate response to, or are intolerant of, hydroxyurea.

Acute Graft-Versus-Host Disease: Ruxolitinib is indicated for the treatment of steroid-refractory acute graft-versus-host disease (GVHD) in adult and pediatric patients 12 years and older.

Ruxolitinib is a kinase inhibitor that selectively inhibits Janus-associated kinases JAK1 and JAK2. These kinases are involved in signaling pathways of various cytokines and growth factors essential for hematopoiesis and immune function. JAK signaling activates STAT (signal transducers and activators of transcription), which then translocates to the nucleus to regulate gene expression. Dysregulated JAK1/JAK2 signaling is a key feature of myelofibrosis. Ruxolitinib reduces splenomegaly, decreases JAK2V617F mutant cell burden in the spleen, and lowers inflammatory cytokines such as TNF-α and IL-6.

Absorption: Ruxolitinib is rapidly absorbed after oral administration, with peak plasma concentration reached within 1–2 hours. Oral bioavailability is at least 95%.

Distribution: Mean steady-state volume of distribution is about 72 L in MF and PV patients. Plasma protein binding is approximately 97%, mainly to albumin.

Metabolism: Ruxolitinib is mainly metabolized by CYP3A4 and to a lesser extent by CYP2C9 enzymes.

Excretion: After oral administration of radiolabeled ruxolitinib, about 74% of radioactivity is excreted in urine and 22% in feces. Less than 1% is excreted as unchanged drug.

Half-life: Mean elimination half-life is approximately 3–5.8 hours.

Myclofibrosis: The recommended starting dose of Ruxolitinib is based on platelet count. A complete blood count (CBC) and platelet count must be performed before initiating therapy, every 2 to 4 weeks until doses are stabilized, and then as clinically indicated. Doses may be titrated based on safety and efficacy.

• Platelet count greater than 200 × 10⁹/L: Starting dose 20 mg orally twice daily.
• Platelet count 100 × 10⁹/L to 200 × 10⁹/L: Starting dose 15 mg orally twice daily.
• Platelet count 50 × 10⁹/L to less than 100 × 10⁹/L: Starting dose 5 mg orally twice daily.

Polycythemia Vera: The recommended starting dose of Ruxolitinib is 10 mg twice daily. Doses may be titrated based on safety and efficacy. Consider decreasing the dose to 5 mg twice daily if the hemoglobin count is 8 to less than 12 g/dL and the platelet count is 50 to less than 75 × 10⁹/L.

Acute Graft-Versus-Host Disease: The recommended dose of Ruxolitinib is 5 mg twice daily. Consider increasing the dose to 10 mg twice daily after at least 3 days of treatment if the ANC and platelet counts are not decreased by 50% or more relative to the first day of dosing with ruxolitinib. Or as directed by the registered physician.

Ruxolitinib is to be taken orally, with or without food. If a dose is missed, the patient should not take an additional dose, but should take the next usual prescribed dose.

Fluconazole: Concomitant use of Ruxolitinib with fluconazole at doses greater than 200 mg daily may increase ruxolitinib exposure by inhibiting CYP3A4 and CYP2C9 pathways. Increased exposure may raise the risk of adverse reactions. The combination should be avoided when fluconazole exceeds 200 mg daily, except in patients with acute GVHD.

Strong CYP3A4 Inhibitors: Co-administration with strong CYP3A4 inhibitors increases ruxolitinib plasma levels and may enhance toxicity. Dose reduction should be considered. In acute GVHD patients, dose adjustment is recommended when used with ketoconazole, and blood counts should be monitored more frequently when used with itraconazole, adjusting dose as needed.

Strong CYP3A4 Inducers: Concomitant use may reduce ruxolitinib exposure. No routine dose adjustment is required; however, patients should be closely monitored and dose adjusted based on safety and efficacy.

Ruxolitinib is contraindicated in patients with known hypersensitivity to ruxolitinib or any of its components.

The most common adverse effects include

• thrombocytopenia, anemia, and neutropenia.
• Other effects may include increased risk of infections, bruising, dizziness, headache,
• symptom worsening after interruption or discontinuation,
• and non-melanoma skin cancer.

There are no adequate and well-controlled studies in pregnant women. It is not known whether ruxolitinib is excreted in human milk. Because many drugs are excreted in breast milk, breastfeeding should be discontinued during treatment and for 2 weeks after the final dose.

Thrombocytopenia, Anemia and Neutropenia: Ruxolitinib treatment may cause thrombocytopenia, anemia, and neutropenia. Thrombocytopenia should be managed by dose reduction or temporary interruption. Platelet transfusion may be required. Anemia may require blood transfusion and/or dose adjustment. Severe neutropenia (ANC <0.5 × 10⁹/L) is generally reversible after withholding the drug until recovery. A baseline CBC should be performed before treatment, and CBC should be monitored every 2–4 weeks until dose stabilization, then as clinically indicated.

Risk of Infection: Serious bacterial, mycobacterial, fungal, and viral infections have been reported. Treatment should be delayed until active serious infections resolve. Patients should be closely monitored for signs of infection and treated promptly.

Tuberculosis: TB infection has been reported. Patients should be evaluated for TB risk factors before starting therapy and tested for latent TB if at risk. High-risk factors include travel to endemic areas, close contact with TB patients, or history of TB. Patients with active or latent TB should be managed according to specialist advice before initiating therapy.

Progressive Multifocal Leukoencephalopathy (PML): PML has been reported. If suspected, Ruxolitinib should be discontinued and appropriate evaluation performed.

Herpes Zoster: Patients should be informed about early symptoms of shingles and advised to seek medical attention promptly if suspected.

Hepatitis B: HBV reactivation and increased viral load have been reported. Patients with chronic HBV infection should be monitored and managed according to clinical guidelines.

Symptom Exacerbation After Interruption or Discontinuation: After stopping Ruxolitinib, symptoms of myeloproliferative disorders may return within about one week. Some MF patients may develop fever, respiratory distress, hypotension, DIC, or multiorgan failure. Patients should not stop treatment without medical advice. If discontinuation is required, gradual dose tapering is recommended except in cases of thrombocytopenia or neutropenia.

Non-Melanoma Skin Cancer: Basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma have been reported. Regular skin examinations are recommended.

Lipid Elevations: Increases in total cholesterol, LDL cholesterol, and triglycerides may occur. Lipid levels should be checked 8–12 weeks after starting treatment and managed according to clinical guidelines.

Use in children: The safety and effectiveness of Ruxolitinib in pediatric patients have not been established.

There is no known specific antidote for Ruxolitinib overdose. Single doses up to 200 mg have been administered with acceptable acute tolerability. Repeated doses above the recommended range may lead to increased myelosuppression, including leukopenia, anemia, and thrombocytopenia. Appropriate supportive treatment should be provided. Hemodialysis is not expected to significantly enhance elimination of Ruxolitinib.

Pyrrolopyrimidines

Store below 30°C in a dry place, protected from sunlight. Keep out of the reach of children.