Ruxolitinib
Clinical safety rating: avoid
Contraindicated (not allowed)
Selective inhibitor of Janus-associated kinases (JAK) JAK1 and JAK2, reducing cytokine signaling and hematopoiesis.
| Metabolism | Hepatic metabolism primarily via CYP3A4, with minor contribution from CYP2C9. |
| Excretion | Ruxolitinib is primarily metabolized in the liver, and its metabolites are excreted renally. Approximately 74% of the dose is eliminated in urine (mainly as metabolites) and 22% in feces (as unchanged drug and metabolites). |
| Half-life | The terminal elimination half-life of ruxolitinib is approximately 3 hours for the parent drug. However, the pharmacodynamic half-life for JAK2 inhibition is longer (up to 8-12 hours) due to sustained target suppression. |
| Protein binding | Ruxolitinib is approximately 97% bound to plasma proteins, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | The volume of distribution (Vd) is approximately 72 L (about 1 L/kg), suggesting extensive tissue distribution and penetration into extravascular spaces. |
| Bioavailability | Oral bioavailability of ruxolitinib is approximately 95% after a 25 mg dose, indicating excellent absorption with minimal first-pass metabolism. |
| Onset of Action | Oral administration: Clinical effects (e.g., reduction in splenomegaly, improvement in symptoms) are typically observed within 1-2 weeks of starting therapy, with maximal response often seen by 12 weeks. |
| Duration of Action | The duration of action for symptom control is dose-dependent, with twice-daily dosing maintaining therapeutic levels. Drug levels decline rapidly after each dose, but pharmacodynamic effects persist for 8-12 hours. |
Myelofibrosis: 5-25 mg orally twice daily based on platelet count; Polycythemia Vera: 10 mg orally twice daily; Graft-versus-Host Disease: 5-10 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-59 mL/min: no adjustment; CrCl 15-29 mL/min: reduce dose by 50%; CrCl <15 mL/min or dialysis: avoid use. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Not approved for pediatric use; clinical trials for GVHD: weight-based dosing not established. |
| Geriatric use | No specific dose adjustments; monitor for thrombocytopenia and anemia more frequently due to age-related renal/hepatic decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels Can cause serious infections and myelosuppression.
| Breastfeeding | No human data on presence in breast milk. M/P ratio unknown. Based on molecular weight (306.4 Da) and protein binding (97%), excretion likely. Discontinue breastfeeding or discontinue drug, considering importance of drug to mother. |
| Teratogenic Risk | Animal studies show embryo-fetal toxicity including reduced fetal weight and skeletal variations at exposures below human therapeutic levels. No adequate human data. Risk cannot be excluded. First trimester: potential teratogen; second and third trimesters: risk of fetal myelosuppression and growth impairment. Use only if maternal benefit justifies fetal risk. |
■ FDA Black Box Warning
WARNING: Serious infections, mortality, malignancy, major adverse cardiovascular events (MACE), and thrombosis. Increased risk of serious bacterial, mycobacterial, fungal, viral infections, and opportunistic infections leading to hospitalization or death. Lymphoma and other malignancies reported. Increased rate of MACE (including cardiovascular death, MI, stroke) and thrombosis (DVT, PE) in patients with rheumatoid arthritis treated with other JAK inhibitors; risk may apply to ruxolitinib.
| Common Effects | polycythemia vera |
| Serious Effects |
["Hypersensitivity to ruxolitinib or any excipients"]
| Precautions | ["Serious infections: Evaluate and monitor for infections; interrupt therapy if serious infection occurs.","Thrombosis: Risk of DVT and PE; consider discontinuation if symptoms occur.","Malignancy: Monitor for development of malignancies, particularly lymphomas.","Cytopenias: Monitor blood counts; dose adjustments for anemia, neutropenia, thrombocytopenia.","Lipid elevation: Monitor lipids and treat hyperlipidemia.","Immunizations: Avoid live vaccines during treatment."] |
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| Fetal Monitoring | Monitor complete blood count (CBC) with differential every 2-4 weeks during pregnancy. Assess fetal growth via ultrasound every trimester. Monitor for signs of infection. Postnatal monitoring of infant for myelosuppression and infection if exposure occurred. |
| Fertility Effects | In animal studies, ruxolitinib reduced fertility in females at exposures equivalent to human therapeutic levels. No human data. Potential for reversible impairment of spermatogenesis and ovulation. Advise patients of potential impact on fertility. |