ruxolitinib

REMS

Intermediate or high-risk myelofibrosis (including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocytopenia fibrosis).
Polycythemia vera in patients who have had an inadequate response to or are intolerant of hydroxyurea
Steroid-refractory acute graft-versus-host disease (GVHD).

Contraindicated in:

End-stage renal disease (CCr <15 mL/min) not requiring dialysis;
Concurrent use of fluconazole at doses >200 mg/day (for myelofibrosis and polycythemia vera);
Lactation: Lactation.

Use Cautiously in:

Hepatic/moderate renal impairment (dose ↓ recommended);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children.

Drug-drug:

Concurrent use of strong inhibitors of the CYP3A4 enzyme system including clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole. lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, and voriconazole may ↑ blood levels and effects; initial dose may need to be ↓ (depends on indication).
Fluconazole (a combined CYP3A4 and CYP2C9 inhibitor) may ↑ blood levels and effects; initial dose should be ↓; avoid concomitant use of fluconazole doses >200 mg/day in patients with myelofibrosis or polycythemia vera.

Natural-Food Products:

Concurrent use with grapefruit juice may ↑ levels and effects; initial dose should be ↓.

Tablets: 5 mg; 10 mg; 15 mg; 20 mg; 25 mg

Myelofibrosis

PO (Adults ): Platelet count >200 × 10⁹/L—20 mg twice daily initially, ↑ dose based on response to a maximum of 25 mg twice daily; Platelet count between 100 × 10⁹/L and 200 × 10⁹/L—15 mg twice daily initially; ↑ dose based on response to a maximum of 25 mg twice daily; Platelet count between 50 × 10⁹/L and 99 × 10⁹/L—5 mg twice daily initially; ↑ dose based on response to a maximum of 25 mg twice daily; Concurrent use of strong CYP3A4 inhibitors or fluconazole (≤200 mg/day) and platelet count ≥ 100 × 10⁹/L—10 mg twice daily initially; ↑ dose based on safety and efficacy; Concurrent use of strong CYP3A4 inhibitors or fluconazole (≤200 mg/day) and platelet count 50–100 × 10⁹/L—5 mg once daily initially; ↑ dose based on safety and efficacy; Concurrent use of strong CYP3A4 inhibitors or fluconazole (≤200 mg/day) and already on stable dose of ≥10 mg twice daily—↓ dose by 50%; ↑ dose based on safety and efficacy; Concurrent use of strong CYP3A4 inhibitors or fluconazole (≤200 mg/day) and already on stable dose of 5 mg twice daily—↓ dose to 5 mg once daily; ↑ dose based on safety and efficacy; Concurrent use of strong CYP3A4 inhibitors or fluconazole (≤200 mg/day) and already on stable dose of 5 mg once daily—Avoid concomitant use.

Hepatic Impairment

PO (Adults ): Mild, moderate, or severe hepatic impairment with platelet count between 100 × 10⁹/L and 150 × 10⁹/L—10 mg twice daily initially.

Renal Impairment

PO (Adults ): CCr 15–59 mL/min and platelet count between 100 × 10⁹/L and 150 × 10⁹/L—10 mg twice daily initially; CCr 15–59 mL/min and platelet count <100 × 10⁹/L—Avoid; CCr <15 mL/min (not on dialysis)—Avoid; CCr <15 mL/min (on dialysis) and platelet count between 100 × 10⁹/L and 200 × 10⁹/L——15 mg after dialysis; CCr <15 mL/min (on dialysis) and platelet count between >200 × 10⁹/L —20 mg after dialysis.

Polycythemia Vera

PO (Adults ): 10 mg twice daily, ↑ dose based on response to a maximum of 25 mg twice daily; Concurrent use of strong CYP3A4 inhibitors or fluconazole (≤200 mg/day)—5 mg twice daily initially; ↑ dose based on safety and efficacy; Concurrent use of strong CYP3A4 inhibitors or fluconazole (≤200 mg/day) and already on stable dose of ≥10 mg twice daily—↓ dose by 50%; ↑ dose based on safety and efficacy; Concurrent use of strong CYP3A4 inhibitors or fluconazole (≤200 mg/day) and already on stable dose of 5 mg twice daily—↓ to 5 mg once daily; ↑ dose based on safety and efficacy; Concurrent use of strong CYP3A4 inhibitors or fluconazole (≤200 mg/day) and already on stable dose of 5 mg once daily—Avoid concomitant use.

Hepatic Impairment

PO (Adults ): Mild, moderate, or severe hepatic impairment—5 mg twice daily initially.

Renal Impairment

PO (Adults ): CCr 15–59 mL/min—5 mg twice daily initially; CCr <15 mL/min (not on dialysis)—Avoid; CCr <15 mL/min (on dialysis)——10 mg after dialysis.

Acute GVHD

PO (Adults and Children ≥12 yr): 5 mg twice daily initially; ↑ dose to 10 mg twice daily after ≥3 days of treatment if ANC and platelet counts are not ↓ by ≥50% (compared to baseline). Concurrent use of ketoconazole—5 mg once daily initially; ↑ dose based on safety and efficacy.

Hepatic Impairment

PO (Adults and Children ≥12 yr): Stage 3 or 4 liver GVHD—Monitor blood counts more frequently for toxicity; consider adjustment to 5 mg once daily.

Renal Impairment

PO (Adults and Children ≥12 yr): CCr 15–59 mL/min—5 mg twice daily initially; CCr <15 mL/min (on dialysis)—5 mg after dialysis

Inhibits kinases involved in the signaling of hematopoiesis and immune processes.

Therapeutic effects:

Decreased spleen size.
Hematocrit control.
Reduction in organ involvement.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Absorption: Well absorbed (95%) following oral administration.

Distribution: Unknown.

Protein Binding: 97%.

Metabolism/Excretion: Mostly metabolized (99%) the liver (CYP3A4 enzyme system). Some metabolites have pharmacologic activity and account for 18% of action. Metabolites are excreted in urine (74%) and feces (22%).

Half-Life: Ruxolitinib—3 hr; Ruxolitinib plus metabolites—5.8 hr.

(blood levels)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–2 hr	12 hr

Instruct patient to take ruxolitinib as directed. If a dose is missed, omit and take next dose at prescribed time; do not double doses. When discontinuing therapy, unless for thrombocytopenia, decrease gradually by 5 mg twice daily each wk. If therapy is discontinued, signs and symptoms of myelofibrosis are expected to return.
Instruct patient to avoid drinking grapefruit juice during therapy; may affect blood levels of ruxolitinib.
Advise patient to notify health care professional promptly if signs and symptoms of infections, PML (progressive weakness on one side of the body or clumsiness of limbs; disturbance of vision; changes in thinking, memory, and orientation leading to confusion and personality changes), or herpes zoster occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during and for 2 wk after final dose of therapy.
Inform patient of the need for frequent blood test to monitor for adverse reactions.

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Indications ⬇

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