Ruxolitinib (systemic): Drug information

For additional information see "Ruxolitinib (systemic): Patient drug information" and "Ruxolitinib (systemic): Pediatric drug information"

For abbreviations, symbols, and age group definitions show table

Brand Names: US

Jakafi

Brand Names: Canada

Jakavi

Pharmacologic Category

Antineoplastic Agent, Janus Associated Kinase Inhibitor;
Antineoplastic Agent, Tyrosine Kinase Inhibitor;
Janus Associated Kinase Inhibitor;
Janus Kinase Inhibitor

Dosing: Adult

Dosage guidance:

Safety: Delay initiating ruxolitinib until after active infections have resolved.

Dosing: If discontinuing ruxolitinib for reasons other than thrombocytopenia, consider gradually tapering off (by 5 mg twice daily each week).

Clinical considerations: If appropriate, utilize prophylactic antibiotics according to clinical practice guidelines.

Graft-versus-host disease, acute, steroid refractory, treatment

Graft-versus-host disease, acute, steroid refractory, treatment: Oral: Initial: 5 mg twice daily. Consider increasing the dose to 10 mg twice daily after at least 3 days of treatment (if ANC and platelets are not decreased by ≥50% compared to baseline [first day of ruxolitinib]).

Consider tapering ruxolitinib after 6 months of therapy if response occurs and therapeutic corticosteroid doses have been discontinued; taper by one dose level approximately every 8 weeks (10 mg twice daily to 5 mg twice daily to 5 mg once daily). Consider retreatment if acute graft-versus-host disease (GVHD) signs/symptoms recur during or after tapering ruxolitinib.

Off-label dosing: Oral: Initial: 10 mg twice daily (may continue calcineurin inhibitor and glucocorticoid therapy with ruxolitinib); in patients who respond, may begin tapering off after 56 days (Ref). Refer to protocol for dosage adjustment and tapering recommendations.

Graft-versus-host disease, chronic, refractory, treatment

Graft-versus-host disease, chronic, refractory, treatment: Oral: Initial: 10 mg twice daily (Ref).

Consider tapering ruxolitinib after 6 months of therapy if response occurs and therapeutic corticosteroid doses have been discontinued; taper by one dose level approximately every 8 weeks (10 mg twice daily to 5 mg twice daily to 5 mg once daily). Consider retreatment if chronic GVHD signs/symptoms recur during or after tapering ruxolitinib.

Myelofibrosis

Myelofibrosis: Initial dose (based on platelet count, titrate dose thereafter based on efficacy and safety):

Platelets >200,000/mm³: Oral: 20 mg twice daily

Platelets 100,000 to 200,000/mm³: Oral: 15 mg twice daily

Platelets 50,000 to <100,000/mm³: Oral: 5 mg twice daily

Dosage modification based on response in patients with baseline platelet count ≥100,000/mm³ prior to initial treatment with ruxolitinib: For insufficient response (with adequate platelet and neutrophil counts), may increase the dose in 5 mg twice daily increments to a maximum dose of 25 mg twice daily. Do not increase during initial 4 weeks and no more frequently than every 2 weeks. Discontinue treatment after 6 months if no reduction in spleen size or no improvement in symptoms. When discontinuing for reasons other than thrombocytopenia, consider gradually tapering by ~5 mg twice daily per week.

Dose increases may be considered if meet all of the following situations:

- Failure to achieve either a 50% reduction (from baseline) in palpable spleen length or a 35% reduction (from baseline) in spleen volume (measured by CT or MRI)

- Platelet count >125,000/mm³ at 4 weeks (and never <100,000/mm³)

- Absolute neutrophil count (ANC) >750/mm³

Dosage modification for bleeding requiring intervention (regardless of platelet count): Interrupt treatment until bleeding resolved; may consider resuming at the prior dose if the underlying cause of bleeding has resolved or at a reduced dose if the underlying cause of bleeding persists.

Dosage modification based on response in patients with baseline platelet 50,000 to <100,000/mm³ prior to initial treatment with ruxolitinib: For insufficient response (with adequate platelet and neutrophil counts), may increase the dose in 5 mg daily increments to a maximum dose of 10 mg twice daily. Do not increase during initial 4 weeks and no more frequently than every 2 weeks. Discontinue treatment after 6 months if no reduction in spleen size or no improvement in symptoms.

Dose increases may be considered if meet all of the following situations:

- Platelet count remains ≥40,000/mm³ and did not decrease more than 20% in prior 4 weeks

- Absolute neutrophil count (ANC) >1,000/mm³

- No adverse event or hematological toxicity resulting in dose reduction or interruption occurred in prior 4 weeks

Polycythemia vera

Polycythemia vera: Oral: Initial dose: 10 mg twice daily (titrate dose based on efficacy and safety)

Dose modification due to insufficient response: If response is insufficient and platelet, hemoglobin, and neutrophil counts are adequate, the dose may be increased in 5 mg twice daily increments to a maximum of 25 mg twice daily. Do not increase dose in the first 4 weeks of treatment and not more frequently than every 2 weeks. Consider dose increases in patients who meet all of the following conditions:

- Inadequate efficacy demonstrated by one or more of the following: Continued need for phlebotomy, WBC >ULN of normal range, platelet count >ULN of normal range, or palpable spleen that is reduced by <25% from baseline.

- Platelet count ≥140,000/mm³

- Hemoglobin ≥12 g/dL

- ANC ≥1,500/mm³

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

**Ruxolitinib Dosage Adjustments for Altered Kidney Function^a**
Kidney function status	Graft-versus-host disease		Myelofibrosis		Polycythemia vera
Kidney function status	*Acute, treatment, steroid refractory*	*Chronic, treatment, refractory*	Myelofibrosis		Polycythemia vera
^a After the initial dosing, additional dose adjustments should be made with frequent monitoring.
^bRuxolitinib is not removed by dialysis, although the removal of some active metabolites via dialysis cannot be ruled out.
CrCl ≥60 mL/minute	No dosage adjustment necessary.	No dosage adjustment necessary.	No dosage adjustment necessary.		No dosage adjustment necessary.
CrCl 15 to 59 mL/minute	Initial: 5 mg once daily	Initial: 5 mg twice daily	Platelets >150,000/mm³	No dosage adjustment necessary.	Initial: 5 mg twice daily
			Platelets 100,000 to 150,000/mm³	Initial: 10 mg twice daily
			Platelets 50,000 to <100,000/mm³	Initial: 5 mg once daily
			Platelets <50,000/mm³	Avoid use.
CrCl <15 mL/minute (not on dialysis)	Avoid use.	Avoid use.	Avoid use.		Avoid use.
Hemodialysis, intermittent^b	Initial: 5 mg administered after dialysis only on dialysis days	Initial: 10 mg administered after dialysis only on dialysis days	Platelets >200,000/mm³	Initial: 20 mg administered after dialysis only on dialysis days	Initial: 10 mg administered after dialysis only on dialysis days
Hemodialysis, intermittent^b			Platelets 100,000 to 200,000/mm³	Initial: 15 mg administered after dialysis only on dialysis days

Dosing: Liver Impairment: Adult

Graft-versus-host disease, acute, treatment, steroid-refractory:

Preexisting hepatic impairment:

Mild to severe impairment (based on NCI criteria) without liver acute graft-versus-host disease (aGVHD) and any platelet count: No dosage adjustment is necessary.

Stage 1, 2, or 3 liver aGVHD and any platelet count: No dosage adjustment is necessary.

Stage 4 liver aGVHD and any platelet count: 5 mg once daily.

Hepatoxicity during treatment (refer to "Dosing: Adjustment for Toxicity" for aGVHD dosage reduction levels):

Total bilirubin elevation without liver GVHD:

Total bilirubin 3 to 5 times ULN: Continue ruxolitinib at 1 dose level lower until recovery.

Total bilirubin >5 to 10 times ULN: Interrupt ruxolitinib treatment for up to 14 days. When bilirubin recovers to ≤1.5 times ULN, then resume at current dose.

Total bilirubin >10 times ULN: Interrupt ruxolitinib treatment for up to 14 days. When bilirubin recovers to ≤1.5 times ULN, then resume at 1 dose level lower.

Total bilirubin elevation with liver GVHD: Total bilirubin >3 times ULN: Continue ruxolitinib at 1 dose level lower until recovery.

Graft-versus-host disease, chronic, treatment, refractory:

Preexisting hepatic impairment:

Mild to severe impairment (based on NCI criteria) without liver chronic graft-versus-host disease (cGVHD) and any platelet count: No dosage adjustment is necessary.

Score 1 or 2 liver cGVHD and any platelet count: No dosage adjustment is necessary.

Score 3 liver cGVHD and any platelet count: Monitor blood counts more frequently for toxicity and modify the ruxolitinib dose for adverse reactions if they occur.

Hepatoxicity during treatment (refer to "Dosing: Adjustment for Toxicity" for cGVHD dosage reduction levels):

Total bilirubin 3 to 5 times ULN: Continue ruxolitinib at 1 dose level lower until recovery. If resolved within 14 days, then increase by 1 dose level. If not resolved within 14 days, maintain the decreased dose level.

Total bilirubin >5 to 10 times ULN: Interrupt ruxolitinib treatment for up to 14 days until resolved, then resume at the current dose upon recovery. If not resolved within 14 days, then resume at 1 dose level lower upon recovery.

Total bilirubin >10 times ULN: Interrupt ruxolitinib treatment for up to 14 days until resolved, then resume at 1 dose level lower upon recovery. If not resolved within 14 days, discontinue ruxolitinib.

Myelofibrosis:

Mild to severe impairment (Child-Pugh class A, B, or C) and platelets >150,000/mm³: No dosage adjustment is necessary.

Mild to severe impairment (Child-Pugh class A, B, or C) and platelets 100,000 to 150,000/mm³: Initial dose: 10 mg twice daily; additional dose adjustments should be made with careful monitoring.

Mild to severe impairment (Child-Pugh class A, B, or C) and platelets 50,000 to <100,000/mm³: Initial dose: 5 mg once daily; additional dose adjustments should be made with careful monitoring.

Mild to severe impairment (Child-Pugh class A, B, or C) and platelets <50,000/mm³: Avoid use.

Polycythemia vera: Mild to severe impairment (Child-Pugh class A, B, or C) and any platelet count: Initial dose: 5 mg twice daily; additional dose adjustments should be made with careful monitoring.

Dosing: Adjustment for Toxicity: Adult

Note: Platelet and/or blood transfusions may be administered during treatment if clinically indicated.

Graft-versus-host disease, acute, treatment, steroid-refractory:

Dosage reduction levels:

If dose is 10 mg twice daily, reduce dose to 5 mg twice daily.

If dose is 5 mg twice daily, reduce dose to 5 mg once daily.

If unable to tolerate 5 mg once daily, interrupt ruxolitinib treatment until clinical and/or laboratory parameters recover.

Dosage modification for hematologic toxicity in acute graft-versus-host disease:

Clinically significant thrombocytopenia (after supportive measures): Reduce dose by 1 dose level; when platelets recover to previous values, may increase dose to prior dose level.

ANC <1,000/mm³ (related to ruxolitinib treatment): Interrupt treatment for up to 14 days. Resume at 1 dose level lower when ANC recovers.

Graft-versus-host disease, chronic, refractory:

Dosage reduction levels:

If dose is 10 mg twice daily, reduce dose to 5 mg twice daily.

If dose is 5 mg twice daily, reduce dose to 5 mg once daily.

If unable to tolerate 5 mg once daily, interrupt ruxolitinib treatment until clinical and/or laboratory parameters recover.

**Ruxolitinib Dose Modifications for Adverse Reactions in Chronic Graft-Versus-Host Disease**
Adverse reaction	Ruxolitinib dosing recommendation
Hematologic toxicity
Platelets <20,000/mm³	Reduce ruxolitinib by 1 dose level. If resolved within 7 days, may increase dose to initial dose level. If not resolved within 7 days, then maintain dose at 1 dose level lower than initial dose.
ANC <750/mm³ (if considered related to ruxolitinib)	Reduce ruxolitinib by 1 dose level; resume at initial dose level upon recovery.
ANC <500/mm³ (if considered related to ruxolitinib)	Hold ruxolitinib for up to 14 days; resume at 1 dose level lower upon recovery. May resume initial dose level when ANC >1,000/mm³.
Other adverse reactions
Grade 3	Continue ruxolitinib at 1 dose level lower until recovery.
Grade 4	Discontinue ruxolitinib.

Myelofibrosis:

Dosage modification for treatment interruption:

If baseline platelet count ≥100,000/mm³ prior to initial treatment with ruxolitinib and:

Platelets <50,000/mm³ or ANC <500/mm³: Interrupt treatment; upon platelet recovery (to ≥50,000/mm³) or ANC recovery (to ≥750/mm³), dosing may be restarted or increased based on the following platelet or ANC levels:

Platelets ≥125,000/mm³: Dose should be at least 5 mg twice daily below the dose at treatment interruption, up to a maximum of 20 mg twice daily

Platelets 100,000 to <125,000/mm³: Dose should be at least 5 mg twice daily below the dose at treatment interruption, up to a maximum of 15 mg twice daily

Platelets 75,000 to <100,000/mm³: Dose should be at least 5 mg twice daily below the dose at treatment interruption, up to a maximum of 10 mg twice daily for at least 2 weeks; may increase to 15 mg twice daily if stable

Platelets 50,000 to <75,000/mm³: 5 mg twice daily for at least 2 weeks; may increase to 10 mg twice daily if stable

Platelets <50,000/mm³: Continue to withhold treatment

ANC ≥750/mm³: Resume at 5 mg once daily or 5 mg twice daily below the largest dose in the week prior to treatment interruption, whichever is greater

Note: Long-term maintenance at 5 mg twice daily has not demonstrated responses; limit use of the dose level to patients where the benefits outweigh risks

If baseline platelet count 50,000 to <100,000/mm³ prior to initial treatment with ruxolitinib and:

Platelets <25,000/mm³ or ANC <500/mm³: Interrupt treatment; upon platelet recovery (to ≥35,000/mm³) or ANC recovery (to ≥750/mm³), resume at 5 mg once daily or 5 mg twice daily below the largest dose in the week prior to treatment interruption, whichever is greater

Note: Long-term maintenance at 5 mg twice daily has not demonstrated responses; limit use of the dose level to patients where the benefits outweigh risks

Dosage reduction for thrombocytopenia in patients with baseline platelet count ≥100,000/mm³ prior to initial treatment with ruxolitinib:

**Ruxolitinib Initial Dosage Reduction for Thrombocytopenia in Patients With Myelofibrosis With Baseline Platelets ≥100,000/mm³**
	Dose at time of thrombocytopenia
Note: Long-term maintenance at 5 mg twice daily has not demonstrated responses; limit use of the dose level to patients where the benefits outweigh risks
	25 mg twice/day	20 mg twice/day	15 mg twice/day	10 mg twice/day	5 mg twice/day
Platelet Count	New Dose	New Dose	New Dose	New Dose	New Dose
100,000 to <125,000/mm³	20 mg twice/day	15 mg twice/day	No change	No change	No change
75,000 to <100,000/mm³	10 mg twice/day	10 mg twice/day	10 mg twice/day	No change	No change
50,000 to <75,000/mm³	5 mg twice/day	5 mg twice/day	5 mg twice/day	5 mg twice/day	No change
<50,000/mm³	Hold dose	Hold dose	Hold dose	Hold dose	Hold dose

Dosage reduction for thrombocytopenia in patients with baseline platelet 50,000 to <100,000/mm³ prior to initial treatment with ruxolitinib:

**Ruxolitinib Initial Dosage Reduction for Thrombocytopenia in Patients With Myelofibrosis With Baseline Platelets 50,000/mm³ to <100,000/mm³**
Platelet count	Dosing recommendations
<25,000/mm³	Interrupt dosing
25,000 to <35,000/mm³ AND platelet count decline <20% during prior 4 weeks	Decrease dose by 5 mg once daily. For patients on 5 mg once daily, maintain dose at 5 mg once daily.
25,000 to <35,000/mm³ AND platelet count decline ≥20% during prior 4 weeks	Decrease dose by 5 mg twice daily. For patients on 5 mg twice daily, decrease the dose to 5 mg once daily. For patients on 5 mg once daily, maintain dose at 5 mg once daily.
Note: Long-term maintenance at 5 mg twice daily has not demonstrated responses (based on limited data); limit use of the dose level to patients where the benefits outweigh the risks.

Polycythemia vera:

**Ruxolitinib Dosage Adjustment for Hematologic Toxicity in Patients With Polycythemia Vera**
Hematologic parameter	Dosing recommendations
Hemoglobin ≥12 g/dL AND platelets ≥100,000/mm³	No dosage adjustment necessary.
Hemoglobin 10 to <12 g/dL AND platelets 75,000 to < 100,000/mm³	Consider dosage reduction to avoid dose interruptions due to anemia and thrombocytopenia.
Hemoglobin 8 to <10 g/dL OR platelets 50,000 to <75,000/mm³	Reduce dose by 5 mg twice daily; for patients currently receiving 5 mg twice daily, reduce dose to 5 mg once daily.
Hemoglobin <8 g/dL OR platelets <50,000/mm³ OR ANC <1,000/mm³	Interrupt dosing.

Dosage reduction following treatment interruption (use the most severe category of hemoglobin, platelets, or ANC to determine reinitiation dose):

**Ruxolitinib Dose Reinitiation after Interruption for Hematologic Toxicity in Patients With Polycythemia Vera**
Hematologic parameter	Maximum restarting dose
^aContinue treatment for at least 2 weeks; if stable, may increase dose by 5 mg twice daily.
Hemoglobin <8 g/dL OR Platelets <50,000/mm³ OR ANC <1,000/mm³	Continue to hold.
Hemoglobin 8 to <10 g/dL OR platelets 50,000 to <75,000/mm³ OR ANC 1,000 to <1,500/mm³	5 mg twice daily^a or no more than 5 mg twice daily less than the dose that resulted in dose interruption.
Hemoglobin 10 to <12 g/dL OR platelets 75,000 to <100,000/mm³ OR ANC 1,500 to <2,000/mm³	10 mg twice daily^a or no more than 5 mg twice daily less than the dose that resulted in dose interruption.
Hemoglobin ≥12 g/dL OR platelets ≥100,000/mm³ OR ANC ≥2,000/mm³	15 mg twice daily^a or no more than 5 mg twice daily less than the dose that resulted in dose interruption.
Note: If dose interruption was required while receiving 5 mg twice daily, may restart at 5 mg twice daily or 5 mg once daily (but not higher) once hemoglobin is ≥10 g/dL, platelets are ≥75,000/mm³, and ANC is ≥1,500/mm³.
*Dose management after restarting treatment:*After restarting following a dose interruption, the dose may be titrated, although the maximum total daily dose should not exceed 5 mg less than the dose resulting in the interruption (unless dose interruption following phlebotomy-associated anemia, in which case the maximum total daily dose is not limited).

Other ruxolitinib adverse reactions:

Hyperlipidemia: Manage as appropriate according to clinical practice guidelines.

Infection: Treat promptly if symptoms of tuberculosis (TB) disease (active TB) and/or herpes zoster infection develop. If evidence of herpes simplex dissemination, consider interrupting ruxolitinib treatment; treat promptly. For patients with evidence of TB (disease or infection [latent TB]), decide risk-benefit of continuing treatment.

Progressive multifocal leukoencephalopathy: Discontinue ruxolitinib and evaluate if progressive multifocal leukoencephalopathy is suspected.

Thrombosis: Promptly evaluate and manage as appropriate.

Withdrawal syndrome (in myeloproliferative neoplasms): Evaluate and treat any concurrent illness and consider restarting or increasing ruxolitinib dose. Consider gradually tapering off if discontinuing for reasons other than thrombocytopenia or neutropenia.

Dosing: Pediatric

(For additional information see "Ruxolitinib (systemic): Pediatric drug information")

Graft-versus-host disease, acute

Graft-versus-host disease, acute (aGVHD): Note: If appropriate, utilize prophylactic antibiotics according to clinical practice guidelines. Delay initiating ruxolitinib until after active infections have resolved.

Initiation of therapy:

Fixed dosing:

Children ≥2 years to <6 years: Limited data available: Oral: Initial: 4 mg/m²/dose twice daily. Note: Dosing based on results of the REACH4 trial, a prospective study which confirmed dosing and efficacy end points at 24 and 56 weeks (Ref).

Children ≥6 years to <12 years: Limited data available: Oral: Initial: 5 mg twice daily. Note: Dosing based on results of the REACH4 trial, a prospective study which confirmed dosing and efficacy end points at 24 and 56 weeks (Ref).

Children ≥12 years and Adolescents: Oral: Initial: 5 mg twice daily. Consider increasing the dose to 10 mg twice daily after at least 3 days of treatment if ANC and platelets are not decreased by ≥50% compared to baseline (first day of ruxolitinib).

Weight-band dosing: Limited data available: Note: Dosing based on a retrospective study of 13 patients (aged 1.6 to 16.5 years) receiving ruxolitinib for steroid-refractory aGVHD. Ruxolitinib was associated with a high incidence of reversible adverse effects and fair overall response rate (Ref).

Children and Adolescents:

<25 kg: Oral: Initial: 2.5 mg twice daily; if tolerated, may double the dose on a weekly basis to a maximum dose of 10 mg twice daily.

≥25 kg: Oral: Initial: 5 mg twice daily; if tolerated, may double the dose on a weekly basis to a maximum dose of 10 mg twice daily.

Tapering of therapy: Consider tapering ruxolitinib after 6 months of therapy if response occurs and therapeutic corticosteroid doses have been discontinued; taper by 1 dose level approximately every 8 weeks (eg, 10 mg twice daily to 5 mg twice daily to 5 mg once daily) (Ref). Consider retreatment if aGVHD signs or symptoms recur during or after tapering ruxolitinib (Ref).

Graft-versus-host disease, chronic

Graft-versus-host disease, chronic (cGVHD): Note: Reserve for treatment following failure of 1 or 2 previous systemic lines of therapy. If appropriate, utilize prophylactic antibiotics according to clinical practice guidelines. Delay initiating ruxolitinib until after active infections have resolved.

Initiation of therapy:

Children ≥2 years to <6 years: Limited data available: Oral: 4 mg/m²/dose twice daily. Note: Dosing based on results of the REACH 5 trial, a prospective study which reported at interim (either 1 year of therapy or discontinuation) an overall response rate of 28.6% in patients 2 to <6 years of age (n=7) (Ref).

Children ≥6 years to <12 years: Limited data available: Oral: 5 mg twice daily. Note: Dosing based on results of the REACH 5 trial, a prospective study which reported at interim (either 1 year of therapy or discontinuation) an overall response rate of 50% in patients 6 to <12 years of age (n=16) (Ref).

Children ≥12 years and Adolescents: Oral: 10 mg twice daily (Ref).

Tapering of therapy: Consider tapering ruxolitinib after 6 months of therapy if response occurs and therapeutic corticosteroid doses have been discontinued; taper by 1 dose level approximately every 8 weeks (eg, 10 mg twice daily to 5 mg twice daily to 5 mg once daily). Consider retreatment if cGVHD signs/symptoms recur during or after tapering ruxolitinib (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing adjustment for toxicity:

Graft-versus-host disease; acute (aGVHD): Note: Specific recommendations for pediatric patients <12 years of age are limited; refer to specific protocol for management, particularly for myelosuppression (thrombocytopenia and neutropenia).

Children ≥12 years and Adolescents: Oral:

Dosage reduction levels:

Note: Dosage reduction is based on ruxolitinib regimen at time of toxicity.

If dose is 10 mg twice daily, reduce dose to 5 mg twice daily.

If dose is 5 mg twice daily, reduce dose to 5 mg once daily.

If dose is 5 mg once daily, interrupt ruxolitinib treatment until clinical and/or laboratory parameters recover.

Dosage modification for hematologic toxicity:

Clinically significant thrombocytopenia: Reduce dose by 1 dose level; when platelets recover to previous values, may increase dose to prior dose level.

ANC <1,000/mm³ related to ruxolitinib treatment: Interrupt treatment for up to 14 days; upon recovery, restart at 1 dose level lower.

Graft-versus-host disease; chronic (cGVHD): Note: Specific recommendations for pediatric patients <12 years of age are limited; refer to specific protocol for management, particularly for myelosuppression (thrombocytopenia and neutropenia).

Children ≥12 years and Adolescents: Oral:

Dosage reduction levels:

Note: Dosage reduction is based on ruxolitinib regimen at time of toxicity.

If dose is 10 mg twice daily, reduce dose to 5 mg twice daily.

If dose is 5 mg twice daily, reduce dose to 5 mg once daily.

If unable to tolerate 5 mg once daily, interrupt ruxolitinib treatment until clinical and/or laboratory parameters recover.

**Ruxolitinib Dosage Adjustment for Toxicity in Chronic Graft-Versus-Host Disease**
Adverse reaction	Ruxolitinib dosing recommendation
*Hematologic toxicity*
Platelets <20,000/mm³	Reduce ruxolitinib by 1 dose level. If resolved within 7 days, may increase dose to initial dose level. If not resolved within 7 days, then maintain dose at 1 dose level lower than initial dose.
ANC <750/mm³ (if considered related to ruxolitinib)	Reduce ruxolitinib by 1 dose level; resume at initial dose level upon recovery.
ANC <500/mm³ (if considered related to ruxolitinib)	Hold ruxolitinib for up to 14 days; resume at 1 dose level lower upon recovery. May resume initial dose level when ANC >1,000/mm³.
*Other adverse reactions (excluding hepatotoxicity)*
Grade 3	Continue ruxolitinib at 1 dose level lower until recovery.
Grade 4	Discontinue ruxolitinib.

Dosing: Kidney Impairment: Pediatric

Graft-versus-host disease; acute (aGVHD):

Children ≥12 years and Adolescents: Oral:

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl 15 to 59 mL/minute and any platelet count: Initial: 5 mg once daily.

Dialysis: Ruxolitinib not removed by dialysis, effect on metabolites unknown.

End-stage renal disease (ESRD) (CrCl <15 mL/minute) on dialysis and any platelet count: Initial: 5 mg once after dialysis; monitor closely for safety and efficacy and make additional dose adjustments as needed.

ESRD (CrCl <15 mL/minute) not requiring dialysis: Avoid use.

Graft-versus-host disease; chronic (cGVHD):

Children ≥12 years and Adolescents: Oral:

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl 15 to 59 mL/minute and any platelet count: Initial: 5 mg twice daily. Additional dose adjustments should be made with frequent monitoring.

ESRD (CrCl <15 mL/minute) on dialysis and any platelet count: Initial dose: 10 mg once after dialysis; additional dose adjustments should be made with careful monitoring.

ESRD (CrCl <15 mL/minute) not requiring dialysis: Avoid use.

Dosing: Liver Impairment: Pediatric

Graft-versus-host disease; acute (aGVHD):

Children ≥12 years and Adolescents: Oral:

Dosage reduction levels:

Note: Dosage reduction is based on ruxolitinib regimen at time of toxicity.

If dose is 10 mg twice daily, reduce dose to 5 mg twice daily.

If dose is 5 mg twice daily, reduce dose to 5 mg once daily.

If dose is 5 mg once daily, interrupt ruxolitinib treatment until clinical and/or laboratory parameters recover.

Hepatic impairment prior to initiation (baseline):

Mild to severe hepatic impairment (based on NCI criteria) without liver aGVHD and any platelet count: No dosage adjustment is necessary.

Stage 1, 2, or 3 liver aGVHD and any platelet count: No dosage adjustment is necessary.

Stage 4 liver aGVHD and any platelet count: Reduce dose to 5 mg once daily.

Hepatoxicity during treatment:

Total bilirubin elevation without liver GVHD:

Total bilirubin 3 to 5 × ULN: Reduce dose by 1 dose level until total bilirubin recovers.

Total bilirubin >5 to 10 × ULN: Interrupt ruxolitinib treatment for up to 14 days; when bilirubin recovers to ≤1.5 × ULN, may restart at current dose.

Total bilirubin >10 × ULN: Interrupt ruxolitinib treatment for up to 14 days; when bilirubin recovers to ≤1.5 × ULN, may restart at 1 dose level lower.

Total bilirubin elevation with liver GVHD: Total bilirubin >3 × ULN: Reduce dose 1 dose level until total bilirubin recovers.

Graft-versus-host disease; chronic (cGVHD):

Children ≥12 years and Adolescents: Oral:

Dosage reduction levels:

If dose is 10 mg twice daily, reduce dose to 5 mg twice daily.

If dose is 5 mg twice daily, reduce dose to 5 mg once daily.

If unable to tolerate 5 mg once daily, interrupt ruxolitinib treatment until clinical and/or laboratory parameters recover.

Hepatic impairment prior to initiation (baseline):

Mild to severe impairment (based on NCI criteria) without liver cGVHD and any platelet count: No dosage adjustment is necessary.

Score 1 or 2 liver cGVHD and any platelet count: No dosage adjustment is necessary.

Score 3 liver cGVHD and any platelet count: Monitor blood counts more frequently for toxicity and modify the ruxolitinib dose for adverse reactions if they occur.

Hepatoxicity during treatment :

Total bilirubin 3 to 5 × ULN: Continue ruxolitinib at 1 dose level lower until recovery. If resolved within 14 days, then increase by 1 dose level. If not resolved within 14 days, maintain the decreased dose level.

Total bilirubin >5 to 10 × ULN: Interrupt ruxolitinib treatment for up to 14 days until resolved, then resume at the current dose upon recovery. If not resolved within 14 days, then resume at 1 dose level lower upon recovery.

Total bilirubin >10 × ULN: Interrupt ruxolitinib treatment for up to 14 days until resolved, then resume at 1 dose level lower upon recovery. If not resolved within 14 days, discontinue ruxolitinib.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Hypertension (5% to 16%)

Endocrine & metabolic: Hypercholesteremia (17% to 88%), hypertriglyceridemia (15%)

Gastrointestinal: Diarrhea (10% to 15%), nausea (6% to 12%)

Hematologic & oncologic: Anemia (72% to 96%; grades 3/4: ≤34%), bruise (23%), hemorrhage (12%), neutropenia (3% to 19%; grades 3/4: ≤12%), thrombocytopenia (27% to 70%; grades 3/4: ≤20%)

Hepatic: Increased serum alanine aminotransferase (25% to 73%), increased serum aspartate aminotransferase (17% to 65%)

Infection: Infection (45%), viral infection (28%)

Nervous system: Dizziness (15% to 18%), fatigue (13%), headache (15%)

Neuromuscular & skeletal: Muscle spasm (12%), musculoskeletal pain (18%)

Respiratory: Cough (13%), dyspnea (11% to 13%)

Miscellaneous: Fever (16%)

1% to 10%:

Cardiovascular: Edema (10%)

Endocrine & metabolic: Weight gain (6% to 7%)

Gastrointestinal: Constipation (8%), flatulence (5%)

Genitourinary: Urinary tract infection (6% to 9%)

Infection: Herpes zoster infection (2% to 6%)

Frequency not defined:

Dermatologic: Basal cell carcinoma of skin, Merkel cell carcinoma, skin carcinoma, squamous cell carcinoma of skin

Endocrine & metabolic: Increased LDL cholesterol

Infection: Serious infection

Nervous system: Progressive multifocal leukoencephalopathy

Postmarketing:

Hepatic: Exacerbation of hepatitis B

Infection: Herpes simplex infection (reactivation and/or dissemination)

Nervous system: Insomnia (Ref)

Respiratory: Tuberculosis

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Hypersensitivity to ruxolitinib or any component of the formulation or container; history of or current progressive multifocal leukoencephalopathy.

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac effects: The risk for major adverse cardiovascular events, including cardiovascular death, myocardial infarction, and stroke was increased with use of another Janus kinase (JAK)-inhibitor (as compared to tumor necrosis factor [TNF] blockers) in patients treated for rheumatoid arthritis (not an approved indication for ruxolitinib). Inform patients of the symptoms of serious cardiovascular events.

• Hematologic toxicity: Hematologic toxicity, including thrombocytopenia, anemia and neutropenia may occur with ruxolitinib. Thrombocytopenia and neutropenia (ANC <500/mm³) are generally reversible with treatment interruption or dose reduction.

• Infections: Serious bacterial, mycobacterial (including tuberculosis), fungal, and/or viral infections have occurred. Active serious infections should be resolved prior to ruxolitinib treatment initiation. Progressive multifocal leukoencephalopathy (PML) has been reported. Hepatitis B viral load (HBV-DNA titer) increases (with and without associated ALT or AST elevations) have been reported with ruxolitinib in patients with chronic hepatitis B infection, although the effect of ruxolitinib is unknown. Herpes zoster infection, as well as herpes simplex virus reactivation and/or dissemination, have been reported.

• Lipid abnormalities: Ruxolitinib has been associated with increases in lipid parameters (eg, total cholesterol, LDL cholesterol, and triglycerides).

• Secondary malignancy: Nonmelanoma skin cancers (basal cell, squamous cell, and Merkel cell carcinoma) have been reported in patients who have received ruxolitinib. The risk for lymphoma and other malignancies (excluding nonmelanoma skin cancer) was increased with use of another JAK-inhibitor (as compared to TNF blockers) in patients treated for rheumatoid arthritis (not an approved indication for ruxolitinib). Patients who are current or past smokers are at additional increased risk.

• Thrombosis: The risk for thrombosis, including deep venous thrombosis, pulmonary embolism, and arterial thrombosis, has increased with use of another JAK-inhibitor (as compared to TNF blockers) in patients treated for rheumatoid arthritis (not an approved indication for ruxolitinib).

Other warnings/precautions:

• Withdrawal syndrome: Acute relapse of myelofibrosis symptoms (eg, fever, respiratory distress, hypotension, DIC, multiorgan failure), splenomegaly, worsening cytopenias, hemodynamic decompensation, and septic shock-like syndrome have been reported with treatment tapering or discontinuation (Tefferi 2011). Symptoms generally return over approximately 1 week. Patients should not interrupt/discontinue treatment without consulting healthcare provider.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Jakafi: 5 mg, 10 mg, 15 mg, 20 mg, 25 mg

Generic Equivalent Available: US

Pricing: US

Tablets (Jakafi Oral)

5 mg (per each): $352.00

10 mg (per each): $352.00

15 mg (per each): $352.00

20 mg (per each): $352.00

25 mg (per each): $352.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Jakavi: 5 mg, 10 mg, 15 mg, 20 mg

Prescribing and Access Restrictions

Available through specialty/network pharmacies. Further information may be obtained from the manufacturer, Incyte, at 1-855-452-5234 or at www.Jakafi.com.

Administration: Adult

Oral: May be administered with or without food. If a dose is missed, return to the usual dosing schedule and do not administer an additional dose.

If unable to ingest tablets, may administer through a nasogastric (NG) tube (≥8 Fr): Suspend 1 tablet in ~40 mL water and stir for ~10 minutes and administer (within 6 hours after dispersion) with appropriate syringe; rinse NG tube with ~75 mL water (effect of enteral tube feeding on ruxolitinib exposure has not been evaluated).

Administration: Pediatric

Oral: Tablets: May be administered with or without food.

Administration via feeding tube: Tablets: If unable to ingest tablets, may administer through a nasogastric (NG) tube (≥8 Fr): Suspend 1 tablet in ~40 mL water and stir for ~10 minutes and administer (within 6 hours after dispersion) with appropriate syringe; rinse NG tube with ~75 mL water (effect of enteral tube feeding on ruxolitinib exposure has not been evaluated).

Missed dose: If a dose is missed, return to the usual dosing schedule and do not administer an additional dose.

Use: Labeled Indications

Graft-versus-host disease, acute: Treatment of steroid-refractory acute graft-versus-host disease (aGVHD) in adult and pediatric patients ≥12 years.

Graft-versus-host disease, chronic: Treatment of chronic graft-versus-host disease (cGVHD) after failure of one or two lines of systemic therapy in adult and pediatric patients ≥12 years of age.

Myelofibrosis: Treatment of intermediate or high-risk myelofibrosis in adults, including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.

Polycythemia vera: Treatment of polycythemia vera in adults with an inadequate response to or intolerance to hydroxyurea.

Medication Safety Issues

Sound-alike/look-alike issues:

Ruxolitinib may be confused with cabozantinib, fedratinib, pacritinib, PONATinib, regorafenib, ripretinib, riTUXimab, rucaparib, tofacitinib.

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).

Metabolism/Transport Effects

Substrate of CYP2C9 (Minor), CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor

Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor

Azithromycin (Systemic): May increase serum concentration of Ruxolitinib (Systemic). Risk C: Monitor

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor

Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid

Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor

Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid

Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor

CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor

Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor

CYP3A4 Inducers (Strong): May decrease serum concentration of Ruxolitinib (Systemic). CYP3A4 Inducers (Strong) may increase active metabolite exposure of Ruxolitinib (Systemic). Risk C: Monitor

CYP3A4 Inhibitors (Moderate): May increase serum concentration of Ruxolitinib (Systemic). Risk C: Monitor

CYP3A4 Inhibitors (Strong): May increase serum concentration of Ruxolitinib (Systemic). Management: This combination should be avoided under some circumstances; dose adjustments may be required in some circumstances and depend on the indication for ruxolitinib. See monograph for details. Risk D: Consider Therapy Modification

Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification

Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid

Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Fluconazole: May increase serum concentration of Ruxolitinib (Systemic). Management: Avoid fluconazole doses over 200 mg/day in combination with ruxolitinib. Dose adjustments are required in some circumstances. See full interaction monograph for details. Risk D: Consider Therapy Modification

Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification

Grapefruit Juice: May increase serum concentration of Ruxolitinib (Systemic). Risk C: Monitor

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification

Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor

Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor

Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification

Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid

Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification

Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid

Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid

Food Interactions

Grapefruit juice may increase the effects of ruxolitinib. Management: Avoid grapefruit juice.

Pregnancy Considerations

Based on data from animal reproduction studies, ruxolitinib may cause fetal harm if administered during pregnancy. Use of ruxolitinib in pregnant patients is not recommended; other agents are preferred for management of polycythemia vera and myeloproliferative disease (Gerds 2017; Kiladjian 2015).

Breastfeeding Considerations

It is not known if ruxolitinib is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, discontinue breastfeeding during ruxolitinib treatment and for 2 weeks after the final ruxolitinib dose.

Dietary Considerations

Avoid grapefruit juice (may increase the effects of ruxolitinib).

Monitoring Parameters

CBC (baseline, every 2 to 4 weeks until dose stabilized, then as clinically indicated; monitor blood counts more frequently in patients with stage 3 or 4 liver graft-versus-host disease [GVHD]), lipid parameters (8 to 12 weeks after ruxolitinib initiation and as appropriate thereafter), kidney function, hepatic function (including bilirubin in patients with GVHD; prior to treatment and every 2 to 4 weeks until dose stabilized, then as clinically indicated). Monitor hepatitis B viral load (HBV-DNA titer) in patients with chronic hepatitis B infection. Perform periodic skin examinations. Monitor for signs/symptoms of infection and secondary malignancy. Perform tuberculin skin test (prior to initiation); patients at higher risk for tuberculosis (TB) (prior residence/travel to countries with a high TB prevalence, close contacts with TB disease [active TB], or history of TB infection [latent TB] or TB disease where adequate treatment course cannot be confirmed) should be tested for TB infection. Assess history of past infections, including herpes simplex, herpes zoster, and hepatitis B. Monitor for signs/symptoms of thrombosis and for major adverse cardiovascular events, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Ruxolitinib is a kinase inhibitor which selectively inhibits Janus Associated Kinases (JAKs), JAK1 and JAK2. JAK1 and JAK2 mediate signaling of cytokine and growth factors responsible for hematopoiesis and immune function; JAK mediated signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors which leads to modulation of gene expression. In myelofibrosis and polycythemia vera, JAK1/2 activity is dysregulated; ruxolitinib modulates the affected JAK1/2 activity. JAK-STAT signaling is involved with the regulation of the development, proliferation, and activation of immune cell types important to GVHD pathogenesis; an animal model suggests that ruxolitinib may lead to decreased expression of inflammatory cytokines in colon homogenates and decreased immune cell infiltration in the colon.

Pharmacokinetics (Adult Data Unless Noted)

Onset:

Acute graft-versus-host disease (GVHD): Median time to response: 1.5 weeks (range: 1 to 11 weeks) (Zeiser 2015).

Chronic GVHD: Median time to response: 3 weeks (range: 1 to 25 weeks) (Zeiser 2015); responses were observed within 2 weeks of ruxolitinib initiation in another study (Khoury 2018).

Absorption: Rapid.

Distribution: V_d: Myelofibrosis: 72 L; Polycythemia vera: 75 L.

Protein binding: ~97%; primarily to albumin.

Metabolism: Hepatic, primarily via CYP3A4 (and minimally CYP2C9); forms active metabolites responsible for 20% to 50% of activity.

Half-life elimination: Ruxolitinib: ~3 hours; Ruxolitinib + metabolites: ~5.8 hours.

Time to peak: Within 1 to 2 hours.

Excretion: Urine (74%, <1% as unchanged drug); feces (22%, <1% as unchanged drug).

Clearance: Myelofibrosis: 17.7 to 22.1 L/hour; polycythemia vera: 12.7 L/hour; acute graft-versus-host disease: 11.8 L/hour; chronic graft-versus-host disease: 9.7 L/hour.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: The total AUC of ruxolitinib (and active metabolites) increased by 1.3-, 1.5-, and 1.9-fold in subjects with mild, moderate, or severe kidney impairment, respectively, compared to those with CrCl ≥90 mL/minute. Total AUC of ruxolitinib and active metabolites increased 1.6-fold in subjects with ESRD requiring dialysis (compared to those with CrCl ≥90 mL/minute).

Hepatic function impairment: Ruxolitinib AUC increased by 1.9-, 1.3-, and 1.7-fold in subjects with Child-Pugh class A, Child-Pugh class B, or Child-Pugh class C hepatic impairment, respectively, compared to subjects with normal hepatic function.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Jakavi;
(AR) Argentina: Jakavi;
(AT) Austria: Jakavi;
(AU) Australia: Jakavi;
(BE) Belgium: Jakavi;
(BG) Bulgaria: Jakavi;
(BR) Brazil: Jakavi;
(CH) Switzerland: Jakavi;
(CL) Chile: Jakavi;
(CO) Colombia: Jakavi;
(CZ) Czech Republic: Jakavi;
(DE) Germany: Jakavi;
(DO) Dominican Republic: Jakavi;
(EC) Ecuador: Jakavi | Ruxolitinib;
(EE) Estonia: Jakavi;
(EG) Egypt: Jakavi;
(ES) Spain: Jakavi;
(FI) Finland: Jakavi;
(FR) France: Jakavi;
(GB) United Kingdom: Jakavi;
(GR) Greece: Jakavi;
(HK) Hong Kong: Jakavi;
(HR) Croatia: Jakavi;
(HU) Hungary: Jakavi;
(ID) Indonesia: Jakavi;
(IE) Ireland: Jakavi;
(IN) India: Jakavi;
(IT) Italy: Jakavi | Ruxolitinib;
(JO) Jordan: Jakavi;
(JP) Japan: Jakavi;
(KE) Kenya: Jakavi;
(KR) Korea, Republic of: Jakavi;
(KW) Kuwait: Jakavi;
(LB) Lebanon: Jakavi;
(LT) Lithuania: Jakavi;
(LV) Latvia: Jakavi;
(MA) Morocco: Jakavi;
(MX) Mexico: Jakavi;
(MY) Malaysia: Jakavi;
(NG) Nigeria: Jakavi;
(NL) Netherlands: Jakavi;
(NO) Norway: Jakavi;
(NZ) New Zealand: Jakavi;
(PE) Peru: Jakavi;
(PH) Philippines: Jakavi;
(PK) Pakistan: Jakavi;
(PL) Poland: Jakavi;
(PR) Puerto Rico: Jakafi;
(PT) Portugal: Jakavi;
(PY) Paraguay: Jakavi;
(QA) Qatar: Jakavi;
(RO) Romania: Jakavi;
(RU) Russian Federation: Jakavi;
(SA) Saudi Arabia: Jakavi;
(SE) Sweden: Jakavi;
(SG) Singapore: Jakavi;
(SI) Slovenia: Jakavi;
(SK) Slovakia: Jakavi;
(TH) Thailand: Jakavi;
(TN) Tunisia: Jakavi;
(TR) Turkey: Jakavi;
(TW) Taiwan: Jakavi;
(UA) Ukraine: Jakavi;
(UG) Uganda: Jakavi;
(UY) Uruguay: Jakavi;
(ZA) South Africa: Jakavi

Cervantes F, Vannucchi AM, Kiladjian JJ, et al; COMFORT-II investigators. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013;122(25):4047-4053. [PubMed 24174625]
Chen X, Williams WV, Sandor V, Yeleswaram S. Population pharmacokinetic analysis of orally-administered ruxolitinib (INCB018424 Phosphate) in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF) or post-essential thrombocythemia myelofibrosis (PET MF). J Clin Pharmacol. 2013;53(7):721-730. [PubMed 23677817]
Gerds AT, Dao KH. Polycythemia vera management and challenges in the community health setting. Oncology. 2017;92(4):179-189. doi:10.1159/000454953 [PubMed 28095380]
Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition With Ruxolitinib versus Best Available Therapy for Myelofibrosis. N Engl J Med. 2012;366(9):787-798. doi:10.1002/jcph.102 [PubMed 22375970]
Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
Jakafi (ruxolitinib) [prescribing information]. Wilmington, DE: Incyte Corporation; January 2023.
Jakavi (ruxolitinib) [product monograph]. Montreal, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; April 2023.
Khandelwal P, Teusink-Cross A, Davies SM, et al. Ruxolitinib as salvage therapy in steroid-refractory acute graft-versus-host disease in pediatric hematopoietic stem cell transplant patients. Biol Blood Marrow Transplant. 2017;23(7):1122-1127. doi:10.1016/j.bbmt.2017.03.029 [PubMed 28344057]
Kiladjian JJ. Current therapies and their indications for the Philadelphia-negative myeloproliferative neoplasms. Am Soc Clin Oncol Educ Book. 2015:389-396. doi:10.14694/EdBook_AM.2015.35.e389 [PubMed 25993201]
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Refer to manufacturer's labeling.
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Ruxolitinib (systemic): Drug information