Version May 2024
Note: If appropriate, utilize prophylactic antibiotics according to clinical practice guidelines. Delay initiating ruxolitinib until after active infections have resolved. If discontinuing ruxolitinib for reasons other than thrombocytopenia, consider gradually tapering off (by 5 mg twice daily each week).
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: 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: 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: 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.
Graft-versus-host disease, acute, treatment, steroid-refractory:
CrCl 15 to 59 mL/minute and any platelet count: Initial: 5 mg once daily. Additional dose adjustments should be made with frequent monitoring.
End-stage renal disease (ESRD) (CrCl <15 mL/minute) on dialysis and any platelet count: Initial dose: 5 mg once after dialysis; additional dose adjustments should be made with careful monitoring.
ESRD (CrCl <15 mL/minute) not requiring dialysis: Avoid use.
Graft-versus-host disease, chronic, treatment, refractory:
CrCl 15 to 59 mL/minute and any platelet count: Initial: 5 mg twice daily. Additional dose adjustments should be made with frequent monitoring.
End-stage renal disease (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.
Myelofibrosis:
CrCl 15 to 59 mL/minute and platelets >150,000/mm3: No dosage adjustment is necessary.
CrCl 15 to 59 mL/minute and platelets 100,000 to 150,000/mm3: Initial dose: 10 mg twice daily; additional dose adjustments should be made with careful monitoring.
CrCl 15 to 59 mL/minute and platelets 50,000 to <100,000/mm3: Initial dose: 5 mg once daily; additional dose adjustments should be made with careful monitoring.
CrCl 15 to 59 mL/minute and platelets <50,000/mm3: Avoid use.
ESRD (CrCl <15 mL/minute) on dialysis and platelets 100,000 to 200,000/mm3: Initial dose: 15 mg once after dialysis; administer subsequent doses after dialysis on dialysis days. Additional dose adjustments should be made with frequent monitoring.
ESRD (CrCl <15 mL/minute) on dialysis and platelets >200,000/mm3: Initial dose: 20 mg once after dialysis; administer subsequent doses after dialysis on dialysis days. Additional dose adjustments should be made with frequent monitoring.
ESRD not requiring dialysis: Avoid use.
Polycythemia vera:
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.
Hemodialysis is not expected to enhance the elimination of ruxolitinib.
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.
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.
|
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:
|
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:
|
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:
|
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):
|
Hematologic parameter |
Maximum restarting dose |
|---|---|
|
a Continue 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 dailya 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 dailya 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 dailya 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.
(For additional information see "Ruxolitinib (systemic): Pediatric drug information")
Graft-versus-host disease (GVHD), acute, steroid refractory, treatment:
Fixed dosing: 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-directed dosing: Children and Adolescents: Limited data available: Oral: Note: Dosing based on a retrospective study of 13 patients (aged 1.6 to 16.5 years) receiving ruxolitinib for steroid-refractory GVHD. Ruxolitinib was associated with a high incidence of reversible adverse effects and fair overall response rate (Ref).
<25 kg: 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: 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 (ie, 10 mg twice daily to 5 mg twice daily to 5 mg once daily). Consider retreatment if acute GVHD signs or symptoms recur during or after tapering ruxolitinib.
Graft-versus-host disease (GVHD), chronic, refractory, treatment:
Children ≥12 years and Adolescents: Oral: 10 mg twice daily; adjust as necessary for adverse effects (see "Dosing Adjustment for Toxicity").
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 (ie, 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosage adjustment for toxicity: Children ≥12 years and Adolescents: Oral:
Acute graft-versus-host disease:
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.
Chronic graft-versus-host disease:
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.
|
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. |
Children ≥12 years and Adolescents: Oral:
Graft-versus-host disease (GVHD); acute/steroid-refractory, treatment:
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 (GVHD); chronic, refractory, treatment
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.
Children ≥12 years and Adolescents: Oral:
Graft-versus-host disease (GVHD); acute/steroid-refractory, treatment:
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 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: Reduce dose to 5 mg once daily.
Hepatoxicity during treatment:
Total bilirubin elevation without liver GVHD:
Total bilirubin 3 to 5 times ULN: Reduce dose by 1 dose level until total bilirubin recovers.
Total bilirubin >5 to 10 times ULN: Interrupt ruxolitinib treatment for up to 14 days; when bilirubin recovers to ≤1.5 times ULN, may restart at current dose.
Total bilirubin >10 times ULN: Interrupt ruxolitinib treatment for up to 14 days; when bilirubin recovers to ≤1.5 times ULN, may restart at 1 dose level lower.
Total bilirubin elevation with liver GVHD: Total bilirubin >3 times ULN: Reduce dose 1 dose level until total bilirubin recovers.
Graft-versus-host disease (GVHD); chronic, refractory, treatment:
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 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 :
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.
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 (Verstovsek 2012)
Respiratory: Tuberculosis
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.
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 compensation, 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.
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
No
Tablets (Jakafi Oral)
5 mg (per each): $343.00
10 mg (per each): $343.00
15 mg (per each): $343.00
20 mg (per each): $343.00
25 mg (per each): $343.00
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.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Jakavi: 5 mg, 10 mg, 15 mg, 20 mg
Available through specialty/network pharmacies. Further information may be obtained from the manufacturer, Incyte, at 1-855-452-5234 or at www.Jakafi.com.
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).
Oral: Administer with or without food. May also administer through nasogastric (NG) tube (≥8 Fr) if unable to ingest tablets.
NG tube (≥8 Fr) administration: Suspend 1 tablet in ~40 mL water and stir for ~10 minutes; administer with appropriate syringe within 6 hours after dispersion; rinse NG tube with ~75 mL water (effect of enteral tube feedings [eg, enteral formulas] on ruxolitinib exposure has not been evaluated).
Missed dose: If a dose is missed, do not administer an additional dose; return to the usual dosing schedule.
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.
Ruxolitinib may be confused with cabozantinib, fedratinib, pacritinib, PONATinib, regorafenib, ripretinib, riTUXimab, rucaparib, tofacitinib.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP2C9 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Azithromycin (Systemic): May increase the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase serum concentrations of the active metabolite(s) of Ruxolitinib (Systemic). CYP3A4 Inducers (Strong) may decrease the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Ruxolitinib (Systemic). Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the 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 enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fluconazole: May increase the 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 the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect 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
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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 enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
Grapefruit juice may increase the effects of ruxolitinib. Management: Avoid grapefruit juice.
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).
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.
Avoid grapefruit juice (may increase the effects of ruxolitinib).
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), renal 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.
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.
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: Vd: 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.
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 renal 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.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
