Dosing & Uses
Dosage Forms & Strengths
tablet
- 5mg
- 10mg
- 15mg
- 20mg
- 25mg
Myelofibrosis
Kinase inhibitor indicated for treatment of patients with intermediate or high-risk myelofibrosis (MF), including primary MF, post-polycythemia vera MF and post-essential thrombocythemia MF
Initial dose
- Platelet count >200 x109/L: 20 mg PO BID
- Platelet count 100-200 x109/L: 15 mg PO BID
- Platelet count 50 to <100 x109/L: 5 mg PO BID
Insufficient response for patients starting treatment with a platelet count ≥100 X 10^9/L
- If response is insufficient and platelet count and ANC are adequate, dose may be increased in 5 mg BID increments; not to exceed 25 mg PO BID
- Do not increase dose during the first 4 weeks of therapy and no more frequently than q2Weeks
-
Consider dose increases in patients who meet all of the following conditions:
- Failure to achieve a reduction from pretreatment baseline in either palpable spleen length of 50% or a 35% reduction in spleen volume as measured by CT or MRI
- Platelet count >125 x109/L at 4 weeks and never <100 x109/L
- ANC levels >0.75 x109/L
- Long-term maintenance at 5 mg BID has not shown responses and limit continued use at this dose to patients in whom the benefits outweigh the potential risks
- Discontinue if there is no spleen size reduction or symptom improvement after 6 months of therapy
Insufficient response for patients starting treatment with a platelet count 50 x 10^9/L to <100 x 10^9/L
- If response is insufficient and platelet count and ANC are adequate, doses may be increased by increments of 5 mg qDay to up to 10 mg BID
- Do not increase dose during the first 4 weeks of therapy and no more frequently than q2Weeks
-
Consider dose increases in patients who meet all of the following conditions:
- Platelet count has remained at least 40 x 109/L
- Platelet count has not fallen by >20% in the prior 4 weeks
- ANC >1 x 109/L
- No dose reduction or interruption for an adverse event or hematological toxicity in the prior 4 weeks
- Continuation of treatment for >6 months should be limited to patients in whom the benefits outweigh the potential risks
- Discontinue treatment if there is no spleen size reduction or symptom improvement after 6 months of therapy
Polycythemia Vera
Indicated for polycythemia vera in patients who have had an inadequate response to or are intolerant of hydroxyurea
Initial: 10 mg PO BID
Increasing dose for insufficient response
- If response is insufficient and platelet, hemoglobin, and neutrophil counts are adequate, doses may be increased in 5 mg BID increments to a maximum of 25 mg BID
- Doses should not be increased during the first 4 weeks of therapy and not more frequently than q2Week
-
Consider dose increases in patients who meet all of the following criteria:
- Inadequate efficacy as demonstrated by ≥1 of the following: continued need for phlebotomy, WBC > ULN, platelet count >ULN, palpable spleen that is reduced by <25% from baseline
- Platelet count ≥140 x109/L
- Hemoglobin ≥2 g/dL
- ANC ≥1.5 x 109/L
Acute Graft versus Host Disease
Indicated for treatment of steroid-refractory acute graft-versus-host disease (GVHD)
Initial dose: 5 mg PO BID; may increase to 10 mg BID after at least 3 days if ANC and platelet counts have not decreased by ≥50% compared to baseline
Consider tapering after 6 months in patients with response who have discontinued therapeutic doses of corticosteroids
Tapering dose
- Taper by 1 dose level ~q8Weeks (eg, 10 mg BID to 5 mg BID to 5 mg qDay)
- Patients unable to tolerate 5 mg qDay: Interrupt treatment until clinical and/or laboratory parameters recover
- If acute GVHD signs or symptoms recur during or after taper, consider retreatment
Chronic Graft versus Host Disease
Indicated for treatment of chronic graft-versus-host disease (cGVHD) after failure of 1 or 2 lines of systemic therapy
Initial dose: 10 mg PO BID
Consider tapering after 6 months in patients with response who have discontinued therapeutic doses of corticosteroids
Tapering dose
- Taper by 1 dose level ~q8Weeks (eg, 10 mg BID to 5 mg BID, then from 5 mg BID to 5 mg qDay)
- If acute GVHD signs or symptoms recur during or after taper, consider retreatment
Dosage Modifications (MF)
Dosage modification for bleeding (regardless of platelet count)
- Interrupt treatment until bleeding resolved; consider resuming at prior dose if underlying cause of bleeding has resolved or at a reduced dose if underlying cause of bleeding persists
Treatment interruptions in patients starting treatment with a platelet count ≥100 x 10^9/L
- Interrupt treatment for platelet count <50 x 109/L or ANC <0.5 x 109/L
- After recovery of platelet counts >50 x 109/L and ANC >0.75 X 109/L, restart dose
-
Restart doses after interruption are as follows
- Restart dose at least 5 mg BID below the dose at interruption; maximum doses listed below
- Platelet count ≥125 x109/L: 20 mg BID
- Platelet count 100 to <125 x109/L: 15 mg BID
- Platelet count 75 to <100 x109/L: 10 mg BID for at least 2 weeks; if stable, may increase to 15 mg BID
- Platelet count 50 to <75 x109/L: 5 mg BID for at least 2 weeks; if stable, may increase to 10 mg BID
- Platelet count <50 x109/L: Continue to hold dose
- After ANC recovers to ≥0.75 X 109/L, restart at the higher of 5 mg qDay or 5 mg BID below the largest dose in the week before treatment interruption
-
Dosage modifications for thrombocytopenia
- Platelet count 100 to <125 x109/L: if taking 25 mg BID, decrease to 20 mg BID; if taking 20 mg BID, decrease to 15 mg BID; do not change dose if taking lower doses
- Platelet count 75 to <100 x109/L: 10 mg BID; do not change dose if taking 5 mg BID
- Platelet count 50 to <75 x109/L: 5 mg BID
- Platelet count <50 x109/L: Hold dose
- Long-term maintenance at a 5 mg BID dose has not shown responses and continued use at this dose should be limited to patients in whom the benefits outweigh the potential risks
Treatment interruption in patients starting treatment with a platelet count 50 to <75 x10^9/L
- Interrupt treatment for platelet count <25 x 109/L or ANC less than 0.5 X 109/L
- After recovery of platelet count >35 X 109/L and ANC >0.75 X 109/L, dosing may be restarted
- Restart at the higher of 5 mg qDay or 5 mg BID below the largest dose in the week before treatment interruption
-
Dosage modifications for thrombocytopenia
- Platelet count<25 x 109/L: Interrupt dose
- Platelet count 25 x 109/L to <35 X 109/L AND the decrease in platelet count is <20% during the prior 4 weeks: Decrease dose by 5 mg qDay; for patients on 5 mg qDay, maintain current dose
- Platelet count 25 x 109/L to <35 X 109/L AND the decrease in platelet count is ≥20%during the prior 4 weeks: Decrease dose by 5 mg BID; for patients on 5 mg BID, decrease dose to 5 mg qDay; for patients on 5 mg qDay, maintain current dose
Renal impairment
-
Moderate-to-severe (CrCl 15-59 mL/min)
- Platelet count >150 x109/L: No dosage adjustment necessary
- Platelet count 100-150 x109/L: Starting dose is 10 mg BID
- Platelet count 50 to <100 x109/L: Starting dose is 5 mg qDay
- Platelet count <50 x109/L: Avoid use
-
ESRD (CrCl <15 mL/min)
- On dialysis and platelet count 100-200 x109/L: 15 mg once following dialysis session
- On dialysis and platelet count >200 x109/L: 20 mg once following dialysis session
- Not on dialysis: Avoid use
Hepatic impairment (any severity)
- Platelet count >150 x109/L: No dosage adjustment necessary
- Platelet count 100-150 x109/L: Starting dose is 10 mg BID
- Platelet count 50 to <100 x109/L: Starting dose is 5 mg qDay
- Platelet count <50 x109/L: Avoid use
Coadministration with strong CYP3A4 inhibitors or fluconazole
- Reduce dose when coadministered with strong CYP3A4 inhibitors or fluconazole (≤200 mg/day)
- Avoid fluconazole doses >200 mg/day concomitantly with ruxolitinib
- Closely monitor blood cell counts for toxicity and adjust ruxolitinib dose if necessary when coadministered with itraconazole
-
Starting dose for patients with myelofibrosis based on platelet count
- Platelet count ≥100 x 109/L: 10 mg BID
- Platelet counts 50 to <100 x 109/L: 5 mg BID
- If stable on 10 mg BID, reduce by 50% (round up to the closest available tablet strength)
- If stable on 5 mg BID, reduce 5 mg qDay
- If stable on 5 mg qDay, avoid strong CYP3A4 inhibitor or fluconazole treatment or interrupt ruxolitinib for the duration of strong CYP3A4 inhibitor or fluconazole use
Coadministration with CYP3A4 inducers
- No dose adjustment recommended; however, closely monitor and titrate dose based on safety and efficacy
Dosage Modifications (PV)
Dose reductions
- Hgb ≥12 g/dL AND platelet count ≥100 x109/L: No change required
- Hgb 10 to <12 g/dL AND platelet count 75 to <100 x109/L: Consider dose reduction with the goal of avoiding dose interruptions for anemia and thrombocytopenia
- Hgb 8 to <10 g/dL OR platelet count 50 to <75 x109/L: Reduce dose by 5 mg BID; if already on 5 mg BID, then reduce dose to 5 mg qDay
- Hgb <8 g/dL OR platelet count <50 x109/L: Interrupt dosing
Treatment interruption and restarting dosing
- Interrupt treatment for hgb <8 g/dL, platelet counts <50 x109/L, or ANC <1 x109/L
- After recovery to acceptable levels, dosing may be restarted
-
Use most severe category for individual parameters
- Hgb <8 g/dL OR platelet count <50 x109/L OR ANC <1 x109/L: Continue to hold dosing
- Hgb 8 to <10 g/dL OR platelet count 50 to <75 x109/L OR ANC 1 to <1.5 x109/L: 5 mg BID, or not to exceed 5 mg BID less than the dose which resulted in dose interruption
- Hgb 10 to <12 g/dL OR platelet count 75 to <100 x109/L OR ANC 1.5 to <2 x10^9/L: 10 mg BID or not to exceed 5 mg BID less than the dose which resulted in dose interruption
- Hgb ≥12 g/dL OR platelet count ≥100 x 10^9/L OR ANC ≥2 x10^9/L: 15 mg BID or not to exceed 5 mg BID less than the dose which resulted in dose interruption
- Reinitiated doses: Continue dose for at least 2 weeks; if stable, may increase dose 5 mg BID
- Patients receiving a dose of 5 mg BID and required dose interruption, may restart at 5 mg BID or 5 mg qDay, but not higher, once hemoglobin ≥10 g/dL, platelet count ≥75 x 10^9/L, and ANC ≥1.5 x 109/L
Renal impairment
- Moderate-to-severe (CrCl 15-59 mL/min) with any platelet count: Starting dose is 5 mg BID
- ESRD (CrCl <15 mL/min) on dialysis: 10 mg once after dialysis session
- ESRD (CrCl <15 mL/min) not on dialysis: Avoid use
Hepatic impairment
- Mild, moderate, or severe (Child-Pugh A, B, C) with any platelet count: Starting dose is 5 mg BID
Concomitant use with strong CYP3A4 inhibitors
- Dose reductions for patients with PV on concomitant strong CYP3A4 inhibitors or fluconazole doses ≤200 mg
- Avoid fluconazole doses >200 mg/day concomitantly with ruxolitinib
- Closely monitor blood cell counts for toxicity and adjust ruxolitinib dose if necessary when coadministered with itraconazole
-
Starting dose for patients with PV
- Stable on ≥10 mg BID: Reduce dose by 50% (rounded up to the closest available tablet strength)
- Stable on 5 mg BID: Reduce to 5 mg qDay
- Stable on 5 mg PO qDay: Avoid coadministration with strong CYP3A4 inhibitors or fluconazole treatment or interrupt ruxolitinib treatment for the duration of strong CYP3A4 inhibitor or fluconazole use
Coadministration with CYP3A4 inducers
- No dose adjustment recommended; however, closely monitor and titrate dose based on safety and efficacy
Dose Modifications (Acute GVHD)
Taper by 1 dose level (eg, 10 mg BID to 5 mg BID to 5 mg qDay)
Clinically significant thrombocytopenia after supportive measures: Reduce dose by 1 dose level; when platelets recover to previous values, restart dose to prior dose level
ANC <1 X 109/L (dose-related): Hold dose for up to 14 days; resume at 1 dose level lower upon recovery
Total bilirubin elevation, no liver GVHD
- Total bilirubin 3 to 5x ULN: Continue at 1 dose level lower until recovery
- Total bilirubin >5 to10x ULN: Hold dose for up to 14 days until bilirubin ≤1.5x ULN; resume at current dose upon recovery
- Total bilirubin >10x ULN: Hold dose for up to 14 days until bilirubin ≤1.5x ULN; resume at 1 dose level lower upon recovery
Total bilirubin elevation with liver GVHD
- Total bilirubin >3x ULN: Continue at 1 dose level lower until recovery
Renal impairment
- Moderate or severe (CrCl 15-59 mL/min): Reduce dose to 5 mg qDay
- ESRD (CrCl <15 mL/min) on dialysis: 5 mg once after dialysis session
Hepatic impairment
- Mild, moderate, or severe (Child-Pugh A, B, C) with any platelet count: No dosage adjustment necessary
- Stage 3 or 4 GvHD: Monitor blood cell counts more frequently for toxicity and consider 5 mg qDay
Concomitant use with strong CYP3A4 inhibitors
- Dose reductions for patients with acute GvHD on concomitant strong CYP3A4 inhibitors or fluconazole doses of ≤200 mg
- Avoid fluconazole doses >200 mg/day concomitantly with ruxolitinib
- Coadministered with other strong CYP3A4 inhibitors: Closely monitor blood cell counts for toxicity and adjust ruxolitinib dose if necessary
Coadministration with CYP3A4 inducers
- No dose adjustment recommended; however, closely monitor and titrate dose based on safety and efficacy
Dose Modifications (Chronic GVHD)
Dose reduction schedule
- Currently taking 10 mg BID: Reduce to 5 mg BID
- Currently taking 5 mg BID: Reduce to 5 mg qDay
- Currently taking 5 mg qDay: Interrupt dosing until clinical and/or laboratory parameters recover
Thrombocytopenia
- Platelets <20 x 109/L: Reduce dose by 1 dose level
- If resolved within 7 days, return to initial dose level
- If not resolved within 7 days, maintain at 1 dose level lower
Decreased neutrophils
- ANC considered related to ruxolitinib
- ANC <0.75 x 109/L: Reduce dose by 1 level; resume at initial dose level upon recovery
- ANC <0.5 x 109/L: Hold dose for up to 14 days; resume at 1 dose level lower upon recovery; may resume initial dose level when ANC >1 x 109/L
Total bilirubin elevation
-
Total bilirubin 3 to 5x ULN
- Continue 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 at decreased dose level
-
Total bilirubin >5 to 10x ULN
- Hold dose for up to 14 days until resolved; resume at current dose upon recovery
- If not resolved within 14 days, resume at 1 dose level lower upon recovery
-
Total bilirubin >10x ULN
- Hold dose for up to 14 days until resolved; resume at current dose upon recovery
- Discontinue if not resolved within 14 days
Other adverse reactions
- Grade 3: Continue at 1 dose level lower until recovery
- Grade 4: Discontinue
Renal impairment
- Moderate or severe (CrCl 15-59 mL/min): Reduce dose to 5 mg BID
- ESRD (CrCl <15 mL/min) on dialysis: 10 mg once after dialysis session
Hepatic impairment
- Mild, moderate, or severe (Child-Pugh A, B, C) without liver GVHD: No dosage adjustment necessary
- Score 1 or 2 liver cGVHD: No dosage adjustment necessary
- Score 3 liver cGVHD: Monitor blood cell counts more frequently for toxicity and modify dose if adverse reactions occur
Concomitant use with strong CYP3A4 inhibitors
- Fluconazole doses ≤200 mg: Reduce to 5 mg BID
- Avoid fluconazole doses >200 mg/day concomitantly with ruxolitinib
- Coadministered with other CYP3A4 inhibitors: Monitor blood cell counts more frequently for toxicity and modify dosage for adverse reactions if they occur
Coadministration with CYP3A4 inducers
- No dose adjustment recommended; however, closely monitor and titrate dose based on safety and efficacy
Dosing Considerations
Perform complete blood cell count (CBC) and platelet count before initiating therapy, q2-4Weeks until doses are stabilized, and then as clinically indicated
Orphan Designations
Pancreatic cancer
Orphan sponsor
- Incyte Corporation; 1801 Augustine Cut-Off; Wilmington, Delaware 19803
Dosage Forms & Strengths
tablet
- 5mg
- 10mg
- 15mg
- 20mg
- 25mg
Acute Graft versus Host Disease
Indicated for treatment of steroid-refractory acute graft-versus-host disease (GVHD) in adults and children (≥12 years)
<12 years: Safety and efficacy not established
≥12 years
- Initial dose: 5 mg PO BID; may increase to 10 mg BID after at least 3 days if ANC and platelet counts have not decreased by ≥50% compared to baseline
- Consider tapering after 6 months of treatment in patients with response who have discontinued therapeutic doses of corticosteroids
-
Tapering dose
- Taper by 1 dose level ~q8Weeks (eg, 10 mg BID to 5 mg BID to 5 mg qDay)
- Patients unable to tolerate 5 mg qDay: Interrupt treatment until clinical and/or laboratory parameters recover
- If acute GVHD signs or symptoms recur during or after taper, consider retreatment
Chronic Graft versus Host Disease
Indicated for treatment of chronic graft-versus-host disease (cGVHD) after failure of 1 or 2 lines of systemic therapy in adolescents aged ≥12 years
<12 years: Safety and efficacy not established
≥12 years
- Initial dose: 10 mg PO BID
- Consider tapering after 6 months in patients with response who have discontinued therapeutic doses of corticosteroids
-
Tapering dose
- Taper by 1 dose level ~q8Weeks (eg, 10 mg BID to 5 mg BID, then from 5 mg BID to 5 mg qDay)
- If acute GVHD signs or symptoms recur during or after taper, consider retreatment
Dose Modifications (Acute GVHD)
Clinically significant thrombocytopenia after supportive measures: Reduce dose by 1 dose level; when platelets recover to previous values, restart dose to prior dose level
ANC <1 X 109/L (dose-related): Hold dose for up to 14 days; resume at 1 dose level lower upon recovery
Total bilirubin elevation, no liver GVHD
- Total bilirubin 3 to 5x ULN: Continue at 1 dose level lower until recovery
- Total bilirubin >5 to10x ULN: Hold dose for up to 14 days until bilirubin ≤1.5x ULN; resume at current dose upon recovery
- Total bilirubin >10x ULN: Hold dose for up to 14 days until bilirubin ≤1.5x ULN; resume at 1 dose level lower upon recovery
Total bilirubin elevation with liver GVHD
- Total bilirubin >3x ULN: Continue at 1 dose level lower until recovery
Renal impairment
- Moderate or severe (CrCl 15-59 mL/min): Reduce dose to 5 mg qDay
- ESRD (CrCl <15 mL/min) on dialysis: 5 mg once after dialysis session
Hepatic impairment
- Mild, moderate, or severe (Child-Pugh A, B, C) with any platelet count: No dosage adjustment necessary
- Stage 3 or 4 GvHD: Monitor blood cell counts more frequently for toxicity and consider 5 mg qDay
Concomitant use with strong CYP3A4 inhibitors
- Dose reductions for patients with acute GvHD on concomitant strong CYP3A4 inhibitors or fluconazole doses of ≤200 mg
- Avoid fluconazole doses >200 mg/day concomitantly with ruxolitinib
- Coadministered with other strong CYP3A4 inhibitors: Closely monitor blood cell counts for toxicity and adjust ruxolitinib dose if necessary
Coadministration with CYP3A4 inducers
- No dose adjustment recommended; however, closely monitor and titrate dose based on safety and efficacy
Dose Modifications (Chronic GVHD)
Dose reduction schedule
- Currently taking 10 mg BID: Reduce to 5 mg BID
- Currently taking 5 mg BID: Reduce to 5 mg qDay
- Currently taking 5 mg qDay: Interrupt dosing until clinical and/or laboratory parameters recover
Thrombocytopenia
- Platelets <20 x 109/L: Reduce dose by 1 dose level
- If resolved within 7 days, return to initial dose level
- If not resolved within 7 days, maintain at 1 dose level lower
Decreased neutrophils
- ANC considered related to ruxolitinib
- ANC <0.75 x 109/L: Reduce dose by 1 level; resume at initial dose level upon recovery
- ANC <0.5 x 109/L: Hold dose for up to 14 days; resume at 1 dose level lower upon recovery; may resume initial dose level when ANC >1 x 109/L
Total bilirubin elevation
-
Total bilirubin 3 to 5x ULN
- Continue 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 at decreased dose level
-
Total bilirubin >5 to 10x ULN
- Hold dose for up to 14 days until resolved; resume at current dose upon recovery
- If not resolved within 14 days, resume at 1 dose level lower upon recovery
-
Total bilirubin >10x ULN
- Hold dose for up to 14 days until resolved; resume at current dose upon recovery
- Discontinue if not resolved within 14 days
Other adverse reactions
- Grade 3: Continue at 1 dose level lower until recovery
- Grade 4: Discontinue
Renal impairment
- Moderate or severe (CrCl 15-59 mL/min): Reduce dose to 5 mg BID
- ESRD (CrCl <15 mL/min) on dialysis: 10 mg once after dialysis session
Hepatic impairment
- Mild, moderate, or severe (Child-Pugh A, B, C) without liver GVHD: No dosage adjustment necessary
- Score 1 or 2 liver cGVHD: No dosage adjustment necessary
- Score 3 liver cGVHD: Monitor blood cell counts more frequently for toxicity and modify dose if adverse reactions occur
Concomitant use with strong CYP3A4 inhibitors
- Fluconazole doses ≤200 mg: Reduce to 5 mg BID
- Avoid fluconazole doses >200 mg/day concomitantly with ruxolitinib
- Coadministered with other CYP3A4 inhibitors: Monitor blood cell counts more frequently for toxicity and modify dosage for adverse reactions if they occur
Coadministration with CYP3A4 inducers
- No dose adjustment recommended; however, closely monitor and titrate dose based on safety and efficacy
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (36)
- abametapir
abametapir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.
- apalutamide
apalutamide will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.
- atazanavir
atazanavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- ceritinib
ceritinib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- chloramphenicol
chloramphenicol will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib dosage during coadministration with chloramphenicol in patients with myelofibrosis (MF) or polycythemia vera (PV); no dose adjustments necessary for patients with graft-versus-host disease
- clarithromycin
clarithromycin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- cobicistat
cobicistat will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- conivaptan
conivaptan will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- darunavir
darunavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- deferiprone
deferiprone, ruxolitinib. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis; if an alternative is not possible, monitor absolute neutrophil count more frequently.
- fexinidazole
fexinidazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.
- fosamprenavir
fosamprenavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- grapefruit
grapefruit will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- idelalisib
idelalisib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Idelalisib is a strong CYP3A inhibitor; avoid coadministration with sensitive CYP3A substrates
- imatinib
imatinib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- indinavir
indinavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- isoniazid
isoniazid will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- itraconazole
itraconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- ivosidenib
ivosidenib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternative therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.
- ketoconazole
ketoconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If starting ruxolitinib and currently treated with strong CYP3A4 inhibitors, start ruxolitinib at 5 mg BID in polycythemia vera. In myelofibrosis patients, start ruxolitinib at 10 mg BID in those with platelet counts 100 x10^9/L or greater, or 5 mg qDay in those with platelet counts at 50 to 100 x 10^9/L. In patients currently on ruxolitinib and starting a CYP3A4 inhibitor, reduce ruxolitinib dose by 50% (ie, 10 mg BID to 5 mg BID). Avoid strong CYP3A4 inhibitors in patients currently treated with ruxolitinib 5 mg qDay.
- levoketoconazole
levoketoconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If starting ruxolitinib and currently treated with strong CYP3A4 inhibitors, start ruxolitinib at 5 mg BID in polycythemia vera. In myelofibrosis patients, start ruxolitinib at 10 mg BID in those with platelet counts 100 x10^9/L or greater, or 5 mg qDay in those with platelet counts at 50 to 100 x 10^9/L. In patients currently on ruxolitinib and starting a CYP3A4 inhibitor, reduce ruxolitinib dose by 50% (ie, 10 mg BID to 5 mg BID). Avoid strong CYP3A4 inhibitors in patients currently treated with ruxolitinib 5 mg qDay.
- lonafarnib
lonafarnib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration with sensitive CYP3A substrates. If coadministration unavoidable, monitor for adverse reactions and reduce CYP3A substrate dose in accordance with product labeling.
- lopinavir
lopinavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- nefazodone
nefazodone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- nelfinavir
nelfinavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- nicardipine
nicardipine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- palifermin
palifermin increases toxicity of ruxolitinib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hrbefore, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.
- posaconazole
posaconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- quinidine
quinidine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- ritonavir
ritonavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- ropeginterferon alfa 2b
ropeginterferon alfa 2b, ruxolitinib. Either increases toxicity of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Myelosuppressive agents can produce additive myelosuppression. Avoid use and monitor patients receiving the combination for effects of excessive myelosuppression.
- saquinavir
saquinavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- tipranavir
tipranavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- tucatinib
tucatinib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.
- voriconazole
voriconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Reduce ruxolitinib starting dose to 10 mg BID with platelet count 100 X 10^9/L or more and concurrent use of strong CYP3A4 inhibitors; avoid with platelet counts <100 X 10^9/L
- voxelotor
voxelotor will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.
Monitor Closely (55)
- amiodarone
amiodarone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- aprepitant
aprepitant will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bicalutamide
bicalutamide will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- bosentan
bosentan will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- carbamazepine
carbamazepine will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- cenobamate
cenobamate will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.
- cholera vaccine
ruxolitinib decreases effects of cholera vaccine by immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Immunosuppressive therapies, including irradiation, antimetabolites, alkylating agents, cytotoxic drugs and corticosteroids (used in greater than physiologic doses), may reduce the immune response to cholera vaccine.
- cimetidine
cimetidine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- clotrimazole
clotrimazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- crofelemer
crofelemer increases levels of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Crofelemer has the potential to inhibit CYP3A4 at concentrations expected in the gut; unlikely to inhibit systemically because minimally absorbed.
- cyclosporine
cyclosporine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dabrafenib
dabrafenib will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
- diltiazem
diltiazem will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- doxycycline
doxycycline will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- dronedarone
dronedarone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- duvelisib
duvelisib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.
- efavirenz
efavirenz will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- elagolix
elagolix decreases levels of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP3A4 inhibitor; contraindicated with CYP3A4 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.
- encorafenib
encorafenib, ruxolitinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.
- enzalutamide
enzalutamide will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin base
erythromycin base will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fedratinib
fedratinib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.
- fluconazole
fluconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosaprepitant
fosaprepitant will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- fosphenytoin
fosphenytoin will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- haloperidol
haloperidol will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- iloperidone
iloperidone increases levels of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.
- istradefylline
istradefylline will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.
- lapatinib
lapatinib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- lenacapavir
lenacapavir will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- lidocaine
lidocaine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- metronidazole
metronidazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- mitotane
mitotane decreases levels of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.
- nafcillin
nafcillin will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- ofatumumab SC
ofatumumab SC, ruxolitinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Consider the risk of additive immune system effects when coadministering immunosuppressive therapies with coadministration. When switching from therapies with immune effects, take into account the duration and mechanism of action of these therapies when initiating ofatumumab SC.
- phenobarbital
phenobarbital will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- phenytoin
phenytoin will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- primidone
primidone will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rifapentine
rifapentine will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- rucaparib
rucaparib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.
- sertraline
sertraline will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- siponimod
siponimod and ruxolitinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- stiripentol
stiripentol, ruxolitinib. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.
- tazemetostat
tazemetostat will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- tecovirimat
tecovirimat will decrease the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.
- tetracycline
tetracycline will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- trastuzumab
trastuzumab, ruxolitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.
- trastuzumab deruxtecan
trastuzumab deruxtecan, ruxolitinib. Either increases toxicity of the other by immunosuppressive effects; risk of infection. Use Caution/Monitor. Neutropenia or febrile neutropenia incidence were increased when trastuzumab was coadministered with myelosuppressive chemotherapy.
- ublituximab
ublituximab and ruxolitinib both increase immunosuppressive effects; risk of infection. Modify Therapy/Monitor Closely. Owing to potential additive immunosuppressive effects, consider duration of effect and mechanism of action of these therapies if coadministered
- verapamil
verapamil will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
Minor (100)
- acetaminophen
acetaminophen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- acetaminophen IV
acetaminophen IV will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- acetaminophen rectal
acetaminophen rectal will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- acetazolamide
acetazolamide will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- amlodipine
amlodipine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- armodafinil
armodafinil will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- atorvastatin
atorvastatin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- azelastine
azelastine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- azithromycin
azithromycin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- betamethasone
betamethasone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- bortezomib
bortezomib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- bromocriptine
bromocriptine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- chlorzoxazone
chlorzoxazone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ciprofloxacin
ciprofloxacin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- clemastine
clemastine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cocaine topical
cocaine topical will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- danazol
danazol will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- darifenacin
darifenacin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dasatinib
dasatinib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- desvenlafaxine
desvenlafaxine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dexmedetomidine
dexmedetomidine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- diazepam
diazepam will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- diclofenac
diclofenac will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dihydroergotamine
dihydroergotamine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- dihydroergotamine intranasal
dihydroergotamine intranasal will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- disulfiram
disulfiram will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- docetaxel
docetaxel will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- doxorubicin
doxorubicin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- doxorubicin liposomal
doxorubicin liposomal will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- drospirenone
drospirenone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ergotamine
ergotamine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ethinylestradiol
ethinylestradiol will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- etoposide
etoposide will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- felodipine
felodipine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fluoxetine
fluoxetine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- fluvastatin
fluvastatin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- glyburide
glyburide will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- hydralazine
hydralazine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ifosfamide
ifosfamide will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- irbesartan
irbesartan will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- isradipine
isradipine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- losartan
losartan will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lovastatin
lovastatin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- lurasidone
lurasidone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- mefloquine
mefloquine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- mestranol
mestranol will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- methadone
methadone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- methimazole
methimazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- methoxsalen
methoxsalen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- methylprednisolone
methylprednisolone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- micafungin
micafungin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- midazolam
midazolam will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- mifepristone
mifepristone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- mirtazapine
mirtazapine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- mitoxantrone
mitoxantrone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nevirapine
nevirapine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nifedipine
nifedipine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- nisoldipine
nisoldipine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- olanzapine
olanzapine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- omeprazole
omeprazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- orphenadrine
orphenadrine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- oxybutynin
oxybutynin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- oxybutynin topical
oxybutynin topical will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- oxybutynin transdermal
oxybutynin transdermal will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- paroxetine
paroxetine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pazopanib
pazopanib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pentamidine
pentamidine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pilocarpine
pilocarpine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pimozide
pimozide will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- pravastatin
pravastatin will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- primaquine
primaquine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- progesterone micronized
progesterone micronized will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- progesterone, natural
progesterone, natural will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- propofol
propofol will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- quinine
quinine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ranolazine
ranolazine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ribociclib
ribociclib will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- risperidone
risperidone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- selegiline
selegiline will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sirolimus
sirolimus will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- sulconazole
sulconazole will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- tamoxifen
tamoxifen will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- temsirolimus
temsirolimus will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- teniposide
teniposide will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- testosterone
testosterone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- testosterone buccal system
testosterone buccal system will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- testosterone topical
testosterone topical will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ticlopidine
ticlopidine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- tranylcypromine
tranylcypromine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- trazodone
trazodone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- valproic acid
valproic acid will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- vinblastine
vinblastine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- vincristine
vincristine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- vincristine liposomal
vincristine liposomal will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- vinorelbine
vinorelbine will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- zafirlukast
zafirlukast will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- ziprasidone
ziprasidone will increase the level or effect of ruxolitinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
Adverse Effects
>10% (MF and PV)
Anemia (96.1%)
Thrombocytopenia (69.7%)
Increased ALT, grade 1 (25.2%)
Bruising (23.2%)
Neutropenia (18.7%)
Dizziness (18.1%)
Increased AST, grade 1 (17.1%)
Increased cholesterol, grade 1 (16.8%)
Headache (14.8%)
>10% (GvHD)
Anemia (75%)
Thrombocytopenia (75%)
Thrombocytopenia, Grade 3-4 (61%)
Neutropenia (58%)
Infections (55%)
Edema (51%)
Hemorrhage (49%)
Anemia, Grade 3-4 (45%)
Infections, Grade 3-4 (41%)
Neutropenia (40%)
Elevated ALT/AST (48%)
Fatigue (37%)
Bacterial infections (32%)
Bacterial infections, Grade 3-4 (28%)
Hemorrhage, Grade 3-4 (20%)
Fatigue, Grade 3-4 (14%)
Edema, Grade 3-4 (13%)
Hypertriglyceridemia (11%)
1-10% (MF and PV)
Urinary tract infection (9%)
Weight gain (7.1%)
Flatulence (5.2%)
Herpes zoster (1.9%)
Increased ALT, grade 2 (1.9%)
Increased ALT, grade 3 (1.3%)
1-10% (GvHD)
Elevated ALT/AST, Grade 3-4 (6-8%)
Hypertriglyceridemia, Grade 3-4 (1%)
<1%
Increased AST, grade 2 (0.6%)
Increased cholesterol, grade 2 (0.6%)
Postmarketing Reports
Infections and infestations: Herpes simplex virus reactivation and/or dissemination
Warnings
Contraindications
None
Cautions
Nonmelanoma skin cancers reporrted including basal cell, squamous cell, and Merkel cell carcinoma
Thrombocytopenia, anemia, & neutropenia
- Perform CBC before initiating therapy and monitor as clinically indicated and dosing adjusted as required
- Patients with platelet counts <200 x109/L at the start of therapy are more likely to develop thrombocytopenia during treatment
- Thrombocytopenia was generally reversible and was usually managed by reducing the dose or temporarily withholding dose (see Adult Dosing); if clinically indicated, platelet transfusions may be administered
- Anemia may require blood transfusions; dose modifications may also be considered
- Neutropenia (ANC <0.5 x109/L) was generally reversible and was managed by temporarily withholding dose
Infections
- Assess for the risk of developing serious bacterial, mycobacterial, fungal, and viral infections
- Active serious infections should have resolved before starting therapy
- Tuberculosis (TB) infection has been reported; before initiating, evaluate patients for TB risk factors, and those at higher risk should be tested for latent infection; risk factors include, but are not limited to, prior residence in or travel to countries with a high prevalence of tuberculosis, close contact with a person with active tuberculosis, and a history of active or latent tuberculosis where an adequate course of treatment cannot be confirmed; the decision to continue therapy during treatment of active tuberculosis should be based on overall risk-benefit determination
- Carefully observe patients for signs and symptoms of infection and initiate appropriate treatment promptly
- Herpes zoster: Inform patients about early signs and symptoms of herpes zoster and advise to seek treatment as early as possible
- Herpes simplex: Virus reactivation and/or dissemination reported in patients receiving therapy; monitor patients for development of herpes simplex infections; if a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment; patients should be promptly treated and monitored according to clinical guidelines
- Progressive multifocal leukoencephalopathy (PML): Reported with ruxolitinib treatment for myelofibrosis; if suspected, discontinue drug and evaluate
- Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, reported in patients with chronic HBV infection; effect of ruxolitinib on viral replication unknown; treat and monitor patients with chronic HBV infection according to clinical guidelines
Symptoms with dose interruption, dose tapering, or discontinuing
- Following discontinuation/interruption, myelofibrosis symptoms may be exacerbated and general return to pretreatment levels after 1 week
- Other adverse effects reported include fever, respiratory distress, hypotension, DIC, or multiorgan failure
- If these symptoms occur after discontinuation or dose tapering, evaluate and treat any intercurrent illness and consider restarting ruxolitinib or increase the dose
- Instruct patients not to interrupt or discontinue ruxolitinib without consulting their physician
- When discontinuing or interrupting therapy for reasons other than thrombocytopenia or neutropenia, consider tapering the dose gradually rather than discontinuing abruptly
Hyperlipidemia
- Treatment has been associated with increases in lipid parameters including total cholesterol, low density lipoprotein, and triglycerides; assess lipid parameters approximately 8-12 weeks following initiation of therapy; monitor according to clinical guidelines for management of hyperlipidemia
Major adverse cardiovascular events (MACE)
- Increased risk of MACE reported with another JAK inhibitor, including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which this drug is not indicated
- Consider benefits and risks for individual patient prior to initiating or continuing therapy, particularly in patients who are current or past smokers and patients with other cardiovascular risk factors; patients should be informed about symptoms of serious cardiovascular events and steps to take if they occur
Thrombosis
- Another JAK-inhibitor has increased risk of thrombosis, including deep venous thrombosis (DVT), pulmonary embolism (PE), and arterial thrombosis (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which this drug is not indicated
- In patients with MF and PV treated with this drug in clinical trials, the rates of thromboembolic events were similar in treated and control treated patients.
- Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately
Secondary malignancies
- Another JAK-inhibitor has increased risk of lymphoma and other malignancies excluding NMSC (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated; patients who are current or past smokers are at additional increased risk
- Consider benefits and risks for individual patient prior to initiating or continuing therapy, particularly in patients with a known secondary malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and patients who are current or past smokers
Drug interactions overview
-
CYP3A4 inhibitors
- Ruxolitinib is predominantly metabolized by CYP3A4
- Strong CYP3A4 inhibitors increase ruxolitinib Cmax and AUC 33% and 91%, respectively
- Dose modification recommended when coadministered with strong CYP3A4 inhibitors (such as but not limited to boceprevir, clarithromycin, conivaptan, grapefruit juice, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, nefazodone, nelfinavir, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole)
-
CYP3A4 inducers
- Coadministration with strong CYP3A4 inducers may decrease ruxolitinib exposure
Pregnancy & Lactation
Pregnancy
When pregnant rats and rabbits were administered ruxolitinib during organogenesis adverse developmental outcomes occurred at doses associated with maternal toxicity
There are no studies with use in pregnant women to inform drug-associated risks
Lactation
No data are available regarding the presence of ruxolitinib in human milk, the effects on the breast fed child, or the effects on milk production
Ruxolitinib and/or its metabolites were present in the milk of lactating rats
Because many drugs are present in human milk and because of the potential for thrombocytopenia and anemia shown for ruxolitinib in human studies, discontinue breastfeeding during treatment and for 2 weeks after final dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Kinase inhibitor; inhibits Janus Associated Kinases (JAKs) JAK1 and JAK2 which mediate the signaling of a number of cytokines and growth factors that are important for hematopoiesis and immune function
JAK signaling involves recruitment of STATs (signal transducers and activators of transcription) to cytokine receptors, activation and subsequent localization of STATs to the nucleus leading to modulation of gene expression
Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) known to be associated with dysregulated JAK1 and JAK2 signaling
Absorption
Bioavailability: 95%
Peak plasma time: 1-2 hr
Distribution
Protein bound: 97% (mostly albumin)
Vd at steady-state: 72 L (MF); 75 L (PV)
Metabolism
Ruxolitinib is the predominant entity in humans representing approximately 60% of the drug-related material in circulation
Metabolized by CYP3A4 (major)
Metabolites: 2 major active metabolites identified representing 25% and 11% of parent AUC; these 2 metabolites have 20% and 50% of ruxolitinib’s pharmacological activity, respectively; the sum total of all active metabolites contributes 18% of the overall pharmacodynamics of ruxolitinib
Elimination
Half-life: 2.8- 3 hr (ruxolitinib); 5.8 hr (ruxolitinib plus metabolites); 5 hr (hepatic impairment)
Clearance: 17.7 L/hr (women, MF); 22.1 L/hr (males, MF); 12.7 L/hr (PV); 11.9 L/hr (acute GvHD)
Excretion: feces (22%), urine (74%); unchanged drug accounted for <1%
Administration
Oral Administration
Take with or without food
If a dose is missed, patients do not take an additional dose, but take the next usual prescribed dose
When discontinuing for reasons other than thrombocytopenia, consider gradual tapering the dose (eg, by 5 mg q12hr per week)
NG tube administration
If unable to ingest tablets, can be administered through a nasogastric tube (8 French or greater) as follows
- Suspend 1 tablet in ~40 mL of water with stirring for ~10 minutes
- Administer suspension within 6 hr after the tablet has dispersed through NG using an appropriate syringe
- Rinse NG tube with ~75 mL of water
- Effect of tube feeding preparations on ruxolitinib exposure during administration through NG has not been evaluated
Storage
Tablet: Store at room temperature 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
Suspension for NG tube: Store at room temperature 20-25°C (68-77°F) for up to 6 hr
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Jakafi oral - | 25 mg tablet |  | |
| Jakafi oral - | 20 mg tablet |  | |
| Jakafi oral - | 10 mg tablet |  | |
| Jakafi oral - | 15 mg tablet |  | |
| Jakafi oral - | 5 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
ruxolitinib oral
RUXOLITINIB - ORAL
(RUX-oh-LI-ti-nib)
COMMON BRAND NAME(S): Jakafi
USES: This medication is used to treat certain bone marrow disorders (myelofibrosis, polycythemia vera). It works by blocking your body from producing substances called growth factors. Growth factors cause cells to grow and divide, and cause the blood cell and spleen problems found in these disorders. Ruxolitinib belongs to a class of drugs known as kinase inhibitors. Though not a cure for these disorders, ruxolitinib may help with some of the symptoms, including abdominal discomfort, pain under left ribs, early feelings of fullness from meals, night sweats, itching, and bone/muscle pain.Ruxolitinib is also used to treat a certain problem that may occur after certain stem cell or bone marrow transplants (graft versus host disease). It works by weakening your body's defense system (immune system).
HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking ruxolitinib and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with or without food as directed by your doctor, usually twice daily. If you are unable to swallow the tablets, ask your doctor about other ways to take this medication.The dosage is based on your medical condition, laboratory test results, response to treatment, and other medications you may be taking. Be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.To reduce your risk of side effects, your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully. Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.Do not stop taking ruxolitinib without consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Also, you may experience symptoms such as fever, trouble breathing, dizziness, and unusual bleeding/bruising. To prevent these symptoms while you are stopping treatment with this drug, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details. Report any new or worsening symptoms right away.Tell your doctor if your symptoms do not improve or if they worsen.
SIDE EFFECTS: Dizziness, diarrhea, headache, weight gain, or gas may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.People using this medication may have serious side effects. However, you have been prescribed this drug because your doctor has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.Tell your doctor right away if you have any serious side effects, including: unusual tiredness, easy bleeding/bruising, unusual skin changes.This medication may lower your ability to fight infections. This may make you more likely to get a serious (rarely fatal) infection or make any infection you have worse. Tell your doctor right away if you have any signs of infection (such as sore throat that doesn't go away, fever, chills, cough, painful skin rash/blisters).This medication may also increase your risk of getting a rare but very serious (sometimes fatal) brain infection (progressive multifocal leukoencephalopathy-PML). Get medical help right away if any of these rare but very serious side effects occur: clumsiness, loss of coordination, weakness, sudden change in your thinking (such as confusion, difficulty concentrating), difficulty moving your muscles, problems with speech, seizure, vision changes.Another medication similar to ruxolitinib has caused serious (possibly fatal) side effects, including heart problems, blood clots, and cancer (such as lymphoma). Before using ruxolitinib, tell your doctor or pharmacist if you have a history of heart disease, stroke, cancer, or any risk factors for heart disease (such as high blood pressure, diabetes, previous blood clots, high cholesterol, smoking or history of smoking). Discuss the risks and benefits of treatment with your doctor. Get medical help right away if you have symptoms such as shortness of breath/rapid breathing, chest/jaw/left arm pain, unusual sweating, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, sudden/severe headaches, trouble speaking, or weakness on one side of the body.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: See also Side Effects section.Before taking ruxolitinib, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: current/past/returning infections (such as herpes, tuberculosis), kidney disease, liver disease, cancer (such as skin cancer).This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Ruxolitinib can make you more likely to get infections or may make current infections worse. Stay away from anyone who has an infection that may easily spread (such as chickenpox, COVID-19, measles, flu, tuberculosis). Talk to your doctor if you have been exposed to an infection or for more details.Tell your health care professional that you are using ruxolitinib before having any immunizations/vaccinations. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this drug and for 2 weeks after stopping treatment. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: other drugs that weaken the immune system/increase the risk of infection (such as natalizumab, rituximab).
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as complete blood counts, cholesterol/triglyceride levels, skin exams) should be done before you start taking this medication and while you are taking it. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised March 2023. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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