Ruxolitinib
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From MedlinePlus, U.S. National Library of Medicine
Janus Kinase Inhibitor, Kinase Inhibitor
Dosing in kidney impairment
Dose Modifications for Renal or Hepatic Impairment Moderate to Severe Renal Impairment or End Stage Renal Disease on Dialysis Modify the JAKAFI/JAKAFI XR dosage for patients with moderate (CLcr 30 to 59 mL/min) to severe (CLcr 15 to 29 mL/min) renal impairment or end stage renal disease (ESRD) on dialysis according to Table 13.
Avoid use of JAKAFI/JAKAFI XR in patients with ESRD (CLcr less than 15 mL/min) not requiring dialysis [see Use in Specific Populations] . [See table below.] Less than 50 x 10 9 /L Avoid use [see Use in Specific Populations] ESRD on dialysis 100 to 200 x 10 9 /L JAKAFI 15 mg once after dialysis session Do not use JAKAFI XR Greater than 200 x 10 9 /L JAKAFI 20 mg once after dialysis session Do not use JAKAFI XR Patients with PV Moderate or Severe Any JAKAFI 5 mg twice daily JAKAFI XR 11 mg once daily ESRD on dialysis Any JAKAFI 10 mg once after dialysis session Do not use JAKAFI XR Patients with aGVHD Moderate or Severe Any JAKAFI 5 mg once daily Do not use JAKAFI XR ESRD on dialysis Any JAKAFI 5 mg once after dialysis session Do not use JAKAFI XR P atients with cGVHD Moderate or Severe Any JAKAFI 5 mg twice daily JAKAFI XR 11 mg once daily ESRD on dialysis Any JAKAFI 10 mg once after dialysis session Do not use JAKAFI XR Hepatic Impairment Modify the JAKAFI/JAKAFI XR dosage for patients with hepatic impairment according to Table 14. [See table below.]
| CLcr = creatinine clearance; ESRD = end stage renal disease | |||
| Renal Impairment Status | Platelet Count | JAKAFI Recommended Starting Dosage | JAKAFI XR Recommended Starting Dosage |
| Patients with MF | |||
| Moderate or Severe | Greater than 150 x 109/L | No dose adjustment | |
| 100 to 150 x 109/L | JAKAFI 10 mg twice daily | JAKAFI XR 22 mg once daily | |
| 50 to less than 100 x 109/L | JAKAFI 5 mg once daily | Do not use JAKAFI XR | |
| Less than 50 x 109/L | Avoid use [see Use in Specific Populations (8.6)] | ||
| ESRD on dialysis | 100 to 200 x 109/L | JAKAFI 15 mg once after dialysis session | Do not use JAKAFI XR |
| Greater than 200 x 109/L | JAKAFI 20 mg once after dialysis session | Do not use JAKAFI XR | |
| Patients with PV | |||
| Moderate or Severe | Any | JAKAFI 5 mg twice daily | JAKAFI XR 11 mg once daily |
| ESRD on dialysis | Any | JAKAFI 10 mg once after dialysis session | Do not use JAKAFI XR |
| Patients with aGVHD | |||
| Moderate or Severe | Any | JAKAFI 5 mg once daily | Do not use JAKAFI XR |
| ESRD on dialysis | Any | JAKAFI 5 mg once after dialysis session | Do not use JAKAFI XR |
| Patients with cGVHD | |||
| Moderate or Severe | Any | JAKAFI 5 mg twice daily | JAKAFI XR 11 mg once daily |
| ESRD on dialysis | Any | JAKAFI 10 mg once after dialysis session | Do not use JAKAFI XR |
Dosing in liver impairment
Hepatic Impairment Exposure of ruxolitinib increased with mild (Child-Pugh A), moderate (Child-Pugh B), and severe (Child-Pugh C) hepatic impairment [see Clinical Pharmacology]. Reduce JAKAFI/JAKAFI XR dosage as recommended in patients with MF or PV with hepatic impairment [ see Dosage and Administration ] . Reduce JAKAFI dosage as recommended for patients with Stage 4 liver aGVHD.
Monitor blood counts more frequently for toxicity and modify the JAKAFI/JAKAFI XR dosage for adverse reactions if they occur for patients with Score 3 liver cGVHD [ see Dosage and Administration and Clinical Pharmacology].
| Hepatic Impairment Status | Platelet Count | JAKAFI Recommended Starting Dosage | JAKAFI XR Recommended Starting Dosage |
| Patients with MF | |||
| Mild, Moderate, or Severe (Child-Pugh Class A, B, C) | Greater than 150 x 109/L | No dose adjustment | |
| 100 x 109/L to 150 x 109/L | 10 mg twice daily | 22 mg once daily | |
| 50 to less than 100 x 109/L | JAKAFI 5 mg once daily | Do not use JAKAFI XR | |
| Less than 50 x 109/L | Avoid use [see Use in Specific Populations (8.7)] | ||
| Patients with PV | |||
| Mild, Moderate, or Severe (Child-Pugh Class A, B, C) | Any | 5 mg twice daily | 11 mg once daily |
| Patients with aGVHD | |||
| Mild, Moderate, or Severe based on NCI criteria without liver GVHD | Any | No dose adjustment | |
| Stage 1, 2 or 3 Liver aGVHD | Any | No dose adjustment | |
| Stage 4 Liver aGVHD | Any | JAKAFI 5 mg once daily | Do not use JAKAFI XR |
| Patients with cGVHD | |||
| Mild, Moderate, or Severe based on NCI criteria without liver GVHD | Any | No dose adjustment | |
| Score 1 or 2 Liver cGVHD | Any | No dose adjustment | |
| Score 3 Liver cGVHD | Any | Monitor blood counts more frequently for toxicity and modify the JAKAFI/JAKAFI XR dosage for adverse reactions if they occur [see Dosage and Administration (2.4, 2.5)]. | |
Preparation and administration
Method of Administration JAKAFI JAKAFI is dosed orally and can be administered with or without food. If a dose is missed, the patient should not take an additional dose, but should take the next usual prescribed dose. When discontinuing JAKAFI therapy for reasons other than potentially life-threatening toxicities, gradually taper the dose of JAKAFI, for example by 5 mg twice daily each week.
For patients unable to ingest tablets, JAKAFI can be administered through a nasogastric tube (8 French or greater) as follows: Suspend 1 tablet in approximately 40 mL of water with stirring for approximately 10 minutes. Within 6 hours after the tablet has dispersed, the suspension can be administered through a nasogastric tube using an appropriate syringe.
The tube should be rinsed with approximately 75 mL of water. The effect of tube feeding preparations on JAKAFI exposure during administration through a nasogastric tube has not been evaluated. JAKAFI XR JAKAFI XR is dosed orally and can be administered with or without food. Swallow JAKAFI XR tablets whole. Do not split, chew, or crush.
If a dose is missed, the patient should not take an additional dose, but should take the next usual prescribed dose. When discontinuing JAKAFI XR therapy for reasons other than potentially life-threatening toxicities, gradually taper the dose of JAKAFI XR, for example by 11 mg once daily each week for JAKAFI XR.
Drug interactions
Check ruxolitinib against a medication listLabel text (4 paragraphs)
Fluconazole: Avoid concomitant use with fluconazole doses greater than 200 mg. Reduce JAKAFI/JAKAFI XR dosage with fluconazole doses less than or equal to 200 mg. ( 2.6 , 7 ) Strong CYP3A4 Inhibitors: Reduce, interrupt, or discontinue JAKAFI/JAKAFI XR doses as recommended except in patients with acute or chronic graft-versus-host-disease. ( 2.6 , 7 )
7.1 Effect of Other Drugs on JAKAFI/JAKAFI XR Fluconazole Concomitant use of JAKAFI/JAKAFI XR with fluconazole increases ruxolitinib exposure [ see Clinical Pharmacology ( 12.3 )] , which may increase the risk of exposure-related adverse reactions. Avoid concomitant use of JAKAFI/JAKAFI XR with fluconazole doses of greater than 200 mg daily. Reduce the JAKAFI/JAKAFI XR dosage when used concomitantly with fluconazole doses of less than or equal to 200 mg [ see Dosage and Administration ( 2.6 )] .
Strong CYP3A4 Inhibitors Concomitant use of JAKAFI/JAKAFI XR with strong CYP3A4 inhibitors increases ruxolitinib exposure [ see Clinical Pharmacology ( 12.3 )] , which may increase the risk of exposure-related adverse reactions. Reduce the JAKAFI/JAKAFI XR dosage when used concomitantly with strong CYP3A4 inhibitors except in patients with aGVHD or cGVHD [ see Dosage and Administration ( 2.6 )] . Strong CYP3A4 Inducers Concomitant use of JAKAFI/JAKAFI XR with strong CYP3A4 inducers may decrease ruxolitinib exposure [ see Clinical Pharmacology ( 12.3 )] , which may reduce efficacy of JAKAFI/JAKAFI XR.
Monitor patients frequently and adjust the JAKAFI/JAKAFI XR dose based on safety and efficacy [ see Clinical Pharmacology ( 12.3 )] .
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
CLikelihood score C: Probable cause of reactivation of hepatitis B in susceptible patients.
Ruxolitinib is a small molecule Janus kinase inhibitor that is used in the treatment of intermediate or high risk myelofibrosis and resistant forms of polycythemia vera and graft-vs-host disease. Ruxolitinib is associated with transient and usually mild elevations in serum aminotransferase during therapy and to rare instances of self-limited, clinically apparent idiosyncratic acute liver injury as well as to cases of reactivation of hepatitis B in susceptible individuals.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary When pregnant rats and rabbits were administered ruxolitinib during the period of organogenesis adverse developmental outcomes occurred at doses associated with maternal toxicity (see Data) . There are no studies with the use of JAKAFI/JAKAFI XR in pregnant women to inform drug-associated risks. The background risk of major birth defects and miscarriage for the indicated populations is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The background risk in the U.S. general population of major birth defects is 2% to 4% and miscarriage is 15% to 20% of clinically recognized pregnancies.
Data Animal Data Ruxolitinib was administered orally to pregnant rats or rabbits during the period of organogenesis, at doses of 15, 30, or 60 mg/kg/day in rats and 10, 30, or 60 mg/kg/day in rabbits. There were no treatment-related malformations. Adverse developmental outcomes, such as decreases of approximately 9% in fetal weights were noted in rats at the highest and maternally toxic dose of 60 mg/kg/day. This dose results in an exposure (AUC) that is approximately 2 times the clinical exposure at the maximum recommended dose of 25 mg twice daily.
In rabbits, lower fetal weights of approximately 8% and increased late resorptions were noted at the highest and maternally toxic dose of 60 mg/kg/day. This dose is approximately 7% of the clinical exposure at the maximum recommended dose. In a pre- and post-natal development study in rats, pregnant animals were dosed with ruxolitinib from implantation through lactation at doses up to 30 mg/kg/day. There were no drug-related adverse findings in pups for fertility indices or for maternal or embryofetal survival, growth, and development parameters at the highest dose evaluated (34% the clinical exposure at the maximum recommended dose of 25 mg twice daily).
Breastfeeding (LactMed)
No information is available on the clinical use of ruxolitinib during breastfeeding. Because ruxolitinib is 97% bound to plasma proteins, the amount in milk is likely to be low. The manufacturer recommends that breastfeeding be discontinued during ruxolitinib therapy and for 2 weeks after the last dose for the oral tablets and for 4 weeks after the last dose for the topical cream. However, ruxolitinib cream is approved for direct application in children as young as 2 years of age.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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