You are using an outdated browser. We suggest you update your browser for a better experience. Click here for update.
Close this notification.
Skip to main content Skip to search

COVID-19: Get the latest updates or take a self-assessment.

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Find out more about hepatitis B virus screening and management.

Drug Formulary information is intended for use by healthcare professionals. It is not intended to be medical advice. Some of the information, including information about funding for cancer drugs, does not apply to all patients. Cancer treatment plans are unique to each patient. If you are a patient, please speak with your healthcare team to understand how this information applies to you.

RUXO

Cancer Type:
Hematologic, 
Myeloproliferative Neoplasms (MPNs)
Intent: Palliative
Regimen Category: Evidence-Informed
Funding:
Exceptional Access Program
    ruxolitinib - For patients with intermediate to high risk symptomatic myelofibrosis, or patients with symptomatic splenomegaly, according to specific criteria
Exceptional Access Program
    ruxolitinib - For the treatment of patients with polycythemia vera according to criteria.
A - Regimen Name

RUXO Regimen
Ruxolitinib


Disease Site
Hematologic
Myeloproliferative Neoplasms (MPNs)


Intent
Palliative

Regimen Category
Evidence-Informed :

Regimen is considered appropriate as part of the standard care of patients; meaningfully improves outcomes (survival, quality of life), tolerability or costs compared to alternatives (recommended by the Disease Site Team and national consensus body e.g. pan-Canadian Oncology Drug Review, pCODR).  Recommendation is based on an appropriately conducted phase III clinical trial relevant to the Canadian context OR (where phase III trials are not feasible) an appropriately sized phase II trial. Regimens where one or more drugs are not approved by Health Canada for any indication will be identified under Rationale and Use.


Rationale and Uses
  • For the treatment of splenomegaly and/or its associated symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis.
  • For the control of hematocrit in adult patients with polycythemia vera (PV) resistant to or intolerant of a cytoreductive agent.

 

 


Supplementary Public Funding

ruxolitinib
Exceptional Access Program (ruxolitinib - For patients with intermediate to high risk symptomatic myelofibrosis, or patients with symptomatic splenomegaly, according to specific criteria) (EAP Website)

ruxolitinib
Exceptional Access Program (ruxolitinib - For the treatment of patients with polycythemia vera according to criteria.) (EAP Website)

 
B - Drug Regimen

ruxolitinib

Starting dose is based on indication, platelet and neutrophil counts, and degree of hepatic or renal impairment. 

Treatment should not be started until neutrophils are ≥ 1 x 109/L and platelets ≥ 50 x 109/L.

ANC ( x109/L)
Platelet Count ( x109/L)
Starting Dose Myelofibrosis
Starting Dose Polycythemia Vera
> 1
> 200
20 mg PO twice daily
10 mg PO twice daily
> 1 100 - 200
15 mg PO twice daily
10 mg PO twice daily
> 1 75 - 99 10 mg PO twice daily 5 mg PO twice daily
> 1
50 - 74
5 mg PO twice daily
5 mg PO twice daily
≤ 1 < 50 Do not use Do not use

Refer to section E for dose titrations, if applicable.

back to top
 
C - Cycle Frequency

CONTINUOUS TREATMENT

Until disease progression or unacceptable toxicity; must be discontinued after 6 months if no evidence of improvement in symptoms or spleen size (MF) or after 16 months if no clinical benefit (PV).

 
D - Premedication and Supportive Measures

Antiemetic Regimen:

Minimal – No routine prophylaxis; PRN recommended

Other Supportive Care:

  • Perform tuberculosis skin test and/or Interferon-gamma release assay before treatment initiation. Caution with interpreting results in severely immunocompromised patients due to possible false negatives.

  • Patients should minimize exposure to risk factors for skin cancer such as exposure to sunlight.

 
E - Dose Modifications

Doses should be modified according to the protocol by which the patient is being treated.
 

Titration of Dose

If response to treatment is inadequate, escalation may proceed as detailed below. The maximum dose is 25 mg PO BID. 

The starting dose should not be increased within the first 4 weeks of treatment (for patients with MF) and 8 weeks of treatment (for PVD). 

Discontinue after 6 months if no evidence of improvement in symptoms or spleen size (MF) or after 16 months if no clinical benefit (PV).

 

ANC
 
Platelets (x 109/L) 
At 4 weeks (MF),
or 8 weeks (PV)
Every 2 weeks (or more) thereafter
>0.75
AND
>125 (and nadir >100)
↑ by 5mg bid
↑ by 5mg bid, if blood counts criteria are met.
≤0.75
OR
 ≤ 125 (or nadir < 100 )
Do not escalate.
Do not escalate.

 

Dosage with toxicity

Toxicity (x 109/L)
Action
Hb < 80 g/L  (PV pts only) Hold; when recovered, may restart at 5 mg PO twice daily and titrate gradually.
Hb < 120 g/L (PV pts only) Consider dose reduction, especially if  Hb < 100 g/L.
Platelets < 50 or ANC < 0.5
Hold; when platelet and ANC counts above these levels, may restart at 5 mg PO twice daily and titrate gradually.
Platelets 50 to < 125 (MF pts only) Refer to Dose Modification for Thrombocytopenia table below to minimize holds. May titrate gradually if appropriate.
PML, active tuberculosis, severe infection Hold and investigate; discontinue if confirmed.
Bleeding requiring intervention (regardless of platelet count) Hold until event is resolved; consider restart at previous dose if cause of bleeding controlled.  If the underlying cause persists, consider restart at a lower dose.

 

Dose Modification for Thrombocytopenia (MF)

 

Dose at Time of Platelet Decline

Platelet count

25 mg BID
20 mg BID
15 mg BID
10 mg BID
5 mg BID
 
New dose
New dose
New dose
New dose
New dose
100 to < 125

20 mg BID

15 mg BID

No change

No change

No change

75 to < 100

10 mg BID

10 mg BID

10 mg BID

No change

No change

50 to < 75 

5 mg BID

5 mg BID

5 mg BID

5 mg BID

No change



Hepatic Impairment

Avoid use in patients with hepatic impairment and platelets < 100 x 109/L.

Hepatic impairment
Ruxolitinib Dose (MF or PV)
None
No adjustment required.
Any degree

Start at 50% of usual dose*. Monitor carefully and adjust as appropriate.

*round up to the nearest dosage strength, if necessary.  


Renal Impairment

Avoid use in patients with moderate to severe renal impairment if platelets < 100 x 109/L.

Hemodialysis is not expected to enhance the elimination of ruxolitinib.

Renal Impairment
Ruxolitinib Dose (MF or PV)
Mild

No adjustment required.

Moderate (CrCl 30-50 mL/min)

Start at 50% of usual dose*. Monitor closely for toxicity.

Avoid if platelets < 100 x 109/L.

Severe (CrCl < 30 mL/min)

Patients on hemodialysis

Single dose given only after each dialysis session based on platelet count.

MF: 15 mg for platelets 100-200 x 109/L; 20mg for platelets > 200 x 109/L

PV: 10 mg

*round up to the nearest dosage strength, if necessary
 

Dosage in the elderly:

No dosage adjustments required. No overall differences in safety or effectiveness were observed between patients > 65 years of age and younger patients with MF or PV.
 

Dosage based on gender:

Female MF patients may be at a higher risk of anemia than male patients. Ruxolitinib clearance in women with MF was lower compared to men, however, no specific dose adjustment has been recommended.


 
F - Adverse Effects

Refer to drug monograph(s) for additional details of adverse effects.


Very common (≥ 50%)

Common (25-49%)

Less common (10-24%)

Uncommon (< 10%),

but may be severe or life-threatening

  • Myelosuppression ± infection, bleeding (may be severe, includes atypical infections (fungal, viral, TB), viral reactivation and endocarditis)
  • ↑ LFTs
  • Hyperlipidemia
  • Dizziness
  • Headache
  • Diarrhea
  • Musculoskeletal pain
  • Weight gain
  • Cough, dyspnea
  • Angina
  • Bradycardia
  • Prolonged PR interval
  • Venous thromboembolism
  • PML
  • Secondary malignancy
  • Withdrawal syndrome

 

 
G - Interactions

Refer to ruxolitinib drug monograph(s) for additional details.


  • Decrease ruxolitinib dose by 50% with concomitant use of strong CYP3A4 inhibitors
    • Monitor more frequently for cytopenias (e.g., twice a week) when starting a strong CYP3A4 inhibitor
    • Avoid concomitant use with ruxolitinib if platelets < 100
  • Monitor for cytopenias with concomitant use of moderate CYP3A4 inhibitors.
  • Decrease ruxolitinib dose by 50% if used with combined moderate CYP2C9 and CYP3A4 inhibitors (e.g. fluconazole); avoid fluconazole at doses > 200mg daily
    • Monitor more  frequently for cytopenias (e.g., twice a week) when starting combined moderate CYP2C9 and CYP3A4 inhibitors
    • Avoid concomitant use with ruxolitinib if platelets < 100
  • If possible, avoid drugs that decrease heart rate and/or prolong the PR interval due to increased risk of bradycardia.
 
H - Drug Administration and Special Precautions

Refer to ruxolitinib drug monograph(s) for additional details.


Administration

  • Administer with or without food with a glass of water.
  • The tablets should be swallowed whole; do not cut, break, dissolve, crush or chew the tablets.
  • Avoid grapefruit, starfruit, Seville oranges, their juices or products during treatment.
  • If a dose is missed, skip this dose and take the next dose as scheduled. Do not double the dose to make up for the missed one. 
  • Store at room temperature (15-25°C).
     

Contraindications

  • Patients who have a hypersensitivity to this drug or any of its components
  • Patients who have/had progressive multifocal leukoencephalopathy (PML)
     

Warnings/Precautions

  • Major adverse cardiovascular events (MACE), arterial/venous thrombosis, and/or malignancy, including fatal outcomes, have been reported with the JAK inhibitor tofacitinib. Consider the benefits and risks prior to initiating, or continuing, therapy of JAK inhibitors, especially in patients > 65 years, who are current or past smokers, or with other cardiovascular, thrombosis or malignancy risk factors.
  • Ruxolitinib can cause bradycardia and prolongation of PR interval; use with caution in patients on drugs with similar effects or with history of cardiovascular disease including bradycardia, syncope or arrhythmia, sick sinus syndrome, sinoatrial block, atrioventricular (AV) block, ischemic heart disease, or congestive heart failure.
  • Serious bacterial, mycobacterial, fungal, and viral infections including viral reactivation and opportunistic infections (in some cases fatal) have been reported. Do not administer ruxolitinib in patients with active tuberculosis or active serious infections.
  • Contains lactose and should not be used in patients with hereditary lactase/glucose or galactose disorders
     

Pregnancy/Lactation

  • Ruxolitinib is not recommended for use in pregnancy. Adequate contraception should be used by both sexes during treatment, and for at least 6 months after the last dose (general recommendation).
  • Breastfeeding is not recommended during treatment and for 2 weeks after the last dose.
  • Fertility effects: Probable
 
I - Recommended Clinical Monitoring

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Recommended Clinical Monitoring

  • CBC; baseline, every 2 - 4 weeks until doses are stabilized, and then as clinically indicated. Monitor more frequently for cytopenias (e.g., twice a week) when starting a strong CYP3A4 inhibitor or combined moderate CYP2C9 and CYP3A4 inhibitors.

  • Liver and renal function tests; baseline and as clinically indicated

  • Lipid monitoring; prior to starting, 4 weeks after starting, then as clinically indicated

  • Pulse rate and blood pressure; baseline and as clinically indicated

  • ECG; baseline and as clinically indicated

  • Clinical toxicity assessment for cardiovascular effects, infections (including ocular), bleeding, thrombosis, skin effects (including malignancies) and withdrawal syndrome (if applicable); at each visit

  • Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version


back to top
 
J - Administrative Information

Outpatient prescription for home administration


 
K - References

Ruxolitinib drug monograph, Ontario Health (Cancer Care Ontario).

Harrison C, Kiladjian J, Kathrin Al-Ali H, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366-787-98.

Tefferi A and Pardanani A.  Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clinic Proceedings 2011;86(12):1188-91.

Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366:799-807.

February 2023 Updated Drug Regimen, Dose Modifications, Adverse Effects, Interactions, Drug Administration and Special Precautions, and Monitoring sections


back to top
 
M - Disclaimer

Regimen Abstracts
A Regimen Abstract is an abbreviated version of a Regimen Monograph and contains only top level information on usage, dosing, schedule, cycle length and special notes (if available). It is intended for healthcare providers and is to be used for informational purposes only. It is not intended to constitute or be a substitute for medical advice, and all uses of the Regimen Abstract are subject to clinical judgment. Such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability, and Cancer Care Ontario disclaims all liability for the use of this information, and for any claims, actions, demands or suits that arise from such use.
Information in regimen abstracts is accurate to the extent of the ST-QBP regimen master listings, and has not undergone the full review process of a regimen monograph.  Full regimen monographs will be published for each ST-QBP regimen as they are developed.
Regimen Monographs
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.
The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.
Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.
While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.
CCO and the Formulary’s content providers shall have no liability, whether direct, indirect, consequential, contingent, special, or incidental, related to or arising from the information in the Formulary or its use thereof, whether based on breach of contract or tort (including negligence), and even if advised of the possibility thereof. Anyone using the information in the Formulary does so at his or her own risk, and by using such information, agrees to indemnify CCO and its content providers from any and all liability, loss, damages, costs and expenses (including legal fees and expenses) arising from such person’s use of the information in the Formulary.