Ruxolitinib is a medication that belongs to a class of drugs called Janus kinase (JAK) inhibitors. It is primarily used to treat certain blood disorders, specifically myelofibrosis and polycythemia vera.

Myelofibrosis is a rare bone marrow disorder characterized by the abnormal production of blood cells, leading to the formation of scar tissue in the bone marrow. Ruxolitinib helps to reduce symptoms such as enlarged spleen, fatigue, and night sweats, and it can improve overall quality of life for people with myelofibrosis.

Polycythemia vera is a condition characterized by the overproduction of red blood cells in the bone marrow. Ruxolitinib is used to reduce the production of these cells and manage related symptoms such as itching, headache, and dizziness.

Ruxolitinib works by inhibiting the activity of certain enzymes called JAK1 and JAK2, which play a role in regulating the production of blood cells. By blocking these enzymes, ruxolitinib helps to normalize blood cell production and reduce the symptoms associated with myelofibrosis and polycythemia vera.

Ruxolitinib (Jakafi, Jakavi) Uses:

• Acute Graft-versus-host disease:
  • Treatment of steroid-refractory acute graft-versus-host disease (GVHD) in both adult and pediatric patients ≥12 years
• Myelofibrosis:
  • Treatment of intermediate or high-risk myelofibrosis in adults, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis
• Polycythemia vera:
  • Treatment of polycythemia vera in adults with an inadequate response to or intolerance to hydroxyurea
• Off Label Use of Ruxolitinib in Adults:
  • Treatment of chronic graft vs host disease

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Ruxolitinib (Jakafi, Jakavi) Dose in Adults

Ruxolitinib Dosage recommendations by the Manufacturer:

Initial Starting Dose (Manufacturer Recommendations)
Platelet Count	Starting Dose
Greater than 200 X 109/L	20 mg orally twice daily
100 x 109/L to 200 x 109/L	15 mg orally twice daily

Ruxolitinib (Jakafi, Jakavi) dose in the treatment of steroid-refractory acute Graft-versus-host disease:

The recommended oral dosing regimen for ruxolitinib in this indication is as follows:

• Initial dose: 5 mg twice daily.
• Consideration for dose increase: After at least 3 days of treatment, if the absolute neutrophil count (ANC) and platelet levels have not decreased by at least 50% compared to baseline (first day of ruxolitinib), the dose can be increased to 10 mg twice daily.
• Consideration for tapering: If a response occurs and therapeutic corticosteroid doses have been discontinued, ruxolitinib may be tapered after 6 months of therapy. The tapering process involves reducing the dose by one level approximately every 8 weeks. The suggested tapering schedule is as follows: 10 mg twice daily to 5 mg twice daily, and then to 5 mg once daily.
• Retreatment consideration: If signs or symptoms of acute GVHD recur during or after the tapering of ruxolitinib, retreatment with ruxolitinib may be considered.

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Ruxolitinib (Jakafi, Jakavi) Dose in the treatment of chronic steroid-refractory Graft-versus-host disease  (off-label):

• The recommended oral dose of ruxolitinib in the off-label treatment of chronic steroid-refractory Graft-versus-host disease is between 5 to 10 mg taken twice daily, based on a study conducted by Zeiser in 2015.

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Ruxolitinib (Jakafi, Jakavi) Dose in the Treatment of Myelofibrosis:

In the treatment of myelofibrosis, the recommended dose of ruxolitinib is based on the patient's platelet count.

The initial doses are as follows:

• Platelets >200,000/mm³: 20 mg twice daily orally.
• Platelets 100,000 to 200,000/mm³: 15 mg twice daily orally.
• Platelets 50,000 to <100,000/mm³: 5 mg twice daily orally.

For patients with a baseline platelet count of 100,000/mm³ or higher before starting treatment with ruxolitinib::

• The dose can be adjusted based on the patient's response to treatment.
• For patients with a baseline platelet count of 100,000/mm³ or higher, if there is an insufficient response with adequate platelet and neutrophil counts, the dose may be increased by 5 mg twice daily increments.
• The maximum dose should not exceed 25 mg twice daily.
• The dose should not be increased during the initial 4 weeks and no more frequently than every 2 weeks.
• If there is no reduction in spleen size or improvement in symptoms after 6 months of treatment, the medication may be discontinued.
• When discontinuing for reasons other than thrombocytopenia, a gradual tapering of the dose by approximately 5 mg twice daily per week is recommended.

Dosage modification for bleeding:

• In cases where bleeding requiring intervention occurs, regardless of the platelet count, treatment should be interrupted until the bleeding is resolved.
• Resuming treatment at the prior dose can be considered if the underlying cause of bleeding has been resolved, or at a reduced dose if the underlying cause persists.

For patients with a baseline platelet count between 50,000 and less than 100,000/mm³ before starting treatment with ruxolitinib, the following dosage modification guidelines apply:

• If there is an insufficient response (no improvement) with adequate platelet and neutrophil counts, the dose may be increased gradually in 5 mg increments daily.
• The maximum dose should not exceed 10 mg twice daily.
• Similar to the previous scenario, the dose should not be increased during the first 4 weeks and not more frequently than every 2 weeks.
• If there is no reduction in spleen size or improvement in symptoms after 6 months of treatment, discontinuation of ruxolitinib may be considered.

Dose increases may be considered for patients with a baseline platelet count between 50,000 and less than 100,000/mm³ if they meet all of the following situations:

• Platelet count remains at least 40,000/mm³ and did not decrease by more than 20% in the previous 4 weeks.
• Absolute neutrophil count (ANC) is above 1,000/mm³.
• No adverse events or hematological toxicity that led to dose reduction or interruption occurred in the previous 4 weeks.

Therapy discontinuation:

• Gradual tapering off: If discontinuing ruxolitinib for reasons other than thrombocytopenia (low platelet count), it is generally recommended to gradually reduce the dose. This is usually done by decreasing the dose by approximately 5 mg twice daily each week.

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Ruxolitinib (Jakafi, Jakavi) Dose in the treatment of Polycythemia vera:

• In the treatment of polycythemia vera, the recommended initial dose of ruxolitinib is 10 mg taken twice daily orally.
• The dose can be adjusted based on the patient's response to treatment and considering safety considerations.

Dose modification due to insufficient response:

• If the response to ruxolitinib is insufficient, and the platelet, hemoglobin, and neutrophil counts are within an adequate range, the dose may be increased in increments of 5 mg twice daily.
• The maximum dose should not exceed 25 mg twice daily.
• It's important not to increase the dose during the first 4 weeks of treatment and no more frequently than every 2 weeks.
• Consideration for dose increases is given to patients who meet the following conditions:
  • Inadequate efficacy demonstrated by continued need for phlebotomy, white blood cell count (WBC) above the upper limit of the normal range, platelet count above the upper limit of the normal range, or less than a 25% reduction in palpable spleen size from baseline.
  • Platelet count is equal to or greater than 140,000/mm³.
  • Hemoglobin level is equal to or greater than 12 g/dL.
  • Absolute neutrophil count (ANC) is equal to or greater than 1,500/mm³.
• Therapy discontinuation:
  • When discontinuing ruxolitinib for reasons other than thrombocytopenia (low platelet count), it is advisable to gradually taper off the medication. This typically involves reducing the dose by approximately 5 mg twice daily each week.

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Ruxolitinib (Jakafi, Jakavi) Dosage adjustment with concomitant therapy

When using ruxolitinib in combination with certain medications, such as CYP3A4 inhibitors, dosage adjustments may be necessary.

Here are the recommended dosage adjustments for different scenarios:

• Graft-versus-host disease (acute; treatment), steroid-refractory:
  • Ketoconazole (a CYP3A4 inhibitor): Administer ruxolitinib at a dose of 5 mg once daily.
  • Other CYP3A4 inhibitors: No dosage adjustment for ruxolitinib is necessary. However, if using itraconazole (another CYP3A4 inhibitor) concurrently, it is advised to monitor blood counts more frequently and adjust the ruxolitinib dose if needed.

• Myelofibrosis and Polycythemia vera:
  • Strong CYP3A4 inhibitors and fluconazole (≤200 mg):
    • Myelofibrosis initial dose:
      • Platelets ≥100,000/mm³: 10 mg twice daily.
      • Platelets 50,000/mm³ to <100,000/mm³: 5 mg once daily. Monitor closely and adjust dose further based on safety and efficacy.
    • Polycythemia vera initial dose: 5 mg twice daily.
  • Myelofibrosis and Polycythemia vera on stable dose:
    • Stabilized on ruxolitinib ≥10 mg twice daily: Reduce dose by 50% (rounded up to the closest available tablet strength).
    • Stabilized on ruxolitinib 5 mg twice daily: Reduce dose to 5 mg once daily.
    • Stabilized on ruxolitinib 5 mg once daily: Avoid strong CYP3A4 inhibitors or fluconazole. If they must be used, interrupt ruxolitinib treatment for the duration of the strong CYP3A4 inhibitor or fluconazole use. Monitor closely and adjust the dose further based on safety and efficacy.

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Ruxolitinib (Jakafi) Dose Adjustment in Patients with Thrombocytopenia [Ref]:

Platelet counts	Dose at Time of Platelet Decline (twice daily dosing)
Platelet Counts	25	20	15	10	5
	A new Dose is administered Twice daily
100 to less than 125 X 109 /L	20	15	No Change	No Change	No Change
75 to less than 100 X 109 /L	10	10	10	No Change
50 to less than 75 X 109 /L	5	5	5	5
Less than 50 X 109 /L	Hold

Ruxolitinib (Jakafi, Jakavi) Dose in Children

Ruxolitinib (Jakafi, Jakavi) Dose in the treatment of Acute Steroid-refractory Graft-versus-host disease (GVHD):

Patient Group	Dosing Information
Children ≥12 years	Start orally with 5 mg twice daily. It is recommended to consider increasing the dosage of ruxolitinib to 10 mg twice daily after at least 3 days of treatment if the absolute neutrophil count (ANC) and platelet levels have not decreased by 50% or more compared to the baseline levels (measured on the first day of ruxolitinib administration).
Children and Adolescents (Weight-directed dosing)	Limited data available. Dosing based on a study of 13 patients aged 1.6 to 16.5 years receiving ruxolitinib for steroid-refractory GVHD.
For patients weighing less than 25 kg	The initial dose of ruxolitinib is 2.5 mg twice daily. If this dose is well tolerated by the patient, the dose can be doubled on a weekly basis. The maximum dose for patients in this weight category is 10 mg twice daily. This gradual increase in dosage allows for close monitoring of the patient's response and helps ensure their safety and well-being.
For patients weighing 25 kg or more	The initial dose of ruxolitinib is 5 mg twice daily. If the patient tolerates this dose well, the dosage can be doubled on a weekly basis. The maximum dose for patients in this weight category is 10 mg twice daily. This gradual dose escalation allows for careful observation of the patient's response and helps ensure their safety and effectiveness of treatment.
Tapering of therapy	After 6 months of ruxolitinib therapy, if a positive response is achieved and the patient is no longer taking therapeutic corticosteroids, it is advisable to consider gradually reducing the dose. The tapering process involves decreasing the dose level approximately every 8 weeks. For example, if the patient is currently taking 10 mg twice daily, the dose can be reduced to 5 mg twice daily, and then further reduced to 5 mg once daily. It's important to monitor the patient closely during the tapering period. If signs or symptoms of acute GVHD reappear during or after the tapering process, retreatment with ruxolitinib may be necessary. This approach helps manage the medication effectively and adjust the dosage according to the patient's needs.

Ruxolitinib (Jakafi, Jakavi) Dosage adjustment with concomitant strong CYP3A4 inhibitors:

Patient Group	Concomitant CYP3A4 Inhibitor	Dosing Information
Children ≥12 years	Ketoconazole	The recommended dose of ruxolitinib is 5 mg orally once daily.
Children ≥12 years	Other CYP3A4 inhibitors	No dosage adjustment is necessary for ruxolitinib when it is used concomitantly with other CYP3A4 inhibitors, except for itraconazole. If itraconazole is being used alongside ruxolitinib, it is important to closely monitor the patient's blood counts more frequently.

Ruxolitinib (Jakafi, Jakavi) Dosage adjustment for toxicity:

Patient Group	Ruxolitinib Regimen	Dosage Reduction
Children ≥12 years	10 mg twice daily	Reduce dose to 5 mg twice daily.
Children ≥12 years	5 mg twice daily	Reduce dose to 5 mg once daily.
Children ≥12 years	5 mg once daily	Interrupt ruxolitinib treatment until recovery occurs.

Ruxolitinib (Jakafi, Jakavi) Dosage modification for hematologic toxicity:

• Clinically significant thrombocytopenia:
  • If the patient experiences a clinically significant drop in platelet count, the dose of ruxolitinib should be reduced by 1 dose level.
  • Once the platelet count recovers to the previous values, the dose may be increased back to the prior dose level.
• ANC (Absolute Neutrophil Count) <1,000/mm³ related to ruxolitinib treatment:
  • If the patient's ANC drops below 1,000/mm³ due to ruxolitinib treatment, the treatment should be interrupted for up to 14 days.
  • Upon recovery of the ANC, the treatment can be restarted at a dose level lower than the previous dose.

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Ruxolitinib (Jakafi) Pregnancy Risk Category: C

• Clinical studies on the use of this drug during human pregnancies have not been conducted.
• However, animal studies conducted during the development of organs (organogenesis) did not show any harmful effects on the development of offspring (teratogenic effects).
• However, it was observed that the fetal weight was significantly lower compared to the control group.

Use during breastfeeding:

• The excretion of the drug into breast milk is currently unknown.
• However, studies conducted on rats showed that the drug and its metabolites were found to be 13 times more concentrated in the breast milk compared to the plasma of the rats.

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Ruxolitinib (Jakafi, Jakavi) Dose in Kidney Disease:

Acute treatment of steroid-refractory Graft-versus-host disease:

• For patients with a kidney function of 15 to 59 mL/minute and any platelet count, the initial dose is 5 mg once daily. Additional adjustments to the dose may be needed, and close monitoring is important.
• For patients with end-stage renal disease (ESRD) who are on dialysis and have any platelet count, the initial dose is 5 mg once after dialysis. Further dose adjustments should be made carefully, with close monitoring.
• Ruxolitinib is not recommended for use in patients with ESRD who do not require dialysis.

Myelofibrosis:

• For patients with a kidney function of Creatinine Clearance (CrCl) 15 to 59 mL/minute and platelets >150,000/mm³, no adjustment of the dose is required.
• For patients with a kidney function of Creatinine Clearance (CrCl) 15 to 59 mL/minute and platelets 100,000 to 150,000/mm³, the starting dose is 10 mg twice daily. Further dose adjustments should be made with careful monitoring.
• For patients with a kidney function of Creatinine Clearance (CrCl) 15 to 59 mL/minute and platelets 50,000 to <100,000/mm³, the starting dose is 5 mg once daily. Additional dose adjustments should be made with careful monitoring.
• Ruxolitinib should be avoided in patients with a kidney function of Creatinine Clearance (CrCl) 15 to 59 mL/minute and platelets <50,000/mm³.
• For patients with end-stage renal disease (ESRD) on dialysis and platelets 100,000 to 200,000/mm³, the starting dose is 15 mg once after dialysis. Subsequent doses should be administered after dialysis-on-dialysis days. Additional dose adjustments should be made with frequent monitoring.
• For patients with end-stage renal disease (ESRD) on dialysis and platelets >200,000/mm³, the starting dose is 20 mg once after dialysis. Subsequent doses should be administered after dialysis-on-dialysis days. Additional dose adjustments should be made with frequent monitoring.
• Ruxolitinib should be avoided in patients with ESRD not requiring dialysis.

Polycythemia vera:

• For patients with a kidney function of Creatinine Clearance (CrCl) 15 to 59 mL/minute and any platelet count, the starting dose is 5 mg twice daily. Additional dose adjustments should be made with frequent monitoring.
• For patients with end-stage renal disease (ESRD) on dialysis and any platelet count, the starting dose is 10 mg once after dialysis. Additional dose adjustments should be made with careful monitoring.
• Ruxolitinib should be avoided in patients with ESRD not requiring dialysis.
• Hemodialysis is not expected to affect the elimination of ruxolitinib.

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Ruxolitinib (Jakafi, Jakavi) Dose in Liver disease:

Graft-versus-host disease (acute; treatment), steroid-refractory

• Dosage adjustment for preexisting hepatic impairment:
  • For patients with mild to severe hepatic impairment (based on NCI criteria) and any platelet count, no dosage adjustment is necessary.
• Dosage adjustment for stage 3 or 4 liver graft-versus-host disease (GVHD) and any platelet count:
  • For patients with stage 3 or 4 liver GVHD, it is recommended to monitor blood counts more frequently and consider dosing ruxolitinib at 5 mg once daily.

Hepatoxicity during treatment (refer to Dosing – Adjustment for Toxicity for acute GVHD dosage reduction levels):

• Dosage adjustments based on total bilirubin elevation:
  • If the total bilirubin is 3 to 5 times the upper limit of normal (ULN), continue ruxolitinib at a dose level lower until recovery.
  • If the total bilirubin is >5 to 10 times the ULN, interrupt ruxolitinib treatment for up to 14 days. Once the bilirubin recovers to ≤1.5 times the ULN, you may resume treatment at the current dose.
  • If the total bilirubin is >10 times the ULN, interrupt ruxolitinib treatment for up to 14 days. Once the bilirubin recovers to ≤1.5 times the ULN, you may resume treatment at a dose level lower.
  • If the total bilirubin elevation is associated with liver GVHD and the total bilirubin is >3 times the ULN, continue ruxolitinib at a dose level lower until recovery.

Myelofibrosis:

• If there is mild to severe hepatic impairment and the platelet count is >150,000/mm, no dosage adjustment is necessary.
• If there is mild to severe hepatic impairment and the platelet count is between 100,000 and 150,000/mm, the starting dose is 10 mg twice daily. Additional dose adjustments should be made with careful monitoring.
• If there is mild to severe hepatic impairment and the platelet count is between 50,000 and <100,000/mm, the starting dose is 5 mg once daily. Additional dose adjustments should be made with careful monitoring.
• If there is mild to severe hepatic impairment and the platelet count is <50,000/mm, ruxolitinib should be avoided.

Polycythemia vera:

• For individuals with mild to severe hepatic impairment (Child-Pugh class A, B, or C) and any platelet count, the starting dose of ruxolitinib is 5 mg twice daily. It is important to closely monitor the individual and make additional dose adjustments as needed, while maintaining careful monitoring throughout the treatment.

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Common Side Effects of Ruxolitinib (Jakafi, Jakavi):

• Central Nervous System:
  • Dizziness
  • Headache
  • Fatigue
  • Insomnia
• Dermatologic:
  • Bruise
  • Pruritus
• Endocrine & Metabolic:
  • Increased Serum Cholesterol
  • Hypertriglyceridemia
• Gastrointestinal:
  • Diarrhea
  • Abdominal Pain
• Hematologic & Oncologic:
  • Anemia
  • Thrombocytopenia
  • Neutropenia
• Hepatic:
  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase
• Neuromuscular & Skeletal:
  • Muscle Spasm
• Respiratory:
  • Dyspnea

Less Common Side Effects Of Ruxolitinib (Jakafi, Jakavi):

• Cardiovascular:
  • Edema
  • Hypertension
• Endocrine & Metabolic:
  • Weight Gain
• Gastrointestinal:
  • Constipation
  • Nausea
  • Flatulence
• Genitourinary:
  • Urinary Tract Infection
• Infection:
  • Herpes Zoster Infection
• Neuromuscular & Skeletal:
  • Arthralgia
  • Asthenia
• Respiratory:
  • Nasopharyngitis
  • Cough
  • Epistaxis

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Contraindications to Ruxolitinib (Jakafi, Jakavi):

According to the manufacturer's US labeling, there are no specific contraindications listed for ruxolitinib.

In the Canadian labeling, ruxolitinib is contraindicated in individuals with hypersensitivity to ruxolitinib or any component of the formulation or container, as well as those with a history of or current progressive multifocal leukoencephalopathy.

Warnings and precautions

Hematologic toxicities:

• Hematologic toxicity is a possible side effect of ruxolitinib, which includes low platelet count (thrombocytopenia), low red blood cell count (anemia), and low white blood cell count (neutropenia).
• It's important to monitor blood counts regularly, especially at the beginning of treatment and as needed.
• If thrombocytopenia occurs, the dosage may be adjusted or treatment may be temporarily stopped, and platelet transfusions can be given if necessary.
• Anemia may require blood transfusions, and dose modification can be considered.
• Neutropenia can be managed by temporarily stopping treatment.

Infections

• Infections can be a serious concern when taking ruxolitinib.
• It's important to make sure any active infections are treated and resolved before starting treatment.
• During treatment, it's crucial to watch out for signs and symptoms of infections, including tuberculosis and herpes zoster (shingles).
• Following clinical guidelines, prophylactic antibiotics may be used to prevent infections.
• If symptoms of active tuberculosis or herpes zoster develop, immediate treatment is recommended.
• Before starting treatment, assess patients for risk factors of tuberculosis and consider testing for latent infection in high-risk individuals.
• If tuberculosis is detected, the decision to continue treatment should be carefully evaluated.
• There have been rare cases of progressive multifocal leukoencephalopathy (PML) reported, so treatment should be discontinued and evaluated if PML is suspected.
• Additionally, there have been reports of increased hepatitis B viral load in patients with chronic hepatitis B infection, although the impact of ruxolitinib on this condition is uncertain.
• Monitoring and appropriate management are necessary in such cases.

Lipid abnormalities

• Ruxolitinib use has been linked to higher levels of certain lipids in the blood, such as total cholesterol, LDL cholesterol, and triglycerides.
• It is important to evaluate lipid levels about 8 to 12 weeks after starting ruxolitinib treatment.
• If hyperlipidemia (high lipid levels) is detected, it should be closely monitored and managed appropriately.
• This may involve lifestyle modifications, dietary changes, and, in some cases, medication to control lipid levels and reduce the risk of associated complications.
• Regular monitoring and management of lipid abnormalities are necessary to promote overall health.

Non-melanoma skin carcinoma:

• Patients who have received ruxolitinib should undergo periodic skin examinations due to reports of non-melanoma skin cancers, including basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma.
• These types of skin cancers can occur in individuals using ruxolitinib.
• Regular skin examinations help in early detection and prompt treatment if any suspicious skin lesions are identified.
• It is important to follow up with a healthcare professional for these examinations to ensure the ongoing health and well-being of the patient.

Hepatic impairment

• In patients with hepatic impairment, initial dosage reduction may be necessary.
• For individuals with myelofibrosis, it is important to avoid the use of ruxolitinib if their platelet count is less than 50,000/mm and they also have hepatic impairment, regardless of its severity.
• Patients with stage 3 or 4 liver graft-versus-host disease (GVHD) should have their blood counts monitored more frequently, and dosage reduction may be considered in such cases.
• It is essential to work closely with a healthcare professional to determine the appropriate dosage and monitor the patient's liver function and blood counts regularly to ensure the safe and effective use of ruxolitinib.

Renal impairment

• In patients with renal impairment, an initial dosage reduction of ruxolitinib may be necessary.
• It is important to avoid using ruxolitinib in patients with end-stage renal disease (ESRD) who do not require dialysis.
• For individuals with myelofibrosis, it is recommended to avoid the use of ruxolitinib if their platelet count is less than 50,000/mm and they have moderate to severe renal impairment.
• Ruxolitinib is not effectively removed by dialysis, although some active metabolites may be eliminated.
• Therefore, on dialysis days, patients should take their ruxolitinib dose after their dialysis session.
• It is crucial to consult with a healthcare professional for appropriate dosage adjustments and to closely monitor renal function in patients receiving ruxolitinib.

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Ruxolitinib: Drug Interaction

Ruxolitinib Drug Interactions Risk Factor C (Monitor therapy)
Ruxolitinib levels may be increased by these drugs	Aprepitant Clofazimine Moderate CYP3A4 Inhibitors Duvelisib Erdafitinib Fosaprepitant Fosnetupitant Larotrectinib Netupitant Palbociclib Simeprevir
The serum concentration of Ruxolitinib may be decreased	Strong CYP3A4 Inducers
The toxic effects of these drugs or Ruxolitinib may be increased when given in combination	Chloramphenicol CloZAPine Denosumab Mesalamine Ocrelizumab Promazine Siponimod Trastuzumab
The therapeutic effects of these drugs may diminish	Pidotimod Tertomotide
The diagnostic efficacy of these tests may diminish	Coccidioides immitis Skin Test

Ruxolitinib Drug Interactions Risk Factor D (Avoid if possible)
Ruxolotinib levels may be increased by these drugs	Strong CYP3A4 Inhibitors Fluconazole MiFEPRIStone Stiripentol
The toxic effects of these drugs or Ruxolitinib may be increased when given in combination	Baricitinib Deferiprone Fingolimod Leflunomide Roflumilast Tofacitinib
The therapeutic effects of these drugs may diminish	Echinacea Nivolumab Sipuleucel-T
The efficacy of vaccines may diminish	Inactivated Vaccines

Ruxolitinib Drug Interactions Risk Factor X (Contraindicated)
Ruxolotinib levels may be increased by these drugs	Conivaptan Fusidic acid Idelalisib
The toxic effects of these drugs or Ruxolitinib may be increased when given in combination	Cladribine Dipyrone Natalizumab Pimecrolimus Tacrolimus Live vaccines
The therapeutic effects of these drugs may diminish	Intravesical BCG

Monitoring parameters:

Complete Blood Count (CBC):

• Perform baseline CBC and monitor every 2 to 4 weeks until dose stabilization.
• Subsequently, monitor as clinically indicated.
• For patients with stage 3 or 4 liver graft-versus-host disease (GVHD), blood counts should be monitored more frequently.

Lipid Parameters:

• Assess lipid parameters 8 to 12 weeks after initiating ruxolitinib and as appropriate thereafter.
• Monitor and manage hyperlipidemia as needed.

Renal Function:

• Monitor renal function in patients with renal impairment.
• Consider initial dosage reduction based on renal function.

Hepatic Function:

• Monitor hepatic function, especially in patients with hepatic impairment.
• Initial dosage reduction may be necessary.

Hepatitis B Viral Load:

• Monitor hepatitis B viral load (HBV-DNA titer) in patients with chronic hepatitis B infection.
• Manage accordingly if changes occur.

Skin Examinations:

• Conduct periodic skin examinations to monitor for non-melanoma skin cancers (basal cell, squamous cell, and Merkel cell carcinoma).

Infection Monitoring:

• Be vigilant for signs and symptoms of infections.
• Utilize appropriate prophylactic antibiotics and promptly treat active infections.

Tuberculin Skin Test:

• Perform a tuberculin skin test prior to initiating ruxolitinib to assess tuberculosis risk factors.

Adherence:

• Monitor patient adherence to the prescribed treatment regimen to ensure optimal therapeutic outcomes.

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How to administer Ruxolitinib (Jakafi)?

Oral Administration:

• Ruxolitinib can be taken orally with or without food.
• If a dose is missed, simply resume the regular dosing schedule and avoid taking an additional dose to make up for the missed one.

Administration via Nasogastric (NG) Tube:

• If a patient is unable to swallow the tablets, ruxolitinib can be administered through a nasogastric (NG) tube with a size of 8 French (≥8 Fr).

Follow these steps for NG tube administration:

• Suspend one tablet in approximately 40 mL of water and stir the mixture for about 10 minutes until the tablet is dispersed.
• Administer the dispersed tablet within 6 hours after preparation using an appropriate syringe.
• After administration, rinse the NG tube with approximately 75 mL of water.

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Mechanism of action of Ruxolitinib (Jakafi):

• Ruxolitinib is a type of medication called a kinase inhibitor. It specifically targets and inhibits two proteins called Janus Associated Kinases (JAKs), namely JAK1 and JAK2. These proteins are involved in signaling pathways that regulate the growth and development of blood cells and immune system function.
• In conditions like myelofibrosis and polycythemia vera, there is an abnormal activity of JAK1/2. Ruxolitinib helps to regulate this activity and bring it back to normal. By doing so, it helps to improve the symptoms associated with these conditions.
• The JAK-STAT signaling pathway plays a role in the development, proliferation, and activation of immune cells that are important in the development of graft-versus-host disease (GVHD). Studies in animals have shown that ruxolitinib may reduce the production of inflammatory substances in the colon and decrease the infiltration of immune cells in the colon, suggesting its potential effectiveness in managing GVHD.
• Ruxolitinib's mechanism of action involves modulating JAK1/2 activity and its effects on the JAK-STAT signaling pathway, which are important for hematopoiesis (blood cell formation) and immune function.

Onset:

• For acute graft-versus-host disease (GVHD), the median time to response with ruxolitinib is around 1.5 weeks, with a range of 1 to 11 weeks (Zeiser 2015).
• In chronic GVHD, the median time to response is approximately 3 weeks, with a range of 1 to 25 weeks (Zeiser 2015). However, responses have been observed within 2 weeks of starting ruxolitinib in some studies (Khoury 2018).

Absorption:

• Ruxolitinib is rapidly absorbed.

Distribution:

• The volume of distribution for ruxolitinib is approximately 72 liters in myelofibrosis and 75 liters in polycythemia vera.

Protein binding:

• Ruxolitinib binds to proteins in the blood, primarily to albumin, at a rate of about 97%.

Metabolism:

• Ruxolitinib is primarily metabolized in the liver, mainly by an enzyme called CYP3A4, and to a lesser extent by CYP2C9.
• The metabolism of ruxolitinib produces active metabolites that account for 20% to 50% of its activity.

Elimination half-life:

• The elimination half-life of ruxolitinib is approximately 3 hours.
• In individuals with hepatic impairment, this may be slightly longer, ranging from 4.1 to 5 hours.
• When considering both ruxolitinib and its metabolites, the overall elimination half-life is around 5.8 hours.

Time to peak concentration:

• Ruxolitinib reaches its peak concentration in the blood within 1 to 2 hours after administration.

Excretion:

• Ruxolitinib and its metabolites are eliminated from the body primarily through urine, accounting for 74% of the dose (less than 1% as an unchanged drug).
• A smaller portion is excreted in feces, amounting to approximately 22% of the dose (again, less than 1% as an unchanged drug).

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International Brand Names of Ruxolitinib:

• Jakafi
• Jakavi

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Ruxolitinib Brand Names in Pakistan:

• Jakafi
• Jakavi