Ruxolitinib

Ruxolitinib is a prescription medicine used to treat the symptoms of acute graft versus host disease (GVHD), polycythemia vera, and myelofibrosis (MF).

• Ruxolitinib is available under the following different brand names: Jakafi

Adult and pediatric dosage

Tablet

• 5mg
• 10mg
• 15mg
• 20mg
• 25mg

Myelofibrosis

Adult dosage

• Initial dose
  • Platelet count more than 200 x109/L: 20 mg orally twice a day
  • Platelet count 100-200 x109/L: 15 mg orally twice a day
  • Platelet count 50 to less than 100 x109/L: 5 mg orally twice a day
  • Insufficient response for patients starting treatment with a platelet count of more than 100 X 10^9/L
  • If the response is insufficient and platelet count and ANC are adequate, the dose may be increased to 5 mg twice a day increments; not to exceed 25 mg orally twice a day
  • Do not increase the dose during the first 4 weeks of therapy and no more frequently than every 2 Weeks

Polycythemia Vera

Adult dosage

• Initial: 10 mg orally twice a day
  • Increasing dose for insufficient response
  • If the response is insufficient and platelet, hemoglobin, and neutrophil counts are adequate, doses may be increased in 5 mg twice a day increments to a maximum of 25 mg twice a day
  • Doses should not be increased during the first 4 weeks of therapy and not more frequently than every 2 Weeks

Acute Graft versus Host Disease

Adult dosage

• Initial dose: 5 mg orally twice a day; may increase to 10 mg twice a day after at least 3 days if ANC and platelet counts have not decreased by more than 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 approximately every 8 Weeks (eg, 10 mg twice a day to 5 mg once daily)
• Patients unable to tolerate 5 mg once daily: Interrupt treatment until clinical and/or laboratory parameters recover

Pediatric dosage

• Children below 12 years: Safety and efficacy not established
• Children above 12 years: 
• Initial dose: 5 mg orally twice a day; may increase to 10 mg twice a day after at least 3 days if ANC and platelet counts have not decreased by more than 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 approximately every 8 Weeks (eg, 10 mg twice a day to 5 mg twice a day to 5 mg once daily)
• Patients unable to tolerate 5 mg once daily: Interrupt treatment until clinical and/or laboratory parameters recover
• If acute GVHD signs or symptoms recur during or after the taper, consider retreatment

Chronic Graft versus Host Disease

Adult dosage

• Initial dose: 10 mg orally twice a day
• Consider tapering after 6 months in patients with response who have discontinued therapeutic doses of corticosteroids

Tapering dose

• Taper by 1 dose level approximately every 8 Weeks (eg, 10 mg twice a day to 5 mg twice a day, then from 5 mg twice a day to 5 mg once daily)
• If acute GVHD signs or symptoms recur during or after the taper, consider retreatment

Pediatric dosage

• Children below 12 years: Safety and efficacy not established
• Children above 12 years: 
• dose: 10 mg orally twice a day
• Consider tapering after 6 months in patients with response who have discontinued therapeutic doses of corticosteroids

Tapering dose

• Taper by 1 dose level approximately every 8 Weeks (eg, 10 mg twice a day to 5 mg twice a day, then from 5 mg twice a day to 5 mg once daily)
• If acute GVHD signs or symptoms recur during or after the taper, consider retreatment

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Ruxolitinib include:

• anemia,
• easy bruising,
• dizziness, and
• headache.

Serious side effects of Ruxolitinib include:

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• blisters or painful skin rash,
• changes in the size, shape, or color of a mole or skin lesion,
• problems with speech thought, vision, or muscle movement,
• nausea,
• vomiting,
• weakness,
• general ill feeling,
• pain or burning when urinating,
• fever,
• chills,
• tiredness,
• mouth sores,
• skin sores,
• easy bruising,
• unusual bleeding,
• pale skin,
• cold hands and feet,
• lightheadedness,
• shortness of breath,
• cough,
• night sweats,
• loss of appetite,
• weight loss, and
• feeling very tired.

Rare side effect of Ruxolitinib include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Ruxolitinib has severe interactions with no other drugs.
• Ruxolitinib has serious interactions with at least 35 other drugs.
• Ruxolitinib has moderate interactions with at least 54 other drugs.
• Ruxolitinib has minor interactions with at least 99 other drugs. 

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Ruxolitinib?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Ruxolitinib?”

Cautions

• Nonmelanoma skin cancers were reported 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 less than 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 the 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 below 0.5 x109/L) was generally reversible and was managed by temporarily withholding the dose
• Infections
  • Assess for the risk of developing serious bacterial, mycobacterial, fungal, and viral infections
  • Active serious infections should have been 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 an 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 them to seek treatment as early as possible
  • Progressive multifocal leukoencephalopathy (PML): Reported with ruxolitinib treatment for myelofibrosis; if suspected, discontinue the 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 a 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 increasing 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; monitoring according to clinical guidelines for the 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 patients before 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 an 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 an 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 the individual patient before 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 by 33% and 91%, respectively
    • Dose modification is 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 and Lactation

• When pregnant rats and rabbits were administered ruxolitinib during organogenesis adverse developmental outcomes occurred at doses associated with maternal toxicity
• There are no studies on 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 breastfed 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 the final dose