RUXOLITINIB Drug Interactions: What You Need to Know

7.

Drug Interactions

Fluconazole: Avoid concomitant use with fluconazole doses greater than 200 mg.

Reduce

Jakafi dosage with fluconazole doses less than or equal to 200 mg. ( 2.6 , 7 ) Strong CYP3A4 Inhibitors: Reduce, interrupt, or discontinue Jakafi 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 Fluconazole Concomitant use of Jakafi 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 with fluconazole doses of greater than 200 mg daily. Reduce the Jakafi 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 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 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 with strong CYP3A4 inducers may decrease ruxolitinib exposure [ see Clinical Pharmacology ( 12.3 )] , which may reduce efficacy of Jakafi. Monitor patients frequently and adjust the Jakafi dose based on safety and efficacy [ see Clinical Pharmacology ( 12.3 )] .

4.

Contraindications

None. None. ( 4 )

5.

Warnings And Precautions

Thrombocytopenia, Anemia and Neutropenia: Manage by dose reduction, or interruption, or transfusion. ( 5.1 ) Risk of Infection: Assess patients for signs and symptoms of infection and initiate appropriate treatment promptly. Serious infections should have resolved before starting therapy with Jakafi. ( 5.2 )

Symptom Exacerbation Following

Interruption or Discontinuation: Manage with supportive care and consider resuming treatment with Jakafi. ( 5.3 ) Risk of Non-Melanoma Skin Cancer: Perform periodic skin examinations. ( 5.4 )

Lipid

Elevations: Assess lipid levels 8-12 weeks from start of therapy and treat as needed. ( 5.5 )

Major Adverse Cardiovascular

Events (MACE): Monitor for development of MACE. ( 5.6 ) Thrombosis: Evaluate and treat symptoms of thrombosis promptly. ( 5.7 )

Secondary

Malignancies: Monitor for development of secondary malignancies, particularly in patients who are current or past smokers. ( 5.8 )

5.1 Thrombocytopenia, Anemia and Neutropenia Treatment with Jakafi can cause thrombocytopenia, anemia and neutropenia [ see Adverse Reactions ( 6.1 )] . Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet transfusions may be necessary [ see Dosage and Administration ( 2 ) ] . Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi. Severe neutropenia (ANC less than 0.5 × 10 9 /L) was generally reversible by withholding Jakafi until recovery. Perform a pre-treatment complete blood count (CBC) and monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated [ see Dosage and Administration ( 2 )] .

5.2 Risk of Infection Serious bacterial, mycobacterial, fungal and viral infections have occurred [ see Adverse Reactions ( 6.1 )] . Delay starting therapy with Jakafi until active serious infections have resolved. Observe patients receiving Jakafi for signs and symptoms of infection and manage promptly. Use active surveillance and prophylactic antibiotics according to clinical guidelines.

Tuberculosis

Tuberculosis infection has been reported in patients receiving Jakafi. Observe patients receiving Jakafi for signs and symptoms of active tuberculosis and manage promptly. Prior to initiating Jakafi, patients should be evaluated for tuberculosis 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. For patients with evidence of active or latent tuberculosis, consult a physician with expertise in the treatment of tuberculosis before starting Jakafi. The decision to continue Jakafi during treatment of active tuberculosis should be based on the overall risk-benefit determination.

Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is suspected, stop Jakafi and evaluate.

Herpes

Zoster and Herpes Simplex Herpes zoster infection has been reported in patients receiving Jakafi [see Adverse Reactions ( 6.1 )] . Advise patients about early signs and symptoms of herpes zoster and to seek treatment as early as possible if suspected. Herpes simplex virus reactivation and/or dissemination has been reported in patients receiving Jakafi [see Adverse Reactions ( 6.2 )] . Monitor patients for the development of herpes simplex infections. If a patient develops evidence of dissemination of herpes simplex, consider interrupting treatment with Jakafi; patients should be promptly treated and monitored according to clinical guidelines. Hepatitis B Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations in alanine aminotransferase and aspartate aminotransferase, have been reported in patients with chronic HBV infections taking Jakafi. The effect of Jakafi on viral replication in patients with chronic HBV infection is unknown. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines.

5.3 Symptom Exacerbation Following Interruption or Discontinuation of Treatment with Jakafi Following discontinuation of Jakafi, symptoms from myeloproliferative neoplasms may return to pretreatment levels over a period of approximately one week. Some patients with MF have experienced one or more of the following adverse events after discontinuing Jakafi: fever, respiratory distress, hypotension, DIC, or multi-organ failure. If one or more of these occur after discontinuation of, or while tapering the dose of Jakafi, evaluate for and treat any intercurrent illness and consider restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi therapy without consulting their physician. When discontinuing or interrupting therapy with Jakafi for reasons other than thrombocytopenia or neutropenia <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.8 )]</span> , consider tapering the dose of Jakafi gradually rather than discontinuing abruptly.

5.4 Non-Melanoma Skin Cancer (NMSC) Non-melanoma skin cancers including basal cell, squamous cell, and Merkel cell carcinoma have occurred in patients treated with Jakafi. Perform periodic skin examinations.

5.5 Lipid Elevations Treatment with Jakafi has been associated with increases in lipid parameters including total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> . The effect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined in patients treated with Jakafi. Assess lipid parameters approximately 8-12 weeks following initiation of Jakafi therapy. Monitor and treat according to clinical guidelines for the management of hyperlipidemia.

5.6 Major Adverse Cardiovascular Events (MACE) Another JAK-inhibitor has increased the risk of MACE, including cardiovascular death, myocardial infarction, and stroke (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi particularly in patients who are current or past smokers and patients with other cardiovascular risk factors. Patients should be informed about the symptoms of serious cardiovascular events and the steps to take if they occur.

5.7 Thrombosis Another JAK-inhibitor has increased the 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 Jakafi is not indicated. In patients with MF and PV treated with Jakafi in clinical trials, the rates of thromboembolic events were similar in Jakafi and control treated patients. Patients with symptoms of thrombosis should be promptly evaluated and treated appropriately.

5.8 Secondary Malignancies Another JAK-inhibitor has increased the 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 the benefits and risks for the individual patient prior to initiating or continuing therapy with Jakafi, 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.