LuciRux

Ruxolitinib (Jakavi) instructions
Common name: Ruxolitinib
Trade name: Jakavi, Jakafi
Full names: Ruxolitinib, Ruxolitinib, Ruxolitinib, Ruxolitinib, Jakavi, Jakafi, Ruxolitinib

Indications:
Ruxolitinib is suitable for the treatment of intermediate-risk or high-risk myelofibrosis, Includes patients with primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis.

Usage and dosage:
Myelofibrosis
Adults, take orally once every 12 hours, twice daily, as indicated. The dosage of luxolitinib is generally between 5 mg and 25 mg, and should be increased or decreased according to the patient's condition.

Polycythemia vera
Adults, 10 mg orally once daily, every 12 hours, as indicated. It should be increased or decreased according to the patient's condition, but it should not exceed 25 mg twice a day.

Adverse reactions:
> 10% (MF and PV)
Anemia (96.1%)
Thrombocytopenia (69.7%)
Increased ALT, grade 1 (25.2%)
Contusion (23.2%)
Neutropenia Symptoms (18.7%)
Dizziness (18.1%)
AST upgrade, grade 1 (17.1%)
Increased cholesterol, grade 1 (16.8%)
Headache (14.8%)

> 10% (GvHD)
Anemia (75%)
Thrombocytopenia (75%)
Thrombocytopenia, grade 3-4 (61%)
Neutropenia (58%)
Infection (55% )
Edema (51%)
Hemorrhage (49%)
Anemia, grade 3-4 (45%)
Infection, grade 3-4 (41%)
Neutropenia (40%)
Elevated ALT / AST (48%)
Fatigue (37%)
Bacterial infection (32%)
Bacterial infection grade 3-4 (28%)
Bleeding, grade 3-4 (20%)
Fatigue, grade 3-4 (14%)
Grade 3-4 edema (13%)
Hypertriglyceridemia (11%)

1-10% (MF and PV)
Urinary tract infection (9%)
Weight gain (7.1%)
Flatulence (5.2%)
Herpes zoster (1.9%)
Increased ALT, grade 2 (1.9%)
Increased ALT, grade 3 (1.3%)

1-10% (GvHD)
Elevated ALT / AST, Grade 3-4 (6-8%)
Hypertriglyceridemia, Grade 3-4 (1%)

<1%
AST, Grade 2 increased (0.6%)
Cholesterol increased, Grade 2 (0.6%)

Contraindications:
None

Precautions:
Thrombocytopenia, anemia and neutropenia
Obtain a CBC before initiating treatment and monitor as clinically indicated and adjust dose as needed.
Patients with platelet counts <200 x10^9/L at the start of treatment are more likely to develop thrombocytopenia during treatment.
Thrombocytopenia is usually reversible and is usually managed by dose reduction or temporary dose withholding (see Adult Dosage); platelet transfusions may be given if clinically indicated.
Anemia may require blood transfusion; dose modification may also be considered.
Neutropenia (ANC <0.5×10^9/L) is usually reversible and controlled by temporary discontinuation of dosing.

Infections
Assess the risk of developing serious bacterial, mycobacterial, fungal and viral infections.
Positive feelings of severity should have been resolved before starting treatment.
Tuberculosis (TB) infection has been reported; before initiation, assess patients for TB risk factors and test for latent infection in those at higher risk.

Watch patients carefully for signs and symptoms of infection and initiate appropriate treatment immediately.
Herpes zoster: Inform patients of the early signs and symptoms of herpes zoster and advise to seek treatment as early as possible
Progressive multifocal leukoencephalopathy (PML): Treat myelofibrosis with ruxolitinib; if suspected, discontinue drug and evaluate
Hepatitis B viral load (HBV-DNA titer) increases, with or without associated elevations of alanine aminotransferase and aspartate aminotransferase reported in patients with chronic HBV infection; The effect of ruxolitinib on viral replication is unknown; treat and monitor patients with chronic HBV infection according to clinical guidelines.

Symptoms of dose interruption, dose tapering, or discontinuation
After discontinuation/interruption, myelofibrosis symptoms may worsen and return to pretreatment levels after 1 week
Other adverse reactions reported include fever, respiratory distress, hypotension, DIC, or multiorgan failure
If these symptoms occur after discontinuation or dose tapering , please evaluate and treat any concurrent disease and consider restarting ruxolitinib or increasing the dose
Instruct patients not to interrupt or discontinue ruxolitinib without consulting their physician
When treatment is discontinued or interrupted for reasons other than thrombocytopenia or neutropenia, consider a gradual dose reduction rather than abrupt discontinuation.

Hyperlipidemia
Treatment is associated with increases in lipid parameters, including total cholesterol, low-density lipoprotein, and triglycerides; assess lipid parameters approximately 8-12 weeks after initiation of treatment; monitor according to clinical guidelines for hyperlipidemia.

Storage:
Tablets: Store at room temperature 20-25°C (68-77°F); excursions 15-30°C (59-86°F)
Suspension in NG tubes: Store at room temperature 20-25°C (68-77°F) for up to 6 hours.

Mechanism of action:
CYP3A4 inhibitor
Ruxolitinib is mainly metabolized by CYP3A4.
Strong CYP3A4 inhibitors increased ruxolitinib Cmax and AUC by 33% and 91%, respectively.
Recommended dose adjustments 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 reduce ruxolitinib exposure.

Efficacy and Safety:
Novartis announced positive data from the pivotal Phase III RESPONSE study of the anti-cancer drug Jakavi (ruxilitinib) on June 3. RESPONSE is a global, randomized, open-label study conducted at 109 sites worldwide. In the trial, 222 patients with polycythemia vera (PV) who were resistant or intolerant to hydroxyurea were randomized to receive ruxolitinib (10 mg twice daily) or optimal therapy (i.e., monotherapy selected by the investigators or observation alone). Doses were adjusted as needed throughout the study. The primary endpoints were the proportion of patients with hematocrit control without the need for phlebotomy and a reduction in spleen volume of 35% or more from baseline at 32 weeks (assessed by imaging). In addition to safety, key secondary endpoints include durable response and complete hematologic response.
Results show that the study met its primary endpoint of maintaining hematocrit (volume of red blood cells) under control without the need for phlebotomy (a procedure in which some blood is removed from the body to reduce red blood cell concentration) while reducing spleen size in patients with polycythemia vera who are resistant or intolerant to hydroxyurea. Seventy percent of patients in the Jakavi group achieved hematocrit control or reduced spleen volume, compared with 20% in the best supportive care group. The safety profile of ruxolitinib in the study was consistent with previous studies.