Zylexx 75Mg Tab 20 s Potential Overview:

• Brand Name: Zylexx
• Generic Name: Ruxolitinib
• Strength: 75 mg
• Formulation: Tablet
• Pack Size: 20 Tablets

1. Mechanism of Action (MOA):

• Zylexx contains the active ingredient Ruxolitinib, a Janus Kinase (JAK) inhibitor.
• Ruxolitinib selectively inhibits JAK1 and JAK2, enzymes that are involved in the signaling pathways of several key cytokines and growth factors, which are critical for regulating immune responses and hematopoiesis (blood cell production).
• By inhibiting JAK1 and JAK2, Zylexx modulates immune function and reduces inflammation, making it effective in treating conditions such as myelofibrosis and polycythemia vera, where there is abnormal blood cell production and immune activation.

2. Indications:

Zylexx (Ruxolitinib 75 mg) is indicated for the treatment of the following conditions:

• Myelofibrosis (MF): A type of bone marrow cancer characterized by the formation of scar tissue in the bone marrow, which disrupts normal blood cell production.
• Polycythemia Vera (PV): A myeloproliferative disorder where the bone marrow produces too many red blood cells, increasing blood viscosity and the risk of thrombosis.
• Graft-Versus-Host Disease (GVHD): A complication following a stem cell or bone marrow transplant, where the donor’s immune cells attack the recipient’s tissues. Zylexx is used in steroid-refractory cases of GVHD.

3. Dosage:

• Initial Dose:
  • Myelofibrosis: The typical starting dose of Zylexx (Ruxolitinib) is 20 mg twice daily for patients with normal liver function. For patients with renal impairment, the starting dose may be adjusted to 15 mg twice daily.
  • Polycythemia Vera: The starting dose is usually 10 mg twice daily, adjusted depending on response and tolerability.
  • Graft-Versus-Host Disease (GVHD): The typical starting dose is 5 mg twice daily, with dose adjustments based on patient response.
• Dosage Adjustments:
  • Renal Impairment: In patients with moderate to severe renal dysfunction, the dose should be reduced.
  • Hepatic Impairment: Dose adjustments are necessary for patients with hepatic impairment (especially Child-Pugh Class B or C).
• Administration:
  • Zylexx should be taken orally, with or without food. It is advised to take it at the same time every day.
  • Swallow tablets whole; do not crush or chew.

4. Side Effects:

Common side effects of Zylexx (Ruxolitinib) include:

• Anemia: Decreased red blood cell count leading to fatigue, dizziness, and weakness.
• Thrombocytopenia: Low platelet count, which increases the risk of bleeding and bruising.
• Headache.
• Diarrhea, nausea, or constipation.
• Elevated liver enzymes (indicative of liver stress).

Serious side effects:

• Infections: Increased risk of serious bacterial, viral, or fungal infections due to immune suppression.
• Bone marrow suppression: Neutropenia (low white blood cell count) and thrombocytopenia can lead to increased risk of infections and bleeding.
• Liver toxicity: Hepatic impairment can occur; liver function tests should be monitored.
• Tumor Lysis Syndrome: Rare but can occur with the rapid breakdown of cancer cells.
• Skin cancers: Long-term use may increase the risk of non-melanoma skin cancer.

5. Precautions:

• Infections: Ruxolitinib suppresses the immune system, increasing the risk of serious infections such as tuberculosis, pneumonia, and fungal infections. Screen for tuberculosis before starting treatment and consider prophylactic treatment for TB-positive patients.
• Bone marrow suppression: Ruxolitinib can cause anemia, thrombocytopenia, and neutropenia, so it is important to monitor blood counts regularly during treatment.
• Liver function: Monitor liver function tests regularly. Dose reductions are required if there is evidence of liver toxicity.
• Renal impairment: Use with caution in patients with moderate-to-severe renal dysfunction. Dose adjustments may be necessary in such cases.
• Vaccinations: Live vaccines should be avoided during treatment with Ruxolitinib due to the risk of immune suppression and reduced vaccine efficacy.
• Cancer risk: There is an increased risk of skin cancers (e.g., non-melanoma skin cancer) with prolonged use. Patients should undergo regular dermatological checks.
• Pregnancy and Lactation:
  • Pregnancy: Zylexx is Category C in pregnancy, meaning it should only be used if the potential benefits outweigh the risks. It should not be used in pregnancy unless absolutely necessary.
  • Breastfeeding: It is not recommended to breastfeed while taking Ruxolitinib, as it may pass into breast milk and affect the infant.

6. Contraindications (CI):

Zylexx (Ruxolitinib) is contraindicated in the following situations:

• Hypersensitivity: Known allergy or hypersensitivity to Ruxolitinib or any of the tablet’s components.
• Active Infections: Contraindicated in patients with active systemic infections, such as bacterial, viral, or fungal infections.
• Severe Hepatic Impairment: Contraindicated in patients with severe liver impairment (e.g., Child-Pugh Class C).

Pharmacist Related Data

Chemical Formula:

• Chemical Name: (2S)-1-[(4-Methyl-2-pyrimidinyl)methyl]-3-(pyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine
• Molecular Formula: C17H18N6
• Molecular Weight: 306.37 g/mol

Half-Life:

• Terminal Half-Life: Approximately 3 hours.
  • This is the time it takes for the concentration of the drug in the bloodstream to decrease by half after the administration of a dose.

Metabolism:

• Ruxolitinib is primarily metabolized by the liver through the cytochrome P450 enzyme system, specifically CYP3A4 and CYP3A5.
• The drug undergoes oxidation and N-demethylation to form inactive metabolites, with the major metabolite being M19, which has no known pharmacological activity.
• Excretion: Ruxolitinib is eliminated primarily through feces (around 74% of the dose), with a smaller amount eliminated in the urine (around 22%).

Drug Interactions:

Drug Interactions with Medicines:

1. CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole, ritonavir, clarithromycin):
   • May increase Ruxolitinib concentrations. Dose reduction of Ruxolitinib may be necessary when used together with strong CYP3A4 inhibitors.
2. CYP3A4 Inducers (e.g., rifampin, carbamazepine, phenytoin):
   • May decrease Ruxolitinib concentrations, potentially reducing its efficacy. Close monitoring of therapeutic effect and dose adjustments may be needed.
3. Anticoagulants (e.g., warfarin, dabigatran, clopidogrel):
   • Ruxolitinib may increase the risk of bleeding when used with anticoagulants or antiplatelet agents. Close monitoring of bleeding risks is essential.
4. Immunosuppressants (e.g., cyclosporine, tacrolimus):
   • Ruxolitinib may enhance the immunosuppressive effects of other immunosuppressive agents, increasing the risk of infections. Monitor for signs of infection.
5. Live Vaccines:
   • Live vaccines should be avoided during treatment with Ruxolitinib due to the immune suppression it causes, which can interfere with the immune system’s response to the vaccine.

Drug Interactions with Food:

• Food: No significant food interactions have been identified with Ruxolitinib. The drug can be taken with or without food.
• Grapefruit: Grapefruit and grapefruit juice may increase the plasma concentration of Ruxolitinib because of CYP3A4 inhibition. Patients should avoid consuming grapefruit while on this medication.

Pharmacodynamics:

• Ruxolitinib is a Janus Kinase (JAK) inhibitor that selectively inhibits JAK1 and JAK2 enzymes, which are involved in cytokine signaling.
• By inhibiting JAK1 and JAK2, Ruxolitinib interferes with the signaling pathways that regulate immune responses and hematopoiesis (blood cell production).
• This inhibition leads to:
  • Reduction in inflammation by decreasing the activity of inflammatory cytokines.
  • Control of abnormal blood cell production, helping manage diseases like myelofibrosis and polycythemia vera, where overproduction of blood cells occurs.
• Zylexx improves splenomegaly, pruritus, fatigue, and anemia, which are common symptoms of these disorders.
• It also helps manage graft-vs-host disease (GVHD), where it reduces immune-mediated damage to the recipient’s tissues after a stem cell or bone marrow transplant.

Pharmacokinetics:

• Absorption:
  • Ruxolitinib is well absorbed after oral administration, with peak plasma concentrations occurring in 2 hours.
  • Bioavailability is approximately 95%.
• Distribution:
  • It is extensively protein-bound (about 97% bound to plasma proteins, mainly albumin).
  • The volume of distribution (Vd) is large (~ 100 L), indicating extensive tissue distribution.
• Metabolism:
  • Ruxolitinib is metabolized by CYP3A4 and CYP3A5 enzymes in the liver. It is converted into inactive metabolites.
  • The primary metabolite (M19) has no known pharmacologic activity.
• Excretion:
  • About 74% of the drug is eliminated in the feces, while 22% is excreted in urine.
  • The remaining drug and its metabolites are excreted through other routes, such as bile.
• Half-life:
  • The half-life of Ruxolitinib is approximately 3 hours.
• Steady-State:
  • Steady-state concentrations are generally reached after 3 to 5 days of regular dosing.