Jakavi is a prescription oral JAK inhibitor tablet containing Ruxolitinib, indicated for adults with intermediate or high-risk myelofibrosis, polycythemia vera resistant or intolerant to hydroxyurea, and steroid-refractory graft-versus-host disease. Each Jakavi 15mg tablet delivers a measured dose of Ruxolitinib phosphate equivalent to 15mg of Ruxolitinib free base, taken twice daily as directed by a haematologist. Order Jakavi 15mg at PakMeds with a valid specialist prescription.

Jakavi Ingredients and Usage

Jakavi contains Ruxolitinib phosphate, a white to off-white powder with a molecular weight of 404.36. Each tablet includes inactive ingredients: microcrystalline cellulose, lactose monohydrate, magnesium stearate, colloidal silicon dioxide, sodium starch glycolate, povidone, and hydroxypropyl cellulose. Ruxolitinib belongs to the Janus kinase (JAK) inhibitor drug class — specifically a selective oral inhibitor of JAK1 and JAK2 protein kinases. It was first approved by the FDA in November 2011, making it the first therapy approved for intermediate and high-risk myelofibrosis.

Jakavi is indicated for four conditions. First, it treats intermediate or high-risk myelofibrosis (MF) in adults, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. Second, it treats polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea. Third, it treats steroid-refractory acute graft-versus-host disease (aGVHD) in adults and children aged 12 and older. Fourth, it treats chronic graft-versus-host disease (cGVHD) after failure of one or two prior lines of systemic therapy in adults and children aged 12 and older.

The 15mg twice daily dose applies to myelofibrosis patients with a baseline platelet count between 100 and 200 x 10^9/L. Dosing for polycythemia vera starts at 10mg twice daily and can be increased to 25mg twice daily in non-responders with normal blood counts. Jakavi tablets are taken orally with or without food, but must never be taken with grapefruit or grapefruit juice, which significantly increases Ruxolitinib plasma exposure. Jakavi reaches peak plasma concentration within 1 to 2 hours of each dose. It is metabolized via CYP3A4 and CYP2C9 enzymes, with a parent drug half-life of approximately 3 hours.

How Does Jakavi Work?

Janus kinases (JAKs) are intracellular enzymes that attach to cytokine receptors and transmit growth and proliferation signals into the cell nucleus via a pathway called JAK-STAT signalling. In myelofibrosis and polycythemia vera, somatic mutations — most commonly the JAK2V617F mutation — cause constitutive overactivation of JAK1 and JAK2, driving the abnormal production of blood cells, progressive bone marrow fibrosis, and pathological splenomegaly. Ruxolitinib blocks both JAK1 and JAK2 enzymes selectively, interrupting this dysregulated signalling cascade.

By inhibiting JAK1 and JAK2, Jakavi reduces the phosphorylation of STAT proteins and suppresses the downstream gene expression driving myeloproliferative growth. In a preclinical mouse model of JAK2V617F-positive myeloproliferative neoplasm, Ruxolitinib prevented splenomegaly, preferentially reduced JAK2V617F mutant cells in the spleen, and decreased circulating inflammatory cytokines including TNF-alpha and IL-6. In the pivotal Phase 3 COMFORT-I trial, 41.9% of myelofibrosis patients treated with Ruxolitinib achieved a 35% or greater reduction in spleen volume at 24 weeks, compared to just 0.7% of placebo patients. In COMFORT-I, 45.9% of Ruxolitinib patients versus 5.3% of placebo patients achieved a 50% or greater improvement in total symptom score at week 24.

In graft-versus-host disease, JAK-STAT signalling drives the activation of immune cells responsible for attacking the transplant recipient’s tissues. Jakavi suppresses this inflammatory immune activity. In polycythemia vera, Ruxolitinib controls erythrocytosis, reduces thromboembolic risk, and significantly reduces spleen size. In the Phase 3 PV trial, only 1 of 110 patients in the Ruxolitinib arm experienced a thromboembolic event through week 32, compared to 6 of 112 patients in the control arm.

Jakavi Side Effects

Jakavi causes dose-dependent cytopenias — reductions in blood cell counts — as its most clinically significant adverse effect class. Blood counts must be checked before starting Jakavi and regularly throughout treatment. Dose adjustments are commonly required to manage these effects. The most common adverse reactions reported in the COMFORT and PV clinical trials are listed below.

• Thrombocytopenia — low platelet count causing bruising and unusual bleeding, reported in the majority of myelofibrosis patients
• Anaemia — low red blood cell count causing fatigue, pallor, and shortness of breath
• Neutropenia — low white blood cell count increasing infection risk
• Bruising and minor bleeding events
• Dizziness and headache
• Diarrhoea and abdominal discomfort
• Weight gain
• Elevated cholesterol (hypercholesterolaemia) and elevated triglycerides (hypertriglyceridaemia)
• Raised liver enzyme levels (ALT and AST)
• Infections including urinary tract infections, upper respiratory infections, and herpes zoster (shingles) reactivation
• Swelling of the limbs (peripheral oedema) in GVHD patients
• Non-melanoma skin cancers — including basal cell carcinoma — reported in some patients on long-term JAK inhibitor therapy

Warnings

• Myelosuppression and cytopenias: Jakavi causes clinically significant thrombocytopenia, anaemia, and neutropenia. Complete blood counts must be obtained before initiating treatment and monitored regularly. Dose reduction or treatment interruption is required if platelet counts or haemoglobin fall below defined thresholds. Patients with platelet counts below 50 x 10^9/L must not receive Jakavi.
• Serious infections: Jakavi increases the risk of serious bacterial, fungal, viral, and opportunistic infections. Herpes zoster reactivation and dissemination, tuberculosis reactivation, and progressive multifocal leukoencephalopathy (PML) — a potentially fatal brain infection — have been reported. Patients must contact their doctor immediately if they develop fever, chills, sore throat, or signs of infection. Active serious infections must be resolved before starting Jakavi.
• Abrupt discontinuation: Stopping Jakavi suddenly causes rapid return of myelofibrosis symptoms to baseline levels within 1 week, including fever, splenomegaly, and constitutional symptoms. Patients must not stop taking Jakavi without medical guidance. Dose tapering under supervision is recommended.
• Drug interaction — strong CYP3A4 inhibitors: Strong CYP3A4 inhibitors such as ketoconazole increase Ruxolitinib Cmax by 33% and AUC by up to 91%. The starting dose of Jakavi must be reduced to 10mg twice daily when coadministered with strong CYP3A4 inhibitors in patients with platelet counts above 100 x 10^9/L. Jakavi must be avoided in patients on strong CYP3A4 inhibitors with platelet counts below 100 x 10^9/L.
• Drug interaction — strong CYP3A4 inducers: Strong CYP3A4 inducers such as rifampin reduce Ruxolitinib Cmax by 32% and AUC by 61%, substantially reducing therapeutic efficacy. Patients must be closely monitored and dose titrated based on clinical response when these agents are coadministered.
• Drug interaction — fluconazole: Concomitant use of Jakavi with fluconazole doses above 200mg daily must be avoided due to significantly increased Ruxolitinib exposure. If fluconazole at 200mg or below is required, a Jakavi dose reduction is necessary.
• Drug interaction — grapefruit: Jakavi must not be taken with grapefruit or grapefruit juice. Grapefruit inhibits CYP3A4 intestinal metabolism and increases Ruxolitinib exposure, raising the risk of dose-dependent toxicities including severe cytopenias.
• Cardiovascular and thrombotic risk: Based on experience with other JAK inhibitors used in rheumatoid arthritis, there is a possible increased risk of major cardiovascular events (heart attack, stroke) and blood clots in patients with cardiovascular risk factors who smoke or have smoked. Patients with these risk factors should discuss benefit-risk assessment with their prescribing haematologist.
• Non-melanoma skin cancers: Some patients on long-term JAK inhibitor therapy have developed basal cell carcinoma and other non-melanoma skin cancers. Regular skin examination is recommended during prolonged Jakavi treatment.
• Pregnancy: Animal embryofetal studies with Ruxolitinib demonstrated reduced fetal weights and increased late resorptions at maternally toxic doses. There are no adequate studies in pregnant women. Women of childbearing potential must use effective contraception during treatment. Jakavi should only be used in pregnancy if the potential benefit clearly outweighs the risk to the fetus.
• Breastfeeding: Ruxolitinib and its metabolites are excreted in rat milk at concentrations 13 times the maternal plasma level. Women must not breastfeed during Jakavi treatment and for at least 2 weeks after the final dose.
• Renal and hepatic impairment: Dose reductions are required in patients with moderate to severe renal impairment (creatinine clearance 30 to 59 mL/min for PV patients). Patients with any degree of hepatic impairment and platelet counts between 100 and 150 x 10^9/L also require dose reduction. Jakavi should be taken after dialysis in patients on haemodialysis, not before.
• Lactose content: Jakavi tablets contain lactose monohydrate. Patients with rare hereditary conditions of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this product.

Jakavi Storage Conditions

Store Jakavi tablets at room temperature between 20°C and 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F to 86°F). Keep tablets in the original container with the lid tightly closed to protect them from moisture. Do not refrigerate or freeze Jakavi tablets.

Keep Jakavi tablets away from direct sunlight, heat sources, and damp environments such as bathrooms. Store all tablets out of reach of children. Do not use Jakavi past the expiry date printed on the packaging. Dispose of unused or expired tablets as directed by your pharmacist, following applicable cytotoxic or pharmaceutical waste procedures in your region.