What is extended-release ruxolitinib and how does it differ from the standard pill?
Ruxolitinib is a JAK1/JAK2 inhibitor used to treat myeloproliferative neoplasms (MPNs) like myelofibrosis and polycythemia vera. The standard immediate-release (IR) tablet is taken twice daily, but an extended-release (XR) version is being developed to allow once-daily dosing. The XR formulation releases the drug more slowly, so it stays in your system longer, which is why it can be taken less often.
In a 2025 bioequivalence study, healthy adults received either XR 55 mg once daily or IR 25 mg twice daily for 4 days. The XR form showed a longer half-life (5.4 vs 3.0 hours) and a lower peak concentration (about 25% lower), but the total drug exposure over 24 hours (AUC) was essentially identical—the ratio was 1.008, well within the 0.80–1.25 range that regulators accept for bioequivalence [2]. This means the once-daily pill delivers the same amount of drug to your body over the day, just in a smoother way.
Does once-daily dosing work as well for managing MPNs?
The short answer is: it should, because the drug exposure is the same. The 2025 study confirmed that XR 55 mg once daily matches IR 25 mg twice daily on key measures like area under the curve (AUC) and minimum concentration at steady state [2]. Since the clinical benefits of ruxolitinib—like reducing spleen size and improving symptoms—are tied to drug exposure, the once-daily form is expected to provide the same disease control.
Evidence for ruxolitinib's effectiveness in MPNs comes from studies using the IR form. For example, a 2024 retrospective study of 18 patients found that ruxolitinib reduced spleen volume in 50% of myelofibrosis patients and improved symptoms in 75% [6]. Another 2025 study of 16 patients reported that after 10 years of ruxolitinib, bone marrow fibrosis improved from grade 3 to grade 1 in 6 patients (37.5%) and remained stable in 5 (31.3%) [4]. While these studies used the IR form, the bioequivalence data suggest the XR form would produce similar results.
What are the caveats and risks to consider?
The main caveat is that the XR formulation is new, and long-term safety and effectiveness data in MPN patients are not yet available. The bioequivalence study was done in healthy adults, not in patients, and it only lasted 4 days per treatment [2]. So while the pharmacokinetics look promising, real-world confirmation is still needed.
Another important consideration is infection risk. Ruxolitinib increases the risk of herpes zoster (shingles). A 2022 real-world study found that 19.5% of 128 MPN patients on ruxolitinib developed shingles, an incidence of 68.6 per 1000 person-years—about 7 times higher than in the general population over 50 [1]. A 2021 meta-analysis also found a significantly higher risk of shingles with ruxolitinib (odds ratio 7.39) [3]. This risk applies to both IR and XR forms, so patients should discuss shingles vaccination or antiviral prophylaxis with their doctor.
Additionally, a 2021 study of MPN patients with COVID-19 found that abruptly stopping ruxolitinib at diagnosis was associated with higher mortality (11 out of 45 patients who discontinued died) [5]. This highlights the importance of not stopping ruxolitinib suddenly, regardless of the formulation.
About These Sources
This answer is built on 6 peer-reviewed studies — published from 2021 to 2025, 3 from 2024 or later, 2 in Q1 journals, collectively cited 106 times — selected as the most relevant from 7 studies that passed quality screening, drawn from 55 papers retrieved from a database of over 500 million.
Sources used in this answer
High Incidence of Herpes Zoster in Patients Using Ruxolitinib for Myeloproliferative Neoplasms: Need for Prophylaxis
In a retrospective cohort of 128 MPN patients, 19.5% developed herpes zoster during ruxolitinib treatment, an incidence of 68.6 per 1000 person-years—about 7 times higher than in immunocompetent adults over 50, supporting the need for prophylaxis.
Bioequivalence of ruxolitinib once-daily extended-release vs twice-daily immediate-release tablets in healthy adults
In a randomized crossover study of 169 healthy adults, ruxolitinib XR 55 mg once daily was bioequivalent to IR 25 mg twice daily on AUC and trough concentration, with a 25% lower peak and fewer adverse events (11.8% vs 20.2%).
Effects of ruxolitinib on infection in patients with myeloproliferative neoplasm: a meta-analysis
A meta-analysis of 11 randomized controlled trials found that ruxolitinib increased the risk of herpes zoster (OR 7.39) but did not increase overall infection risk in the early phase; in the extension phase, overall infections were lower with ruxolitinib (OR 0.53).
Significant improvement of bone marrow fibrosis in patients with chronic myeloproliferative neoplasms (CMPN) treated with ruxolitinib.
In a small study of 16 MPN patients, 10 years of ruxolitinib treatment led to a decrease in bone marrow fibrosis grade (from grade 3 to grade 1) in 6 patients (37.5%) and stable disease in 5 (31.3%), with no progression in any patient.
High mortality rate in COVID-19 patients with myeloproliferative neoplasms after abrupt withdrawal of ruxolitinib
In a cohort of 175 MPN patients with COVID-19, mortality was high (48% in myelofibrosis), and abrupt withdrawal of ruxolitinib at COVID-19 diagnosis was associated with increased risk of death (11 of 45 patients who discontinued died).
Is Ruxolitinib an Effective and Safe Therapy for Chronic Myeloproliferative Diseases?
In a retrospective study of 18 MPN patients, ruxolitinib reduced spleen volume in 50% of myelofibrosis patients and improved symptoms in 75%, with no thromboembolic or cardiovascular complications during follow-up.