Ruxolitinib
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| Non-proprietary name | Ruxolitinib | ||||||||||||
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(3 R ) -3-cyclopentyl-3- [4- (7 H -pyrrolo [2,3- d ] pyrimidin-4-yl) pyrazol-1-yl] propanenitrile ( IUPAC ) |
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| Molecular formula | C 17 H 18 N 6 | ||||||||||||
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| Molar mass | 306.37 g mol −1 | ||||||||||||
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | |||||||||||||
Ruxolitinib is an enzyme inhibitor ( tyrosine kinase inhibitor ) that is used in certain blood formation diseases ( myeloproliferative neoplasias ) such as idiopathic (or primary) myelofibrosis or polycythemia . The active ingredient is approved since 2012 (trade names Jakafi , Jakavi ) and selectively inhibits the two Janus kinases JAK-1 and JAK-2, which via the JAK-STAT signaling pathway, the effect of pro-inflammatory mediators and cytokines , eg. B. mediate interferon-γ in the cell and the cell nucleus .
indication
The use of ruxolitinib is indicated in the treatment of primary myelofibrosis, polycythemia vera and in post- essential thrombocythemia myelofibrosis or post polycythemia vera myelofibrosis .
Ruxolitinib also shows good results in the treatment of the acute and cortisone- refractory graft-versus-host reaction , i.e. an immune reaction of the stem cells after allogeneic stem cell transplantation against the recipient. In an open, randomized controlled study (phase III study), 62% of the patients treated with ruxolitinib (versus 39% in the control group) showed a reaction ( odds ratio 2.64) with a median survival time of 11 months (versus 7 Months). Ruxolitinib has not yet been approved for this indication.
Contraindications
If the platelet count falls below 50,000 / µl or the leukocyte count is <500 / µl, the treatment should be interrupted. In addition, pregnancy and breastfeeding are contraindications.
Some patients with myelofibrosis develop aggressive B-cell lymphoma two to three years after the start of therapy, as JAK2 inhibitors activate dormant B-cell lymphomas in the bone marrow and thus trigger the cancer. Aggressive lymphoma slumbers in around 16 percent of myelofibrosis patients. In about six percent of these, it breaks out through JAK-2 inhibitors. The dormant lymphomas can, if one is looking for them, be discovered by a sensitive, molecular biological method - in order to protect risk patients from therapy with JAK2 inhibitors.
Dose adjustment
In severe renal impairment with creatinine clearance <30 ml / min, the dose should be halved.
Side effects
The most common side effects include dizziness and headache. Infections and an increase in blood pressure were also more common during treatment than in placebo-treated patients.
Dose-dependent undesirable "on-target" effects are anemia , blood platelet deficiency ( thrombocytopenia ), a reduced number of white blood cells and bleeding, and immunosuppression . Also cytomegalovirus -Reaktivierungen were frequently observed. Ruxolitinib appears to be a very selective inhibitor with few "off-target" effects
Use with CoViD-19
Ruxolitinib has been used experimentally and apparently successfully against CoViD-19 .
Individual evidence
- ↑ a b ruxolitinib . (PDF; 30 kB) caymanchem; Retrieved July 11, 2016.
- ^ LP Yang, GM Keating: Ruxolitinib: in the treatment of myelofibrosis. In: Drugs. Volume 72, Number 16, November 2012, pp. 2117-2127, PMID 23061804 .
- ^ C. Keohane, DH Radia, CN Harrison: Treatment and management of myelofibrosis in the era of JAK inhibitors. In: Biologics: targets & therapy. Volume 7, 2013, pp. 189-198, doi: 10.2147 / BTT.S34942 , PMID 23990704 , PMC 3753053 (free full text).
- Jump up ↑ Robert Zeiser, Nikolas von Bubnoff, Jason Butler, Mohamad Mohty, Dietger Niederwieser, Reuven Or, Jeff Szer, Eva M. Wagner, Tsila Zuckerman, Bruyère Mahuzier, Judith Xu, Celine Wilke, Kunal K. Gandhi, Gérard Socié et al. for the "REACH2 Trial Group": Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease . New England Journal of Medicine 2020, Volume 382, Issue 19, May 7, 2020, pages 1800-1810, DOI: 10.1056 / NEJMoa1917635
- ↑ bloodjournal.org E. Porpaczy et al .: Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1 / 2 inhibitor therapy. In: Blood , doi: 10.1182 / blood-2017-10-810739 .
- ↑ M. Kogler: Ruxolitinib in the treatment of chronic idiopathic myelofibrosis. Clinic and Research 2013; 19.1; 67.
- ↑ Y. Ogama, T. Mineyama, A. Yamamoto, M. Woo, N. Shimada, T. Amagasaki, K. Natsume: A randomized dose-escalation study to assess the safety, tolerability, and pharmacokinetics of ruxolitinib (INC424) in healthy Japanese volunteers . In: International Journal of Hematology . tape 97 , no. 3 , 2013, p. 351-359 , doi : 10.1007 / s12185-013-1280-5 , PMID 23381973 .
- ↑ Nelson Chao: Finally, a Successful Randomized Trial for GVHD New England Journal of Medicine 2020, Volume 382, Issue 19 of May 7, 2020, pages 1853-1854, DOI: 10.1056 / NEJMe2003331
- ↑ Cancer drug cures COVID-19 patient from lung failure. Retrieved June 18, 2020 .
- ↑ Andreas Neubauer, Thomas Wiesmann, Claus F. Vogelmeier, Elisabeth Mack, Chrysanthi Skevaki: Ruxolitinib for the treatment of SARS-CoV-2 induced acute respiratory distress syndrome (ARDS) . In: Leukemia . June 17, 2020, ISSN 1476-5551 , p. 1–3 , doi : 10.1038 / s41375-020-0907-9 ( nature.com [accessed June 18, 2020]).
