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Lung Cancer (Amsterdam, Netherlands) Aug 2020Immune checkpoint inhibitors (ICIs) have shown antitumor activity against a wide variety of malignancies. ICI-induced immune-related thrombocytopenia is a rare...
OBJECTIVES
Immune checkpoint inhibitors (ICIs) have shown antitumor activity against a wide variety of malignancies. ICI-induced immune-related thrombocytopenia is a rare immune-related adverse event (irAE). Little is known about the treatment of refractory immune-related thrombocytopenia in non-small cell lung cancer (NSCLC) patients treated with pembrolizumab.
RESULTS
We report the case of a patient with advanced NSCLC complicated by pembrolizumab-induced refractory immune-related thrombocytopenia who showed remarkable improvement in the thrombocytopenia in response to eltrombopag olamine treatment.
CONCLUSION
Eltrombopag olamine can be a viable treatment option for refractory pembrolizumab-induced immune-related thrombocytopenia in an NSCLC patient.
Topics: Antibodies, Monoclonal, Humanized; Benzoates; Carcinoma, Non-Small-Cell Lung; Humans; Hydrazines; Lung Neoplasms; Pyrazoles; Thrombocytopenia
PubMed: 32505447
DOI: 10.1016/j.lungcan.2020.05.015 -
Journal of Pharmaceutical and... Sep 2021Eltrombopag olamine is prescribed for chronic immune (idiopathic) thrombocytopenic purpura (ITP). This work aims to investigate the formation of potential degradants of...
Eltrombopag olamine is prescribed for chronic immune (idiopathic) thrombocytopenic purpura (ITP). This work aims to investigate the formation of potential degradants of the drug and determine their toxicity in silico. A stability-indicating high performance liquid chromatography (HPLC) method was developed to separate six oxidative degradation impurities and three thermal degradation impurities employing the quality by design (QBD) approach. The degradation impurities were resolved with minimum resolution of 1.5 using a phenyl column with 0.1 % trifluoroacetic acid (TFA) and acetonitrile as the mobile phase and quantified at 245 nm. The structure and degradation pathway for the degradants was proposed by employing liquid chromatography with tandem mass spectrometry (LC-MS/MS), among the identified degradation pathways demethylation and decarboxylation are common reactions observed during oxidation resulted in majority of degradation products. All the degradation products are characterized with help of the daughter ions and product ion obtained upon LC-MS/MS analysis. The HPLC method parameters such as column temperature, flow rate, TFA concentration and organic concentration are identified as critical method attributes (CMA), a design of experiments (DOE) mediated design space was established through use of design experts. The resolution between sets of adjacent peaks was identified as a critical quality attribute; among the investigated CMAs, column temperature and flow rate significantly affected the resolution. Furthermore, the toxicology of the degradation products was predicted with the help of in silico TOPKAT analysis, the carcinogenicity of the impurities was discussed.
Topics: Benzoates; Chromatography, High Pressure Liquid; Chromatography, Liquid; Computer Simulation; Drug Contamination; Drug Stability; Hydrazines; Pyrazoles; Tandem Mass Spectrometry
PubMed: 34225039
DOI: 10.1016/j.jpba.2021.114231 -
Journal of AOAC International Mar 2023A simple and reliable HPLC method for determining impurities in eltrombopag olamine (ELO) film-coated tablets is not available. At the same time, there is no official...
Stability-Indicating RP-HPLC Method Development and Validation for Eltrombopag Olamine in the Presence of Impurities and Degradation Products. Robustness by Design of Expert Software.
BACKGROUND
A simple and reliable HPLC method for determining impurities in eltrombopag olamine (ELO) film-coated tablets is not available. At the same time, there is no official monograph reported. The proposed research is targeted at the development of a stability-indicating method for determining impurities in ELO film-coated tablets and drug substances.
OBJECTIVE
To develop and validate a simple and effective HPLC method for determining impurities in ELO film-coated tablets and drug substances.
METHODS
All the impurities were separated using a reverse phase (RP)-HPLC system equipped with a Zorbax SB-Phenyl 150 mm × 4.6 mm, 3.5 µm, column with UV detection at 230 nm and a flow rate of 1.2 mL/min. The column temperature was maintained at 45°C.
RESULTS
The proposed method was validated as per current regulatory guidelines. The coefficient of correlation was found to be >0.999 for all impurities. The LOD and LOQ for ELO and all specified impurities were determined. The precision and accuracy were obtained for ELO and its related impurities. Intra- and inter-day RSD values were between 1.22 and 2.04%, and impurity recovery varied between 93.80 and 103.69%. The stability of standard and sample solutions was established for 24 h.
CONCLUSIONS
As per recent guidelines, a stability-indicating method has been developed to determine the impurities in ELO film-coated tablets and drug substances. QbD-based robustness was performed and proved that the method was robust.
HIGHLIGHTS
The proposed article is the first RP-HPLC method for determining impurities in ELO film-coated tablets and drug substances. The quality by design (QbD) concept was utilized to verify the method performance.
Topics: Drug Stability; Chromatography, High Pressure Liquid; Pyrazoles; Reproducibility of Results
PubMed: 36416121
DOI: 10.1093/jaoacint/qsac153 -
Plastic Surgical Nursing : Official... 2009In this article, you'll learn about six new drugs, including: * clevidipine, an I.V. antihypertensive for use when oral medication isn't feasible * romiplostim and... (Review)
Review
In this article, you'll learn about six new drugs, including: * clevidipine, an I.V. antihypertensive for use when oral medication isn't feasible * romiplostim and eltrombopag olamine, new agents for chronic immune thrombocytopenic purpura * C1 inhibitor (human) for hereditary angioedema. Unless otherwise specified, the information in the following summaries applies to adults, not children. Consult the package insert for information about each drug's safety during pregnancy and breast-feeding. Also consult a pharmacist, the package insert, or a comprehensive drug reference for more details on precautions, drug interactions, and adverse reactions for all these drugs.
Topics: Adrenergic Uptake Inhibitors; Anti-Inflammatory Agents; Antihypertensive Agents; Drug Monitoring; Hematologic Agents; Humans; Immunologic Factors
PubMed: 20029305
DOI: 10.1097/PSN.0b013e3181d0514a -
Molecules (Basel, Switzerland) Dec 2020Eltrombopag, of CHNO chemical formula, is a drug used against thrombocytopenia, marketed worldwide under different tradenames in the form of its bis-olamine salt. The...
Eltrombopag, of CHNO chemical formula, is a drug used against thrombocytopenia, marketed worldwide under different tradenames in the form of its bis-olamine salt. The free acid (CAS no. 496775-61-2) is an intermediate species used for the final drug isolation and is reported to crystallize in more than 20 distinct crystal forms, including a large number of hydrates and solvates. Their identification, and, ultimately, their quantification in industrial lots require the usage of accurately measured X-ray powder diffraction pattern, as well as the assessment of the metrical features (crystal symmetry and lattice parameters), nowadays accessible by powerful crystallographic software. Here, the complete indexing of 13 monophasic samples, prepared using literature or newly tailored crystallization methods, jointly to simultaneous thermogravimetric and calorimetric analyses and to variable temperature X-ray diffraction studies, provide a clear picture of the stability fields of the different crystal phases and their mutual interconversion processes, leading, in a few cases, to new and unexpected crystalline polymorphs or solvates of the pristine unsolvated Form I.
Topics: Benzoates; Crystallization; Crystallography, X-Ray; Humans; Hydrazines; Hydrogen Bonding; Molecular Structure; Powder Diffraction; Pyrazoles; Solvents; Thermogravimetry; Thrombocytopenia; Water; X-Ray Diffraction
PubMed: 33375645
DOI: 10.3390/molecules26010065 -
Methods and Findings in Experimental... Jun 2009(+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole,...
(+)-Dapoxetine hydrochloride; Abatacept, Adalimumab, Agalsidase beta, Alemtuzumab, Alglucosidase alfa, Aliskiren fumarate, Ambrisentan, Amlodipine, Aripiprazole, Atrasentan, Azacitidine, Azelnidipine; Belotecan hydrochloride, Bevacizumab, Bilastine, Biphasic insulin aspart, Bortezomib, Bosentan; Caspofungin acetate, CG-100649, Cinacalcet hydrochloride, Clindamycin phosphate/ benzoyl peroxide; Dasatinib, Denosumab, Duloxetine hydrochloride, Dutasteride, Dutasteride/tamsulosin; Ecogramostim, Eculizumab, Eltrombopag olamine, EndoTAG-1, Erlotinib hydrochloride, Everolimus, Exenatide, Ezetimibe; FAHF-2, Fondaparinux sodium; Gefitinib, Golimumab; HEV-239, HSV-TK; Imatinib mesylate, Indium 111 ((111)In) ibritumomab tiuxetan, Influenza vaccine(surface antigen, inactivated, prepared in cell culture), Insulin glargine; Kisspeptin-54; Lidocaine/prilocaine, Lomitapide; Maraviroc, Mirodenafil hydrochloride, MK-8141, MVA-Ag85A; Nilotinib hydrochloride monohydrate; Olmesartan medoxomil; Paclitaxel-eluting stent, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pitavastatin calcium, Prasugrel; Recombinant human relaxin H2, RHAMM R3 peptide, Rivaroxaban, Rosuvastatin calcium, RRz2; Sagopilone, Salinosporamide A, SB-509, Serlopitant, Sirolimus-eluting stent, Sorafenib, Sunitinib malate; Tadalafil, Temsirolimus, Teriparatide, TG-4010, Tositumomab/iodine (I131) tositumomab; Velusetrag Hydrochloride; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan.
Topics: Clinical Trials as Topic; Humans
PubMed: 19649342
DOI: No ID Found -
Cureus Jun 2022Eltrombopag olamine (ELT) is a synthetic nonpeptide with a low molecular weight that has been investigated in various phase-3 studies and shown to be efficacious at a...
BACKGROUND
Eltrombopag olamine (ELT) is a synthetic nonpeptide with a low molecular weight that has been investigated in various phase-3 studies and shown to be efficacious at a typical dose of 50 mg. Varied ethnic groups have reported different responses to ELT.
AIM
The aim is to examine the efficacy of ELT in Asian and Arab patients with immune thrombocytopenia (ITP) from the Indian subcontinent by starting with (12.5 mg, as a minimum dose) and gradually increasing to a maximum dose of 50 mg.
METHODS
Between January 2015 and January 2019, we reviewed the electronic health records of non-Arab Asian (n = 17) versus Arab (n = 41) patients who were ≥18 years old, residing in Qatar, and with confirmed diagnoses with chronic ITP and under active treatment with a platelet count of 30,000/L, and bleeding symptoms. Following receiving ELT for three months or longer at various dosages, patients' response was examined.
RESULTS
After three months of ELT therapy, the response rate (platelet count of 50,000/L) was equivalent in non-Arab (88.2%) versus Arab (87.5%) patients. However, to achieve an adequate response, 26% of Arab patients required a lower dose of 12.5 or 25 mg, and 41.5% required a higher dose of 50 mg.
CONCLUSION
In adult chronic ITP patients, ELT is typically well-tolerated and delivers the desired outcomes. In 67.5% of Arab patients, smaller dosages of ELT (12.5-50 mg) were helpful in sustaining acceptable PLT levels. This helps patients get the most benefit at the lowest feasible dose, reducing toxicity and expense.
PubMed: 35812564
DOI: 10.7759/cureus.25701 -
Methods and Findings in Experimental... Nov 2010Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from...
Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Trials Knowledge Area of Thomson Reuters Integrity(SM), the drug discovery and development portal, http://www.thomsonreutersintegrity.com. This issue focuses on the following selection of drugs: Abatacept, Adalimumab, AdCD40L, Adefovir, Aleglitazar, Aliskiren fumarate, AM-103, Aminolevulinic acid methyl ester, Amlodipine, Anakinra, Aprepitant, Aripiprazole, Atazanavir sulfate, Axitinib; Belimumab, Bevacizumab, Bimatoprost, Bortezomib, Bupropion/naltrexone; Calcipotriol/betamethasone dipropionate, Certolizumab pegol, Ciclesonide, CYT-997; Darbepoetin alfa, Darunavir, Dasatinib, Desvenlafaxine succinate, Dexmethylphenidate hydrochloride cogramostim; Eltrombopag olamine, Emtricitabine, Escitalopram oxalate, Eslicarbazepine acetate, Eszopiclone, Etravirine, Everolimus-eluting coronary stent, Exenatide, Ezetimibe; Fenretinide, Filibuvir, Fludarabine; Golimumab; Hepatitis B hyperimmunoglobulin, HEV-239, HP-802-247, HPV-16/18 AS04, HPV-6/11/16/18, Human albumin, Human gammaglobulin; Imatinib mesylate, Inotuzumab ozogamicin, Invaplex 50 vaccine; Lapatinib ditosylate, Lenalidomide, Liposomal doxorubicin, Lopinavir, Lumiliximab, LY-686017; Maraviroc, Mecasermin rinfabate; Narlaprevir; Ocrelizumab, Oral insulin, Oritavancin, Oxycodone hydrochloride/naloxone; Paclitaxel-eluting stent, Palonosetron hydrochloride, PAN-811, Paroxetine, Pazopanib hydrochloride, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Pertuzumab, Pitavastatin calcium, Posaconazole, Pregabalin, Prucalopride succinate; Raltegravir potassium, Ranibizumab, RHAMM R3 peptide, Rosuvastatin calcium; Salclobuzic acid sodium salt, SCY-635, Selenate sodium, Semapimod hydrochloride, Silodosin, Siltuximab, Silybin, Sirolimus-eluting stent, SIR-Spheres, Sunitinib malate; Tapentadol hydrochloride, Tenofovir disoproxil fumarate, Tocilizumab, Tositumomab/iodine (I131) tositumomab, Trabectedin, TransVax™ hepatitis C vaccine; Ustekinumab; V-260, Valspodar, Varenicline tartrate, VCL-IPT1, Vildagliptin, VRC-HIVADV014-00-VP, VRC-HIVDNA009-00-VP, VRC-HIVDNA016-00-VP; Yttrium 90 (90Y) ibritumomab tiuxetan, Yttrium Y90 Epratuzumab; Zibotentan, Zotarolimus-eluting stent.
Topics: Clinical Trials as Topic; Humans
PubMed: 21225019
DOI: 10.1358/mf.2010.32.9.1563109 -
Methods and Findings in Experimental... May 2009(-)-Gossypol; Abacavir sulfate/lamivudine, ACAM-1000, ACE-011, Agomelatine, AGS-004, Alemtuzumab, Alvocidib hydrochloride, AMG-317, Amlodipine, Aripiprazole, Atazanavir...
(-)-Gossypol; Abacavir sulfate/lamivudine, ACAM-1000, ACE-011, Agomelatine, AGS-004, Alemtuzumab, Alvocidib hydrochloride, AMG-317, Amlodipine, Aripiprazole, Atazanavir sulfate, Azacitidine; Becatecarin, Belinostat, Bevacizumab, BMS-387032, BMS-690514, Bortezomib; Casopitant mesylate, Cetuximab, Choline fenofibrate, CK-1827452, Clofarabine, Conivaptan hydrochloride; Dabigatran etexilate, DADMe-Immucillin-H, Darbepoetin alfa, Darunavir, Dasatinib, DC-WT1, Decitabine, Deferasirox, Degarelix acetate, Denenicokin, Denosumab, Dienogest, Duloxetine hydrochloride; Ecogramostim, Eculizumab, Edoxaban tosilate, Elacytarabine, Elesclomol, Eltrombopag olamine, Enfuvirtide, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Etravirine; Flibanserin, Fludarabine, Fondaparinux sodium, Fosamprenavir calcium; Gefitinib, Genistein; I-131-L19-SIP, Idrabiotaparinux sodium, Imatinib mesylate, IMGN-901, Ipilimumab; Laromustine, Lenalidomide, Liposomal cisplatin, Liraglutide, Lisdexamfetamine mesilate, Lopinavir, Lopinavir/ritonavir; Maraviroc, MDV-3100, Mecasermin rinfabate, MP-470, Mycophenolic acid sodium salt; Naproxcinod, NB-002, Nesiritide, Nilotinib hydrochloride monohydrate, NK-012; Palonosetron hydrochloride, Panobinostat, Pegfilgrastim, Peginterferon alfa-2a, Pitavastatin calcium, PL-3994, Plerixafor hydrochloride, Plitidepsin, PM-10450; Raltegravir potassium, Recombinant human soluble thrombomodulin, ReoT3D, RHAMM R3 peptide, Rivaroxaban, Romiplostim, Rosuvastatin calcium, Rozrolimupab; Sabarubicin hydrochloride, Salinosporamide A, Sirolimus-eluting stent, Smallpox (Vaccinia) Vaccine, Live, Sorafenib; Tenofovir disoproxil fumarate, Tenofovir disoproxil fumarate/emtricitabine, Teriparatide, Tipifarnib, Tipranavir, Trabectedin, Trifluridine/TPI; Vardenafil hydrochloride hydrate, Vinflunine, Volociximab, Vorinostat; Ximelagatran; Yttrium 90 (90Y) ibritumomab tiuxetan; Ziprasidone hydrochloride, Zoledronic acid monohydrate.
Topics: Clinical Trials as Topic; Humans
PubMed: 19557204
DOI: 10.1358/mf.2009.31.4.1373959