Ponatinib: a miracle or a disaster in chronic myeloid leukemia

Chronic myeloid leukemia (CML), the most common myeloproliferative disorder, occurring due to balanced reciprocal translocation between chromosome 9 and 22 and resulting in a chimeric oncogene called breakpoint cluster region-abelson (BCR-ABL) whose protein product has tyrosine kinase activity, causes uncontrolled proliferation of the myeloid cells. Although, imatinib, the first-generation tyrosine kinase inhibitor (TKI) achieved an extremely high response rate, some patients developed resistance to it. Thus, second-generation TKIs such as nilotinib, dasatinib, bosutinib were developed which proved very useful, till the emergence of T315I point mutation which occurs in the BCR-ABL gene and renders CML resistant to previous TKIs. Ponatinib, a third generation TKI approved by the United States Food and Drug Administration (FDA), showed great promise as it was effective even against T315I point mutation. However, a recent increase in the incidence of blood clots observed in patients taking ponatinib has resulted in FDA temporarily suspending all trials, marketing and distribution of the drug. Hence, whether ponatinib evolves as a miracle or disaster for the patients of CML is yet to be answered

A study on adverse drug reactions to non-ionic contrast medium in an Indian population: a 1-year experience

Background: To the best of our understanding, very few studies focusing on the adverse drug reaction (ADR) profile of non-ionic contrast medium (NICM) has been carried out until date among the Indian population. Hence, this study was planned. We sincerely believe that the knowledge gathered from this study can improve safer usage of these agents among the patients of Indian origin. The objective was to evaluate the incidence and severity of ADRs of non-ionic radio contrast media (CM) used in tertiary care hospital in Eastern India.Methods: For the duration of 1-year from July 2011 to July 2012, we prospectively recorded all the ADRs associated with the administration of NICM (iohexol and ioversol) in 3708 patients of Indian origin undergoing computed tomography scan at the hospital. The average median age, weight, dose used; types of ADRs, concomitant medication, final diagnosis, reasons for use were recorded and analyzed with appropriate statistical tools. Causality assessment was performed using Naranjo scale.Results: Eleven of 3708 patients who received either ioversol or iohexol developed ADRs (i.e. 0.3% of patients). The most common ADR was rigor. The incidences of mild, moderate and severe reactions were 55%, 36% and 9%, respectively. Average median age, weight, and dose used were 35 years, 66 kg and 70 ml, respectively. All the ADRs were early (occurred within 1 hr of CM administration). Due to logical constraints, the follow-up of these patients was not possible and hence late ADRs were not captured. The common concomitant medication used was pantoprazole (63.63% of patients). The difference in the incidence of ADRs by age distribution (Group 1 - Iohexol, Group 2 - Ioversol) and weight distribution was not statistically significant (p=0.75 and p=0.18, respectively). Causality analysis revealed that all the ADRs were possible (Score of 4). Interestingly, the incidence of reactions was noted to be higher in patients with a history of gastro intestinal disorders (45.45%).Conclusions: This pilot study reveals that adverse reactions to NICM are rare and severe reactions are less common among the patients of Indian origin. However, a larger multicentric study across the country should be carried out to understand the safety profile of these CM better among the Indian population

Study of Clinicodemographic Profile of Adverse Cutaneous Drug Reactions in Indian Perspective

Background: Cutaneous adverse drug reactions are an important group of disorders which pose considerable amount of diagnostic and therapeutic challenges. The incidence of CADRs is estimated to be 1–2% in the general population. Newer insights have been developing in the field of factors affecting CADRs and the need for studies in the Indian population regarding the newer trends in cutaneous adverse effects. Materials and Methods: A prospective and observational study was conducted in the Department of Pharmacology and Collaboration with Department of Dermatology in MGM Medical College and LSK Hospital. All cases of suspected CADRs in patients with systemically administered drugs were actively screen by a senior dermatologist. Causality assessment was done by a Pharmacologist using WHO UMC scale. Only those cases where the causality was certain probable/likely were recorded. Results: This sampling comprised of 77 CADRs over a period of 1 year from June 2012 to May 2013. The clinical pattern and spectrum of CADRs were studied in 77 subjects. A wide clinical spectrum of CADRs ranging fixed drug eruptions to serious Stevens Johnson syndrome (SJS) was observed. The predominant pattern of reactions observed was fixed drug eruptions FDE (35.1%) followed by acneiform eruptions (23.4%), erythema multiforme (9.1%), and phototoxic drug reactions (7.8%). The antimicrobials causing FDE were macrolides, cephalosporins, and fluoroquinolones. Among the NSAIDs causing FDE, most were due to diclofenac (70%). CADRs were seen most commonly in the 31–40 (26%) years age group followed by 11–20 (24.7%) years and 41–50 (19.5%) years with mean age 32.09 years. Only 5.2% patients were more than 60 years, oldest being 67 years. Antimicrobials were the most common drug group incriminated in 34% patients followed by NSAIDs in 29% cases and steroids in 25% cases. Among NSAIDs, maximum number of CADRs were caused by ibuprofen (40.9%) followed by diclofenac (36.4%), paracetamol (9%), aceclofenac (9%), and nimesulide (4.5%). Serious reactions were infrequent. Conclusion: Most of the reactions were mild (53%) to moderate (42%) requiring no major medical intervention. However, a larger and multi-centric study needs to be conducted across the state to obtain more information about CADRs among the state population