Sofosbuvir/Ribavirin therapy for patients experiencing failure of ombitasvir/paritaprevir/ritonavir + ribavirin therapy: Two cases report and review of literature

BACKGROUND The effectiveness of sofosbuvir/ribavirin(SOF/RBV) combination therapy,which is one of the 1 st-choice therapeutic options for patients with hepatitis C virus(HCV) genotype 2(HCV-G2) in Japan according to the most recent version of the Japan Society of Hepatology guideline, for patients who experienced failure of the ombitasvir/paritaprevir/ritonavir plus ribavirin(OBV/PTV/r+RBV) combination therapy, which was another option for patients with HCV-G2, is unknown.CASE SUMMARY We evaluated the effects of SOF/RBV combination therapy in two patients with genotype 2 a who could not achieve a sustained virological response(SVR) by OBV/PTV/r+RBV combination therapy. One patient was complicated with VogtKoyanagi-Harada(VKH) disease. Resistance-associated variations before SOF/RBV combination therapy were not detected in two patients. Both patients had an SVR at 12 wk after the treatment(SVR12). Regarding adverse events(AEs), itching, chill, a dull feeling in the throat and cough as well as increase of alanine transaminase level were shown in one patient, while a headache and deterioration of light aversion probably due to the recurrence of VKH disease were shown in the other patients. In addition, the latter patient developed arthralgia and morning stiffness approximately 7 wk after the therapy and turned out to be diagnosed with rheumatoid arthralgia.CONCLUSION SOF/RBV therapy might be effective for patients experiencing failure of OBV/PTV/r+RBV therapy, but caution should be taken regarding the AEs.

Control strategy and methods for continuous direct compression processes

We presented a control strategy for tablet manufacturing processes based on continuous direct compression.The work was conducted by the experts of pharmaceutical companies,machine suppliers,academia,and regulatory authority in Japan.Among different items in the process,the component ratio and blended powder content were selected as the items requiring the control method specific to continuous manufacturing different from the conventional batch manufacturing.The control and management of the Loss in Weight(LIW)feeder were deemed the most important,and the Residence Time Distribution(RTD)model were regarded effective for setting the control range and for controlling of the LIW feeder.Based on these ideas,the concept of process control using RTD was summarized.