Pharmaceutical Business Review International’s Post

Drug-induced liver injury (DILI) is a significant clinical concern, with a wide spectrum of presentations ranging from asymptomatic elevation of liver enzymes to severe acute liver failure. The diagnosis of DILI can be challenging due to its variable clinical manifestations and the need to exclude other potential causes of liver injury. This review provides an overview of the pathogenesis, clinical features, diagnostic approach, and management of DILI. The pathogenesis of DILI involves a complex interplay between host factors, drug properties, and immune responses, leading to hepatocellular injury, cholestasis, or a mixed pattern of liver injury. Clinical presentation can vary widely, from mild gastrointestinal symptoms to jaundice, hepatic encephalopathy, and coagulopathy in severe cases. Diagnosis relies on a combination of clinical evaluation, laboratory tests, imaging studies, and occasionally liver biopsy. Prompt identification and discontinuation of the offending drug are essential to prevent further liver damage. Supportive care, including hydration, nutrition, and management of complications, is paramount in managing DILI. Specific therapies such as corticosteroids or N-acetylcysteine may be considered in selected cases. Liver transplantation may be necessary in rare instances of fulminant liver failure. Long-term follow-up is crucial to monitor for chronic liver damage and prevent recurrence upon re-exposure to the offending drug. Patient education regarding medication safety and early recognition of symptoms is essential in preventing DILI. Overall, the management of DILI requires a multidisciplinary approach and individualized treatment plans tailored to the severity and underlying cause of liver injury. If you'd like to get more actual knowledge, please follow me and subscribe to my YouTube channel Drug safety from Galyna Cordero https://lnkd.in/dFbjtrf3 #pharmacovigilance #drug_safety #drugsafety #patientsafety #DILI

Thrilled to share a significant achievement in my academic journey: the first portion of my thesis project has been published! 📝🎉. This publication reflects the dedication, extensive research and analysis along with the invaluable support and guidance from my mentors and supervisor. This publication is just the beginning of sharing insights into the impact of #AugmentedRenalClearance on numerous antimicrobial drugs in the ICU, including #vancomycin. Excited for what lies ahead! #puplishedResearch #pharmacology

DID YOU KNOW THAT DAPRODUSTAT is the only oral HIF-PHI approved by US FDA for treatment of ANAEMIA of CHRONIC KIDNEY DISEASE (CKD) in adults on dialysis. DAPRODUSTAT is the first innovative medicine for treatment of anaemia of CKD in over 30 years and is the only oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI) approved by US FDA, for the once-a-day treatment of anaemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least four months. Daprodustat has not been approved for use in patients who are not on dialysis because its safety has not been established in that population. The FDA approval is based on results from the ASCEND-D trial. Daprodustat (Jesduvroq) is a tablet available in 5 dosage strengths: 1mg, 2mg, 4mg, 6mg, 8mg administered orally once daily, with or without food. Results showed Daprodustat improved or maintained Hb within target levels (10 -11.5 g/dL) for these patients similar to that with patients on recombinant human Erythropoietin and the primary safety analysis of the ITT ( Intention To Treat) population showed that Daprodustat achieved non-inferiority of Major Adverse Cardiovascular Events ( MACE) compared to Erythropoiesis-Stimulating Agents (ESA) control. Over 700 million patients suffer from CKD worldwide, and an estimated 1-in-7 of these patients have anaemia. Mechanism of Action:- Daprodustat increases endogenous erythropoietin in a dose-dependent manner in 6 to 8 hours after administration. With repeated doses, the peak increase in reticulocyte count occurs in 7 to 15 days, with subsequent increases in red blood cell production. New hemoglobin steady-state levels are reached in several weeks after initial administration (∼4 weeks in patients using erythropoiesis-stimulating agents [ESAs] and ∼16 to 20 weeks in patients not using ESAs). The most common side effects of Daprodustat have included high blood pressure, blood clots, abdominal pain, dizziness, and allergic reactions. Daprodustat should not be prescribed to patients with uncontrolled high blood pressure. Hemoglobin levels should be monitored and the Daprodustat dose should be adjusted in patients in whom treatment with cytochrome P-450 [CYP-2C8] inducers (Rifampicin) or Inhibitors ( Gemfibrozil, Clopidogrel etc.) is being initiated or discontinued during Daprodustat treatment unless the starting dose is ≤1 mg. A BIG RELIEF :- A new oral treatment and convenient option for patients of CKD on dialysis, instead of Inj Erythropoietin.

🔬💉 Exciting News in Gastroenterology! Takeda's ENTYVIO SC has received FDA approval for the treatment of adults with moderately to severely active Crohn's disease. This approval is based on the robust findings from the Phase III VISIBLE 2 Study. ENTYVIO SC provides a significant advancement in the management of Crohn's disease, offering patients the convenience and flexibility of at-home administration. This allows for greater control over their treatment schedules and enhances their quality of life. At Synergy Healthcare, we celebrate this milestone in medical science and applaud the efforts of all the collaborators involved in the development and testing of this innovative treatment. As a leader in clinical trials for metabolic and neurological diseases, we remain committed to advancing healthcare and improving patient outcomes. #SynergyHealthcare #ClinicalResearch #CrohnsDisease #ENTYVIO #FDAApproval #Takeda #MedicalInnovation #Healthcare #Pharmaceuticals #Biotech #Neurology #MetabolicDiseases #ClinicalTrials https://lnkd.in/eA6uAzHB

DID YOU KNOW THAT DAPRODUSTAT is the only oral HIF-PHI approved by US FDA for treatment of ANAEMIA of CHRONIC KIDNEY DISEASE (CKD) in adults on dialysis. DAPRODUSTAT is the first innovative medicine for treatment of anaemia of CKD in over 30 years and is the only oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI) approved by US FDA, for the once-a-day treatment of anaemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least four months. Daprodustat has not been approved for use in patients who are not on dialysis because its safety has not been established in that population. The FDA approval is based on results from the ASCEND-D trial. Daprodustat (Jesduvroq) is a tablet available in 5 dosage strengths: 1mg, 2mg, 4mg, 6mg, 8mg administered orally once daily, with or without food. Results showed Daprodustat improved or maintained Hb within target levels (10 -11.5 g/dL) for these patients similar to that with patients on recombinant human Erythropoietin and the primary safety analysis of the ITT ( Intention To Treat) population showed that Daprodustat achieved non-inferiority of Major Adverse Cardiovascular Events ( MACE) compared to Erythropoiesis-Stimulating Agents (ESA) control. Over 700 million patients suffer from CKD worldwide, and an estimated 1-in-7 of these patients have anaemia. Mechanism of Action:- Daprodustat increases endogenous erythropoietin in a dose-dependent manner in 6 to 8 hours after administration. With repeated doses, the peak increase in reticulocyte count occurs in 7 to 15 days, with subsequent increases in red blood cell production. New hemoglobin steady-state levels are reached in several weeks after initial administration (∼4 weeks in patients using erythropoiesis-stimulating agents [ESAs] and ∼16 to 20 weeks in patients not using ESAs). The most common side effects of Daprodustat have included high blood pressure, blood clots, abdominal pain, dizziness, and allergic reactions. Daprodustat should not be prescribed to patients with uncontrolled high blood pressure. Hemoglobin levels should be monitored and the Daprodustat dose should be adjusted in patients in whom treatment with cytochrome P-450 [CYP-2C8] inducers (Rifampicin) or Inhibitors ( Gemfibrozil, Clopidogrel etc.) is being initiated or discontinued during Daprodustat treatment unless the starting dose is ≤1 mg. A BIG RELIEF :- A new oral treatment and convenient option for patients of CKD on dialysis, instead of Inj Erythropoietin.

𝗡𝗼𝘃𝗲𝗹 𝗣𝗮𝘁𝗶𝗲𝗻𝘁-𝗙𝗿𝗶𝗲𝗻𝗱𝗹𝘆 𝗢𝗿𝗼𝗱𝗶𝘀𝗽𝗲𝗿𝘀𝗶𝗯𝗹𝗲 𝗙𝗼𝗿𝗺𝘂𝗹𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝗜𝘃𝗲𝗿𝗺𝗲𝗰𝘁𝗶𝗻 Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient-friendly orodispersible tablet formulation designed for pediatric use (CHILD-IVITAB) has been developed and is entering early phase clinical trials. To inform the pediatric program of CHILD-IVITAB, 16 healthy adults were enrolled in a phase I, single-center, open-label, randomized, 2-period, crossover, single-dose trial which aimed to compare palatability, tolerability, and bioavailability and pharmacokinetics of CHILD-IVITAB and their variability against the marketed ivermectin tablets (STROMECTOL) at a single dose of 12 mg in a fasting state. Palatability with CHILD-IVITAB was considerably enhanced as compared to STROMECTOL. Both ivermectin formulations were well tolerated and safe. Relative bioavailability of CHILD-IVITAB compared to STROMECTOL was estimated as the ratios of geometric means for Cmax,AUC 0-∞, and AUC0-last, which were 1.52 [90% CI: 1.13-2.04], 1.27 [0.99-1.62], and 1.29 [1.00-1.66], respectively. Maximum drug concentrations occurred earlier with the CHILD-IVITAB formulation, with a median Tmax at 3.0 h [range 2.0-4.0 h] versus 4.0 h [range 2.0-5.0 h] with STROMECTOL (P = .004).With CHILD-IVITAB, variability in exposure was cut in half (coefficient of variation: 37% vs 70%) compared to STROMECTOL. Consistent with a more controlled absorption process, CHILD-IVITAB was associated with reduced variability in drug exposure as compared to STROMECTOL. Together with a favorable palatability and tolerability profile, these findings motivate for further clinical studies to evaluate benefits of such a patient-friendly ODT formulation in pediatric patients with a parasitic disease, including infants and young children <15 kg. Learn more here: https://lnkd.in/eB6E9Cxp Paper by: Kim Dao MD, Michael Buettcher MD, Klervi Golhen, PharmD, Jonas Kost MSc, Andreas Schittny PhD, Urs Duthaler PhD, Andy Atkinson PhD, David Haefliger MD, Monia Guidi PhD, Carine Bardinet MSc, Haithem Chtioui MD, Abdelwahab Boulekbache MD, Thierry Buclin MD, Jörg Huwyler PhD, Marc Pfister M.D., Laura E.Rothuizen MD #excipients #odt #drugdelivery #pharmaceuticals

#FDA approved #AbbVie's #Skyrizi (risankizumab-rzaa) to treat adults with moderately to severely active ulcerative colitis (#UC). This approval expands Skyrizi's reach to an additional 1 million US patients and makes it the first IL-23 inhibitor approved for both UC and Crohn disease. Skyrizi is now approved for four indications across immune-mediated inflammatory diseases: plaque psoriasis, psoriatic arthritis, ulcerative colitis and Crohn disease. Skyrizi's sales were $7.7 billion last year, and analysts predict it will peak at $19.7 billion by 2030, significantly bolstering AbbVie's revenues as #Humira faces biosimilar competition. Detailed news here: https://lnkd.in/eBTsm76N Stay updated on the latest trends and news in the pharmaceutical industry. Follow #RASLSS: https://lnkd.in/de5zNWmK #PharmaNews #FDAApproval #Skyrizi #UlcerativeColitis #CrohnsDisease #IL23Inhibitor #MedicalInnovation #Healthcare #Biotech #AbbVie #Immunology #PatientCare #Gastroenterology #Biopharma

The US Food and Drug Administration (FDA) has approved Mirum Pharmaceuticals’ Livmarli (maralixibat) oral solution to treat cholestatic pruritus in patients aged five years and older with progressive familial intrahepatic cholestasis (PFIC). Estimated to affect one in every 50,000 to 100,000 births in the US and Europe, PFIC is a rare genetic disorder that causes progressive liver disease, typically leading to liver failure. Signs and symptoms of the condition usually begin in infancy and include severe pruritus (itching), jaundice and a failure to grow at the expected rate. The FDA’s decision on the therapy covers a broad range of PFIC subtypes and is supported by positive results from the late-stage MARCH study, which included 93 patients across a range of genetic PFIC forms as well as unidentified mutational status. Results showed a “highly statistically significant” reduction in pruritus severity for those receiving Livmarli compared with placebo, Mirum outlined. Chris Peetz, Mirum’s chief executive officer, said Livmarli “has the potential to have a transformational impact for patients with cholestatic pruritus associated with PFIC” and “offers an option for those patients with the rarest of subtypes”. The company has also submitted a supplemental new drug application that supports the use of a higher concentration formulation of Livmarli, potentially enabling a label expansion for younger PFIC patients. Richard Thompson of King’s College London, and an investigator in the MARCH study, said: “Livmarli’s approval in cholestatic pruritus for patients with PFIC is a result of years of investigation and a collection of a strong body of clinical evidence showing meaningful improvements across a number of important parameters, including pruritus, affecting children with PFIC.” Livmarli is already approved in the US to treat cholestatic pruritus in patients aged three months and older with Alagille syndrome, a rare genetic disorder that can affect multiple organ systems of the body, including the liver and heart. Read more: https://lnkd.in/euM2YYQX Stay in touch with all the leading stories, events and opportunities by subscribing to our LinkedIn Newsletter: https://bit.ly/3RbdKtc or joining some of the largest groups most relevant to you: https://bit.ly/4caKquL (A-Z list)

DID YOU KNOW THAT DAPRODUSTAT is the only oral HIF-PHI approved by US FDA for treatment of ANAEMIA of CHRONIC KIDNEY DISEASE (CKD) in adults on dialysis. DAPRODUSTAT is the first innovative medicine for treatment of anaemia of CKD in over 30 years and is the only oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor (HIF-PHI) approved by US FDA, for the once-a-day treatment of anaemia due to chronic kidney disease (CKD) in adults who have been receiving dialysis for at least four months. Daprodustat has not been approved for use in patients who are not on dialysis because its safety has not been established in that population. The FDA approval is based on results from the ASCEND-D trial. Daprodustat (Jesduvroq) is a tablet available in 5 dosage strengths: 1mg, 2mg, 4mg, 6mg, 8mg administered orally once daily, with or without food. Results showed Daprodustat improved or maintained Hb within target levels (10 -11.5 g/dL) for these patients similar to that with patients on recombinant human Erythropoietin and the primary safety analysis of the ITT ( Intention To Treat) population showed that Daprodustat achieved non-inferiority of Major Adverse Cardiovascular Events ( MACE) compared to Erythropoiesis-Stimulating Agents (ESA) control. Over 700 million patients suffer from CKD worldwide, and an estimated 1-in-7 of these patients have anaemia. Mechanism of Action:- Daprodustat increases endogenous erythropoietin in a dose-dependent manner in 6 to 8 hours after administration. With repeated doses, the peak increase in reticulocyte count occurs in 7 to 15 days, with subsequent increases in red blood cell production. New hemoglobin steady-state levels are reached in several weeks after initial administration (∼4 weeks in patients using erythropoiesis-stimulating agents [ESAs] and ∼16 to 20 weeks in patients not using ESAs). The most common side effects of Daprodustat have included high blood pressure, blood clots, abdominal pain, dizziness, and allergic reactions. Daprodustat should not be prescribed to patients with uncontrolled high blood pressure. Hemoglobin levels should be monitored and the Daprodustat dose should be adjusted in patients in whom treatment with cytochrome P-450 [CYP-2C8] inducers (Rifampicin) or Inhibitors ( Gemfibrozil, Clopidogrel etc.) is being initiated or discontinued during Daprodustat treatment unless the starting dose is ≤1 mg. A BIG RELIEF :- A new oral treatment and convenient option for patients of CKD on dialysis, instead of Inj Erythropoietin.

Hello Premera Blue Cross and Chad Murphy, BS, PharmD and Jeff Roe you denied an essential lab test that I ordered for a small child with Crohn's disease. The lab test is to check for drug levels and antibody titers to adalimumab. You stuck the parents with a $560 bill because you deem the test "experimental". My appeal was denied as well, and I have not been granted a peer to peer with one of your medical directors. Please help me understand how you can approve a potent immune suppressing drug in a child and then deny me the ability to check the concentration of this drug? What if I am overdosing her? What if she has high antibody titers and is at risk for anaphylaxis? What if I am under-dosing her and she is at risk of a flare? Do these important questions sound experimental to you? Your policies on "experimental uses" of lab tests in pediatric IBD are outdated and potentially harmful. There are MOUNTAINS of data to support both pro-active and reactive therapeutic drug monitoring in IBD, so your denial on experimental grounds is way out of line. Your argument is years outdated. It's time for a refresh. I am happy to send you a full list of studies to support that TDM is actually standard of care in managing IBD. Many of these were sponsored and supported by Crohn's & Colitis Foundation, American Gastroenterological Association (AGA), American College of Gastroenterology, and North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), and Prometheus Laboratories Inc. who have worked tirelessly to collect the data that supports pro-active and reactive TDM. I have been using adalimumab drug levels for years, and only Premera Blue Cross is denying this test in 2024. Please explain yourself! How are you such an outlier in all of this? And how can you stick a $560 bill to a parent when an expert like myself has deemed this test essential and has then gone to bat with a scientifically sound appeal? I'm disgusted. The family is in tears. My nurses (who spent 6 hours on this appeal) are dejected.