The ranitidine cancer signal faded once reporting bias was handled; opioid interaction risk in sickle cell disease; lower tacrolimus start after living-donor liver transplant

The edition in brief

A Drug Safety analysis of ranitidine and cancer in the FDA and Japanese adverse-event databases found a surge of 140,985 FAERS cancer reports in 2020 to 2021, mostly consumer-submitted and clustered where regulatory alerts and litigation were active. Signals in unrestricted analyses weakened or disappeared when famotidine was used as an active comparator and when reports were restricted by time; in the Japanese database a signal (PRR 3.54) vanished (0.92) when all involvement types were included. Most large cohort studies showed no increased cancer risk. In a claims analysis of the 100 most prescribed drugs for people with sickle cell disease in the US, 43 carried drug-interaction risk, CYP3A4 accounted for most interactions, and oxycodone (40%) and fentanyl (18.5%), both CYP3A4 substrates, were widely prescribed. A population pharmacokinetic model in 121 adults on dolutegravir 50 mg daily estimated cerebrospinal fluid penetration of 0.15% relative to plasma, with exposure falling as BMI rose (r = -0.34). The FDA database lists a supplement to tirzepatide (Mounjaro) without describing its content. A critical review of 16 pharmacokinetic studies suggests a 30% to 50% lower initial tacrolimus dose after living-donor than deceased-donor liver transplantation, with mycophenolate unchanged. The pearl covers tacrolimus trough sampling.