The edition · Clinical Pharmacology
The ranitidine cancer signal largely disappeared once reporting bias was handled
What active comparators did to the ranitidine signal, an FcRn blocker that lowered autoantibodies without helping pemphigus, ten years of drug-level alerts in a psychiatric hospital, and an FDA supplement for tirzepatide.
The edition in brief
A Drug Safety analysis of the US and Japanese spontaneous reporting databases found a surge of more than 140,000 ranitidine cancer reports in 2020–21, mostly from consumers in regions affected by regulatory action and litigation. Strong signals in crude analyses weakened or vanished when ranitidine was compared with famotidine and when reports were restricted to the period before the recall; in Japan, a reporting ratio of 3.54 fell to 0.92. Most large cohort studies in a systematic review showed no increased cancer risk. In the phase 3 ADDRESS trial, 222 adults with moderate-to-severe pemphigus on prednisone received subcutaneous efgartigimod or placebo; IgG and anti-desmoglein antibodies fell quickly, but complete remission on minimal prednisone at 30 weeks was no more frequent (35.5% vs 30.3%), and steroid use was similar. A ten-year review of 3,700 critical and drug-level alerts at a Chinese psychiatric hospital found drug-concentration alerts made up half, with venlafaxine prominent, alongside leukopenia, low potassium and high glucose, and a third of alerts came from geriatric psychiatry. The FDA recorded a supplement to the tirzepatide new drug application; the database does not state its content.
Efgartigimod cut pemphigus autoantibodies but not disease activity
Lowering pemphigus autoantibodies with efgartigimod did not improve remission over steroids alone; it has no place in pemphigus on this evidence.
Drug-level alerts made up half of critical results in a psychiatric hospital
In psychiatric patients, especially the elderly, drug-level alerts and leukopenia, potassium and glucose problems are where monitoring pays off.
FDA supplement recorded on the tirzepatide new drug application
An FDA supplement has been recorded for tirzepatide; its content is not yet stated, so prescribing is unchanged for now.
Time the drug level before you interpret it
A drug level is only interpretable if you know when it was drawn relative to the last dose.
Ranitidine's cancer signal largely reflected reporting bias, not carcinogenicity
Past ranitidine use does not need cancer screening; the spontaneous-report signal largely reflected publicity-driven reporting.
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