The edition · Clinical Pharmacology
Tacrolimus after Paxlovid: withhold, then restart at 10% and step up over nine days
A Japanese pharmacokinetic model turns a known interaction into a restart schedule. Also: a structured adverse-effect check for older patients on many drugs, PCSK9 inhibitors in a signal search, CYP2D6 and metoprolol, and a premixed amiodarone recall.
The edition in brief
A population pharmacokinetic analysis of 15 transplant patients in Japan found that nirmatrelvir/ritonavir almost completely blocked tacrolimus clearance and raised its relative bioavailability about eightfold; simulations support withholding tacrolimus during the five-day course and restarting at 10% of the usual dose the day after it ends, then 20% on day 3, 50% on day 6 and full dose on day 9, guided by levels. In a small cluster-randomised trial in Welsh general practice, a patient-completed adverse drug reaction profile for people aged 65 or over on more than four medicines led to more problems being addressed (82% vs 35%). A French nationwide sequence-symmetry analysis of 36,163 PCSK9 inhibitor starters found only two weak signals, both likely confounding. In 996 metoprolol users, higher CYP2D6 metaboliser status was associated with lower mortality (HR 0.82). The FDA lists a Class II recall of Baxter's premixed Nexterone amiodarone bags for manufacturing-practice deviations.
A patient-completed adverse-effect profile surfaced problems that routine review missed
At medication review for older patients on many drugs, use a structured symptom checklist to find adverse effects they have not reported.
PCSK9 inhibitors: a broad signal search found little of concern
A large real-world signal search found no new safety concern with PCSK9 inhibitors.
CYP2D6 metaboliser status was associated with survival in metoprolol users
If a patient has marked bradycardia on standard metoprolol, think of CYP2D6 inhibitors or poor metabolism and consider bisoprolol.
Class II recall: Baxter Nexterone premixed amiodarone 360 mg/200 mL
Check stock for affected Nexterone lots; if you switch to amiodarone ampoules, follow dilution rules and watch for hypotension.
Metformin and B12: the harm that looks like diabetes
Check vitamin B12 in patients on long-term metformin, especially if they develop neuropathy, anaemia or cognitive change.
Tacrolimus and nirmatrelvir/ritonavir: a model-based restart schedule
After nirmatrelvir/ritonavir, restart tacrolimus at about 10% of the usual dose and step up over nine days, guided by trough levels.
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