The edition · Clinical Pharmacology
Enzyme-inducing antiseizure drugs left DOAC levels subtherapeutic, and doubling the dose did not fix it
A scoping review of a dangerous combination, a reassuring calcium interaction study in transplant recipients, PPIs that blur CYP2C19 genotype, and a neoplasm signal regulators may have set aside too quickly.
The edition in brief
A scoping review of 30 reports (Therapeutic Drug Monitoring, 23 October) found enzyme-inducing antiseizure medications, chiefly carbamazepine, phenobarbital, primidone and oxcarbazepine, were consistently linked to subtherapeutic DOAC concentrations and serious clinical failures, and doubling the DOAC dose did not prevent events in several cases. Evidence for levetiracetam and valproate was limited and inconsistent. In 25 kidney transplant recipients (British Journal of Clinical Pharmacology, 31 October), calcium with vitamin D taken alongside mycophenolate and tacrolimus did not change total exposure to either drug, suggesting dose separation is unnecessary. In 2818 CYP2C19-genotyped patients on escitalopram (Clinical Pharmacology & Therapeutics, 14 October), proton pump inhibitors blunted the expected genotype difference in metabolism, more with omeprazole or esomeprazole than pantoprazole. A Drug Safety analysis (14 October) argues the dose-related neoplasm imbalance in fezolinetant's phase 3 programme deserves structured surveillance rather than dismissal. The FDA lists a Class II recall of compounded tirzepatide syringes over sterility. The pearl covers calcium and chelation interactions that do matter.
Calcium did not alter tacrolimus or mycophenolate exposure in transplant recipients
In stable kidney transplant recipients, calcium may be co-administered with mycophenolate and tacrolimus without dose separation.
Proton pump inhibitors blurred the CYP2C19 genotype signal for escitalopram
When a patient on escitalopram takes omeprazole or esomeprazole, do not rely on CYP2C19 genotype alone.
A Drug Safety analysis questions the dismissal of fezolinetant's neoplasm signal
Prescribe fezolinetant with informed discussion of an unresolved neoplasm signal, and report new tumours.
FDA lists a Class II recall of compounded tirzepatide syringes
Ask about the source of a patient's incretin injection; compounded syringes have sterility recalls.
The calcium interactions that do need spacing
Space calcium and iron from levothyroxine, quinolones, tetracyclines and bisphosphonates.
Avoid DOACs with enzyme-inducing antiseizure drugs; dose doubling did not work
Do not pair a DOAC with an enzyme-inducing antiseizure drug; switch one of them instead of raising the dose.
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