The edition · Clinical Pharmacology
One variant in 330 and a single aminoglycoside dose: the case for MT-RNR1 testing
A UK pharmacogenomics guideline sets out when to test for the mitochondrial variants behind aminoglycoside deafness, and when not to wait. In critically ill children, four in ten posaconazole levels were below target.
The edition in brief
A UK pharmacogenomics guideline, published in July in the British Journal of Clinical Pharmacology, recommends avoiding aminoglycosides in anyone carrying the MT-RNR1 variants m.1555A>G, m.1494C>T or m.1095T>C, present in about 1 in 330 people, which can cause permanent deafness after a single dose; testing should be pre-emptive where aminoglycoside use is predictable, but treatment must not be delayed in an emergency while waiting for a result. A 15-year review of posaconazole levels in a paediatric intensive care unit found 39% below target, strongly associated with the liquid formulation (OR 29.6) but still 28% on intravenous dosing, supporting routine therapeutic drug monitoring. In healthy volunteers, clarithromycin raised exposure to the PDE5 inhibitor aildenafil 2.6-fold while rifampicin cut it by about 99%, a reminder of how completely a strong inducer can erase a CYP3A4 substrate. The FDA lists a Class II recall, dated 9 September, of Baxter's premixed vancomycin 1 g in 200 mL Galaxy containers for manufacturing-practice deviations. The pearl covers the time course of rifampicin induction.
Four in ten posaconazole levels in critically ill children were below target
Measure posaconazole levels in critically ill children and move off the suspension where possible.
FDA Class II recall: premixed vancomycin 1 g Galaxy bags
Check premixed vancomycin stock against the recall and substitute without changing the dosing plan.
Rifampicin cut exposure to a CYP3A4-cleared PDE5 inhibitor by about 99%
Review all CYP3A4 substrates when rifampicin starts; a strong inducer can erase their effect.
Rifampicin induction takes days to build and weeks to fade
Plan monitoring of interacting drugs for two weeks after starting and after stopping rifampicin.
MT-RNR1 testing: avoid aminoglycosides in carriers, but never delay emergency treatment
Test for MT-RNR1 where aminoglycoside use is planned and avoid the class in carriers; do not delay urgent treatment for a result.
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