Gentamicin (Renal Dosing/TDM)

Source: UK SPC (eMC) for Cidomycin 80mg/2ml Solution for Injection, section 4.2 (https://www.medicines.org.uk/emc/product/14742/smpc). A dosing frequency of more than twice daily may be adopted for some specific pathogens or sites of infection as recommended in national and local guidance. ONCE DAILY DOSING IS NOT RECOMMENDED IN CASES OF ENDOCARDITIS, depending on the responsible pathogens — national and local guidance on treatment with gentamicin and serum level monitoring in endocarditis should be followed. URINARY TRACT INFECTION: in patients with normal renal function, 160 mg once daily may be used. GENTAMICIN SHOULD NOT BE PRESCRIBED IF SERUM CONCENTRATIONS CANNOT BE MONITORED. THERAPEUTIC DRUG MONITORING (section 4.2): regular serum concentration monitoring is recommended for all patients, and especially in the elderly, newborns, obesity, impaired renal function and cystic fibrosis. There are no universally accepted guidelines for TDM of gentamicin, and local monitoring and dose adjustment guidelines should be followed where available. PRE-DOSE ('trough') monitoring is recommended to ensure the interval between doses is correct; troughs are measured at the end of a dosing interval and SHOULD NOT EXCEED 1 mg/L for once daily dosing or 2 mg/L for multiple daily dosing — levels in excess of these indicate the need to EXTEND THE INTERVAL between doses, NOT to reduce the dose. POST-DOSE ('peak') monitoring is recommended to check the adequacy of a dose or that it is not excessive; peaks should be measured one hour after an intravenous or intramuscular bolus dose, or 30 minutes after the end of an infusion. A plasma concentration below 4 mg/L indicates the dose is likely to be inadequate and a dose increase should be considered; concentrations above 10 mg/L indicate an increased risk of toxicity, particularly ototoxicity, and a dose reduction should be considered. Any change in dose should be re-assessed with pre- and post-dose levels to confirm the adequacy of the new dose and the appropriateness of the dose interval. SAFETY (section 4.4): ototoxicity (loss of balance and hearing loss, which may be irreversible) and nephrotoxicity are the key risks; important risk factors include renal impairment, high doses, prolonged duration of treatment and age (neonates/infants and possibly the elderly). Monitoring of vestibule, cochlea and renal function is recommended before, during and shortly after treatment. Because risk relates to total exposure, duration of therapy should be the shortest possible compatible with clinical recovery. There is an increased risk of ototoxicity in patients with mitochondrial DNA mutations (particularly the nucleotide 1555 A to G substitution in the 12S rRNA gene) even when serum levels are within range — alternative treatment options should be considered in such patients, and in patients with a maternal history of relevant mutations or aminoglycoside-induced deafness, alternative treatments or genetic testing prior to administration should be considered. In significant obesity, serum concentrations should be closely monitored and a dose reduction considered. Gentamicin should be used with care in conditions characterised by muscular weakness. SOURCE LIMITATION: eMC section 4.5 was NOT captured in this bundle and the openFDA/US label retrieved contains no drug interactions section — NO interactions list is therefore given below and section 4.5 must be checked on the SPC. Sections 4.4 and 4.8 were truncated at the fetch limit.

dosePerKg is left null because the SPC states RANGES by age band, not a single per-kg value, and all values are DAILY totals, not per-dose figures. Section 4.2 verbatim bands: children aged 1 year and above and adolescents with normal renal function — 3 to 6 mg/kg/day as one single dose (preferred) or two divided doses; infants after the first month of life — 4.5 to 7.5 mg/kg/day as one single dose (preferred) or two divided doses; neonates and pre-term infants (aged 0 to 4 weeks old) — 4 to 7 mg/kg/day, given as one single dose because of the longer half-life. Peri-operative prophylaxis and renal adjustment principles for children are not separately tabulated in this SPC; serum level monitoring is specifically recommended in newborns. Verify all paediatric dosing against a children's formulary.