Effect of co-administration of lidocaine on the pain and pharmacokinetics of intramuscular amikacin in children with multidrug-resistant tuberculosis: a randomized crossover trial

BACKGROUND: Currently recommended treatment for multidrug-resistant (MDR) tuberculosis (TB) includes 4-8 months of an injectable medication, which is poorly tolerated. We evaluated the impact of co-administering lidocaine on pain and pharmacokinetics of intramuscular injections of amikacin in children with MDR-TB. METHODS: Children 8-18 years of age, receiving amikacin for MDR-TB treatment in Cape Town, South Africa, were eligible for this randomized crossover trial. Participants received a 15 mg/kg dose of intramuscular amikacin with and without additional lidocaine (0.2-0.4 mg/kg) on different days, and were randomized to the order of the treatments (the sequence). Participants and staff completing evaluations were blinded to sequence. Samples were drawn pre-dose, and at 1, 2, 4, 6 and 8 hours post-dose for measurement of plasma amikacin concentrations. Pain was assessed by participants using the Wong Baker FACES pain scale (0 to 5) pre-dose, immediately after the injection and then at 30 and 60 minutes. Pharmacokinetic measures were calculated using noncompartmental analysis. RESULTS: Twelve children were included, median age 11.5 years (IQR 9.9-13.4y). Participant-reported pain scores immediately after the amikacin injection were lower when lidocaine was co-administered: 1.0 (IQR 0.5-2.0) with lidocaine vs. 2.5 (1.0-4.0) without lidocaine (p=0.004). The median area under the concentration time curve (AUC)0-8 and median maximum plasma concentration (Cmax) of amikacin were 109.0 μg*h/mL (IQR 84.7-121.3) and 36.7 μg/mL (IQR 34.1-40.5) with lidocaine compared to 103.3 μg*h/mL (IQR 81.7-135.0; p=0.814) and 34.1 μg/mL (IQR 35.6-46.4; p=0.638) without lidocaine, respectively. CONCLUSIONS: The co-administration of lidocaine resulted in reduced pain immediately after the injection and did not alter amikacin AUC or Cmax