Abstract
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 coadministering 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 predose, and at 1, 2, 4, 6 and 8 hours postdose for measurement of plasma amikacin concentrations. Pain was assessed by participants using the Wong Baker FACES pain scale (0-5) predose, 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 (interquartile range [IQR], 9.9-13.4 years). Participant-reported pain scores immediately after the amikacin injection were lower when lidocaine was coadministered: 1.0 (IQR, 0.5-2.0) with lidocaine versus 2.5 (1.0-4.0) without lidocaine (P = 0.004). The median area under the concentration time curve0-8 and median maximum plasma concentration 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 with 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 coadministration of lidocaine resulted in reduced pain immediately after the injection and did not alter amikacin area under the concentration time curve or maximum plasma concentration.