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.
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.
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.
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.
From the *Department of Paediatrics and Child Health, Desmond Tutu TB Centre, Faculty of Medicine and Health Sciences, Stellenbosch University, South Africa
†Department of Paediatrics, Imperial College London, London, United Kingdom
‡Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Accepted for publication October 31, 2017.
Supported by The Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award number R01HD069169 (ACH, HSS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ACH receives funding from the South Africa National Research Foundation (NRF) (SaRCHI Chair). HSS receives funding from the South Africa NRF. HMM is funded by the Wellcome Trust (206379/Z/17/Z) and receives funding from the South Africa NRF (grant 90729. This study also received funding support from the Harry Crossley Foundation (PCR). The University of Cape Town Clinical Pharmacology laboratory is supported in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (UM1 AI068634, UM1 AI068636 and UM1AI106701, U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health (AI068632).
The authors have no funding or conflicts of interest to disclose.
Drs. Hesseling and Schaaf contributed equally to this work.
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Address for correspondence: Anthony J. Garcia-Prats, MD, Desmond Tutu TB Centre, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town, 8000, South Africa. E-mail: firstname.lastname@example.org.