Reaksi Obat yang Tidak Diharapkan dari Penggunaan Teofilin akibat Interaksi dengan Obat Penghambat Enzim Sitokrom P450 1A2: Laporan Kasus
Abstract
Teofilin merupakan bronkodilator dengan rentang konsentrasi terapetik sempit dan memiliki variabilitas antarindividu secara farmakokinetik. Klirens teofilin dipengaruhi oleh usia, fungsi hati, dan interaksi obat. Kami laporkan sebuah kasus anak usia 2 tahun 8 bulan dengan sepsis disertai gangguan fungsi ginjal dan hati, mengalami reaksi obat yang tidak diharapkan yang diduga efek toksisitas teofilin akibat interaksi obat, yaitu tremor, kejang, gelisah, dan takikardia. Dilakukan pengecekan interaksi obat dengan menggunakan Micromedex® dan penilaian hubungan kausalitas menggunakan Drug Interaction Probability Scale (DIPS). Dari penilaian DIPS, paling mungkin disebabkan oleh interaksi obat teofilin dan siprofloksasin, didukung dengan tanda dan gejala toksisitas hilang setelah teofilin dihentikan. Efek tersebut terjadi karena peningkatan dosis teofilin yang tidak diikuti dengan peningkatan klirens teofilin pada anak. Penyesuaian dosis dan pemantauan kadar teofilin dalam darah diperlukan untuk mencegah efek toksisitas.
Kata kunci: Interaksi obat, siprofloksasin, teofilin, toksisitas obat
Adverse Drug Reaction due to the Drug Interaction between Theophylline and a CYP1A2 Drug Inhibitor: Case Report
Abstract
Theophylline is a bronchodilator with narrow therapeutic concentration, as well as inter-individual pharmacokinetic variability, and the clearance of this drug is influenced by age, liver function, and drug interactions. This study, therefore, reports the case of a 32 month-old child diagnosed with sepsis as well as renal and liver impairment and exhibiting theophylline toxicity symptoms of tremor, seizure, agitation, as well as tachycardia. The drug interaction and causality relationship were assayed using Micromedex® and a Drug Interaction Probability Scale (DIPS), respectively. Based on the DIPS, the most probable cause is the drug interaction of theophylline and ciprofloxacin. Furthermore, all the symptoms disappeared after theophylline was continued. Also, an increase in the theophylline dose did not lead to an increase in the drug’s clearance, therefore, to prevent toxicity, the dosage ought to be adjusted and the drug concentration must be monitored.
Keywords: Ciprofloxacin, drug interaction, drug toxicity, theophylline
Keywords
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Palleria C, Paolo AD, Giofrè C, Caglioti C, Leuzzi G, Siniscalchi A, et al. Pharmacokinetic drug-drug interaction and their implication in clinical management. J Res Med Sci. 2013;18(7):601–10.
Barnes PJ. Theophylline. Am J Respir Crit Care Med. 2013;188(8):901–6. doi: 10.1164/rccm.201302-0388PP
PHARMGKB. Theophylline pathway, pharmacokinetic [diunduh 1 September 2020]. Tersedia dari: https://www.pharm gkb.org/pathway/PA165958541
Antoniou T, Gomes T, Mamdani MM, Juurlink DN. Ciprofloxacin-induced theophylline toxicity: A population-based study. Eur J Clin Pharmacol. 2011;67(5):521–6. doi: 10.1007/s00228-010-0985-0
Ma YJ, Jiang DQ, Meng JX, Li MX, Zhao HH, Wang Y,et al. Theophylline: A review of population pharmacokinetic analyses. J Clin Pharm Ther. 2016;41(6):594–601. doi: 10.1111/jcpt.12435
Theophylline. In: Drug interactions. Greenwood Village (CO): IBM Watson Health; 2019 [diunduh 20 September 2020]. Tersedia dari: https://www.micro medexsolutions.com
Strandel J, Noren GK, Hagg S. Key elements in adverse drug interaction safety signals: An assessment of individual case safety reports. Drug Saf. 2013;36(1):63–70. doi: 10.1007/s40264-012-0003-9
U.S. Food and Drug Administration. Drug development and drug interactions: table of substrates, inhibitors and inducers [diunduh 25 Agustus 2020]. Tersedia dari: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers
Navid A, Ng DM, Wong SE, Lightstone FC. Application of a physiologically based pharmacokinetic model to study theophylline metabolism and its interaction with ciprofloxacin and caffeine. CPT Pharmacometrics Syst. Pharmacol. 2016;5(2):74–81. doi: 10.1002/psp4.12061
Khan S, Jones S, Preston CL. Theophylline interactions. Pharm J. 2014; 293(7818):52–4. doi: 10.1211/PJ.2021.1.84125
Davis S. Macrolides and ketolides: more than just antimicrobial. S Afr Pharm J. 2011;78(6):24–7.
DOI: https://doi.org/10.15416/ijcp.2021.10.2.127
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