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Indian Pediatr 2013;50: 342-343 |
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Prolonged Sedation Following Administration of
Oral Midazolam
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Thirunavukkarasu Arun Babu
Assistant Professor of Pediatrics, Indira Gandhi
Medical College and
Research Institute (IGMC&RI), Pondicherry 605 010, India .
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Midazolam is a commonly used drug for procedural sedation in
children due to its rapid onset, short duration of action
and hemodynamic stability, which may be associated with
improved patient acceptance. It is also associated with
shorter recovery time and minimal risk of vomiting and
respiratory depression, making it the drug of choice for
conscious sedation in pediatric patients. We report an
unusual drug interaction between midazolam and azithromycin
leading to prolonged sedation in a child.
A 2-year-old male child presented with
laceration in the thigh after falling down from bicycle.
There was no evidence of head injury or injury to any
internal organs. X-ray of thigh did not reveal any
fractures. Suturing was planned after giving local
anesthesia. One milligram of parenteral preparation of
midazolam (0.1 mg/kg) was given orally as a premedication
for sedation. Procedure was successfully completed. The
child continued to remain sedated even after the procedure.
The child was monitored in intensive care overnight. He was
hemodynamically stable throughout and there was no evidence
of respiratory depression. Though the child was arousable,
he slipped into sleep immediately after that. Child regained
consciousness the next day, but remained drowsy. We could
not identify the cause of this unexplained prolonged
drowsiness. Detailed history revealed that the child had
fever for 3 days for which he had been prescribed oral
azithromycin by a practitioner. The dose of 200 mg once
daily (20 mg/kg) was given as syrup formulation for 3 days
before oral midazolam was given. The patient was discharged
the next day and was normal at follow up for suture removal.
Literature search revealed the
possibility of drug interaction between midazolam and
macrolides, erthyromycin in particular, an inhibitor of
CYP3A which is a cytochrome P450 isoform responsible for
midazolam hydroxylation [1].
There are reports of drug interaction between
erythromycin and oral midazolam, leading to prolonged
sedation [2]. Such interaction is also possible with
azithromycin [1].
Azithromycin has not been found to increase
the plasma concentrations of oral midazolam in few studies
[3,4], though
both these studies were done on healthy adult volunteers and
not in children. The chance of drug interaction is minimal
with intravenous midazolam since it bypasses the altered
presystemic metabolism and its pharmacokinetics is not
affected to the same extent as after oral administration
[5]. As azithromycin is commonly prescribed in pediatric
patients, physicians should be aware of this possible drug
interaction with oral midazolam. If midazolam has to be used
with macrolides, intravenous route should be preferred.
References
1. Ito K, Ogihara K, Kanamitsu S, Itoh T.
Prediction of the in vivo interaction between
midazolam and macrolides based on in vitro studies
using human liver microsomes. Drug Metab Dispos.
2003;31:945-54.
2. Senthilkumaran S, Subramanian PT.
Prolonged sedation related to erythromycin and midazolam
interaction - a word of caution. Indian Pediatr.
2011;48:909.
3. Mattila MJ, Vanakoski J,
Idänpään-Heikkilä JJ. Azithromycin does not alter the
effects of oral midazolam on human performance. Eur J Clin
Pharmacol. 1994;47:49-52.
4. Backman JT, Olkkola KT, Neuvonen PJ.
Azithromycin does not increase plasma concentrations of oral
midazolam. Int J Clin Pharmacol Ther. 1995;33:356-9.
5. Olkkola KT, Aranko K, Luurila H, Hiller A, Saarnivaara
L, Himberg JJ, et al. A potentially hazardous
interaction between erythromycin and midazolam. Clin
Pharmacol Ther. 1993;53:298-305.
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