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Assessing efficacy and safety of buccally inoculated midazolam and intravenously administered diazepam for relieving pediatric primary generalized epileptic seizures

https://doi.org/10.17749/2077-8333/epi.par.con.2021.088

Full Text:

Abstract

Objective: to confirm a therapeutic equivalence and similar safety profile of “Midazolam, oromucosal (buccal) solution” and “Sibazon, solution for intravenous and intramuscular administration” used in children aged from 1 year to 18 years suffering from primary generalized and bilateral tonic, clonic and tonic-clonic seizures.

Material and methods. An open-label, randomized clinical trial on efficacy and safety was conducted with 25 patients having primary generalized and bilateral tonic, clonic and tonic-clonic seizures due to epilepsy or epileptic syndrome. The study used age-appropriate doses of Midazolam with a single buccal administration as well as diazepam (Sibazon) for single intramuscular administration. Midazolam dosing was as follows: 5 mg for children of the younger age group (1 tube-dropper 5 mg/ml), 7.5 mg for children of the middle age group (1 tube-dropper 5 mg/ml and 1 tube-dropper 2.5 mg/ml), 10 mg for older children (2 tube-droppers 5 mg/ml). The drug effectiveness was assessed by primary and secondary criteria. The number of cases of drug administration in each group was used as the primary criteria, in which the convulsions ended up within 10 minutes after using the drug and did not resume within 60 minutes after drug administration. The following criteria were used as secondary: no repeated convulsive seizures within 24 hours after drug administration, no repeated convulsive seizure within 48 hours after drug administration, time before repeated convulsive seizure within 48 hours after drug administration. Clinical assessment was carried out according to clinical data, electroneurophysiologic (electroencephalographic) studies, electrocardiography, clinical blood and urine tests, aswell as biochemical blood tests by measuring glucose, total protein, albumin, total bilirubin, cholesterol, aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, alkaline phosphatase, creatinine, urea, and creatinine clearance level.

Results. Compliance with the first efficacy criterion after using Midazolam and Sibazon was observed in 11 (84.6%) and 9 (75%) patients in Group 1 and Group 2, respectively, showing insignificant differences (Fisher's exact test (FET): p=0.645). The number of no cases of repeated convulsive seizure within 24 hours after drug administration differed significantly and was 12 (92.3%) and 6 (50%), respectively (FET: p=0.030). The number of cases with no second seizures within 48 hours after drug administration in Group 1 and Group 2 was 12 (92.3%) and 5 (41.7%), respectively, showing insignificant differences (FET: p=0.0112). No serious adverse events were reported during the study. No patients cancelled participation in the study due to developed adverse event.

Conclusion. The data obtained evidence about compatibility of therapeutic efficacy profile and similar safety profile for “Midazolam, oromucosal (buccal) solution” and “Sibazon, solution for intravenous and intramuscular administration” that agrees with multiple data of earlier studies.

About the Authors

A. G. Prityko
Voyno-Yasenetskiy Scientific and Practical Center of Specialized Medical Care for Children
Russian Federation

Andrey G. Prityko – Dr. Med. Sc., Professor, Academician of Russian Academy of Natural Sciences, Director, Voyno-Yasenetskiy Scientific and Practical Center of Specialized Medical Care for Children

RSCI SPIN-code: 5045-6357

38 Aviators Str., Moscow 119619



K. V. Osipova
Voyno-Yasenetskiy Scientific and Practical Center of Specialized Medical Care for Children
Russian Federation

Karine V. Osipova – MD, PhD, Head of Department of Psychoneurology

38 Aviators Str., Moscow 119619



P. L. Sokolov
Voyno-Yasenetskiy Scientific and Practical Center of Specialized Medical Care for Children
Russian Federation

Pavel L. Sokolov – Dr. Med. Sc., Leading Researcher

38 Aviators Str., Moscow 119619



E. A. Ezhova
Moscow Endocrine Plant
Russian Federation

Ekaterina A. Ezhova – Deputy Director General for the Development of Medicines

25 Novokhokhlovskaya Str., Moscow 109052



I. G. Kotel’nikova
Moscow Endocrine Plant
Russian Federation

Irina G. Kotel’nikova – PhD (Pharm.), Head of Medical Department

25 Novokhokhlovskaya Str., Moscow 109052



E. G. Lukyanova
Voyno-Yasenetskiy Scientific and Practical Center of Specialized Medical Care for Children
Russian Federation

Ekaterina G. Lukyanova

38 Aviators Str., Moscow 119619



G. A. Osipova
Voyno-Yasenetskiy Scientific and Practical Center of Specialized Medical Care for Children
Russian Federation

Gayane A. Osipova

38 Aviators Str., Moscow 119619



References

1. Bastos F., Cross J.H. Epilepsy. Handb Clin Neurol. 2020; 174: 137–58. https://doi.org/10.1016/B978-0-444-64148-9.00011-9.

2. Ashrafi M.R., Khosroshahi N., Karimi P., et al. Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children. Eur J Paediatr Neurol. 2010; 14 (5): 434–8. https://doi.org/10.1016/j.ejpn.2010.05.009.

3. Yoshinaga H., Benitez A., Takeda S., et al. A Phase 3 open-label study of the efficacy, safety and pharmacokinetics of buccally administered midazolam hydrochloride for the treatment of status epilepticus in pediatric Japanese subjects. Epilepsy Res. 2021; 174: 106651. https://doi.org/10.1016/j.eplepsyres.2021.106651.

4. Mpimbaza A., Ndeezi G., Staedke S., et al. Comparison of buccal midazolam with rectal diazepam in the treatment of prolonged seizures in Ugandan children: a randomized clinical trial. Pediatrics. 2008; 121 (1): e58-64. https://doi.org/10.1542/peds.2007-0930.

5. Garnock-Jones K.P. Oromucosal midazolam: a review of its use in pediatric patients with prolonged acute convulsive seizures. Paediatr Drugs. 2012; 14 (4): 251–61. https://doi.org/10.2165/11209320-000000000-00000.

6. McTague A., Martland T., Appleton R. Drug management for acute tonic-clonic convulsions including convulsive status epilepticus inchildren. Cochrane Database Syst Rev. 2018; 1 (1): CD001905. https://doi.org/10.1002/14651858.CD001905.pub3.

7. Midazolam oral transmucosal route. An alternative to rectal diazepam for some children. Prescrire Int. 2013; 22 (140): 173–7.

8. McIntyre J., Robertson S., Norris E., et al. Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet. 2005; 366 (9481): 205–10. https://doi.org/10.1016/S0140-6736(05)66909-7.

9. Soroushnia A., Ganji F., Vasheghani-Farahani E., Mobedi H. Preparation, optimization, and evaluation of midazolam nanosuspension: enhanced bioavailability for buccal administration. Prog Biomater. 2021; 10 (1): 19–28. https://doi.org/10.1007/s40204-020-00148-x.

10. Scott L.J., Lyseng-Williamson K.A., Garnock-Jones K.P. Oromucosal midazolam: a guide to its use in paediatric patients with prolonged acute convulsive seizures. CNS Drugs. 2012; 26 (10): 893–7. https://doi.org/10.2165/11209350-000000000-00000.

11. De Boer A.G., de Leede L.G., Breimer D.D. Drug absorption by sublingual and rectal routes. Br J Anaesth. 1984; 56 (1): 69–82. https://doi.org/10.1093/bja/56.1.69.

12. Walberg E.J., Wills R.J., Eckhert J. Plasma concentrations of midazolam in children following intranasal administration. Anesthesiology. 1991; 74 (2): 233–5. https://doi.org/10.1097/00000542-199102000-00007.

13. Appleton R., Sweeney A., Choonara I., et al. Lorazepam versus diazepam in the acute treatment of epileptic seizures and status epilepticus. Dev Med Child Neurol. 1995; 37 (8): 682–8. https://doi.org/10.1111/j.1469-8749.1995.tb15014.x.

14. Chamberlain J.M., Altieri M.A., Futterman C., et al. A prospective, randomized study comparing intramuscular midazolam with intravenous diazepam for the treatment of seizures in children. Pediatr Emerg Care. 1997; 13 (2): 92–4. https://doi.org/10.1097/00006565-199704000-00002.


For citation:


Prityko A.G., Osipova K.V., Sokolov P.L., Ezhova E.A., Kotel’nikova I.G., Lukyanova E.G., Osipova G.A. Assessing efficacy and safety of buccally inoculated midazolam and intravenously administered diazepam for relieving pediatric primary generalized epileptic seizures. Epilepsy and paroxysmal conditions. 2021;13(2):97-105. (In Russ.) https://doi.org/10.17749/2077-8333/epi.par.con.2021.088

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ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)