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    Neonatal Intensive Care Drug Manual




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    Pharmacokinetics: Not reported in newborns or children. Long half-life in adults (48 hours), 94% protein bound (albumin), and renally excreted.10, 11 Albumin binding and renal clearance of diazoxide reduced in renal failure.12 (LOE – none in infants)

    Safety: High rate of reported complications: Total 37%; circulatory complications 19%; oedema 17%; oliguria 5%; reopening of the ductus arteriosus 4%; hypertrichosis 15%; hyperkalaemia 4%; deterioration of liver function 1%; others 8%.3 (LOE IV, GOR C).

    Practice points




    References

    1. Tas E, Mahmood B, Garibaldi L, Sperling M. Liver injury may increase the risk of diazoxide toxicity: a case report. European journal of pediatrics. 2015;174:403-6.

    2. Arnoux JB, Verkarre V, Saint-Martin C, Montravers F, Brassier A, Valayannopoulos V, Brunelle F, Fournet JC, Robert JJ, Aigrain Y, Bellanne-Chantelot C, de Lonlay P. Congenital hyperinsulinism: current trends in diagnosis and therapy. Orphanet journal of rare diseases. 2011;6:63.

    3. Yoshida K, Kawai M, Marumo C, Kanazawa H, Matsukura T, Kusuda S, Yorifuji T, Heike T. High prevalence of severe circulatory complications with diazoxide in premature infants. Neonatology. 2014;105:166-71.

    4. Banerjee I, Avatapalle B, Padidela R, Stevens A, Cosgrove KE, Clayton PE, Dunne MJ. Integrating genetic and imaging investigations into the clinical management of congenital hyperinsulinism. Clinical endocrinology. 2013;78:803-13.

    5. Senniappan S, Shanti B, James C, Hussain K. Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management. Journal of inherited metabolic disease. 2012;35:589-601.

    6. Padidela R, Fiest M, Arya V, Smith VV, Ashworth M, Rampling D, Newbould M, Batra G, James J, Wright NB, Dunne MJ, Clayton PE, Banerjee I, Hussain K. Insulinoma in childhood: clinical, radiological, molecular and histological aspects of nine patients. European journal of endocrinology / European Federation of Endocrine Societies. 2014;170:741-7.

    7. Hu S, Xu Z, Yan J, Liu M, Sun B, Li W, Sang Y. The treatment effect of diazoxide on 44 patients with congenital hyperinsulinism. Journal of pediatric endocrinology & metabolism : JPEM. 2012;25:1119-22.

    8. Flanagan SE, Patch AM, Locke JM, Akcay T, Simsek E, Alaei M, Yekta Z, Desai M, Kapoor RR, Hussain K, Ellard S. Genome-wide homozygosity analysis reveals HADH mutations as a common cause of diazoxide-responsive hyperinsulinemic-hypoglycemia in consanguineous pedigrees. The Journal of clinical endocrinology and metabolism. 2011;96:E498-502.

    9. Shi Y, Avatapalle HB, Skae MS, Padidela R, Newbould M, Rigby L, Flanagan SE, Ellard S, Rahier J, Clayton PE, Dunne MJ, Banerjee I, Cosgrove KE. Increased plasma incretin concentrations identifies a subset of patients with persistent congenital hyperinsulinism without KATP channel gene defects. The Journal of pediatrics. 2015;166:191-4.

    10. Kirsten R, Nelson K, Kirsten D, Heintz B. Clinical pharmacokinetics of vasodilators. Part I. Clinical pharmacokinetics. 1998;34:457-82.

    11. Ogilvie RI, Nadeau JH, Sitar DS. Diazoxide concentration-response relation in hypertension. Hypertension. 1982;4:167-73.

    12. Pearson RM. Pharmacokinetics and response to diazoxide in renal failure. Clinical pharmacokinetics. 1977;2:198-204.

    13. Australian Injectable Drugs Handbook, 6th Edition, Society of Hospital Pharmacists of Australia 2014.

    14. Gray KD, Dudash K, Escobar C, Freel C, Harrison T, McMillan C, Puia-Dumitrescu M, Cotten CM, Benjamin R, Clark RH, Benjamin DK. Prevalence and safety of diazoxide in the neonatal intensive care unit. Journal of Perinatology. 2018 Nov;38(11):1496-502.

    15. Welters A, Lerch C, Kummer S, Marquard J, Salgin B, Mayatepek E, Meissner T. Long-term medical treatment in congenital hyperinsulinism: a descriptive analysis in a large cohort of patients from different clinical centers. Orphanet journal of rare diseases. 2015 Dec 1;10(1):150.



    Original version Date: 6/10/2016

    Author: NeoMed Consensus Group

    Current Version number: 2

    Current Version Date: 6-11-2020

    Risk Rating: Low

    Due for Review: 6-11-2025

    Approved by: DTC

    Approval Date: TBA




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    Neonatal Intensive Care Drug Manual

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