BNF for Children 2011-2012

358 6.1.2 Antidiabetic drugs BNFC 2011–20126 Endocrine systemend of the adult dose range and then adjusted accordingto response.Metformin (section 6.1.2.2) is the oral antidiabetic drugof choice because there is most experience with thisdrug in children. If dietary changes and metformin donot control the diabetes adequately, either a sulfonylurea(section 6.1.2.1) or insulin (section 6.1.1) can beadded.Alternatively, oral therapy may be substituted with insulin.When insulin is added to oral therapy, it is generallygiven at bedtime as isophane or long-acting insulin, andwhen insulin replaces an oral regimen it may be given astwice-daily injections of a biphasic insulin (or isophaneinsulin mixed with soluble insulin), or a multiple injectionregimen. Weight gain and hypoglycaemia may becomplications of insulin therapy but weight gain can bereduced if the insulin is given in combination with metformin.Pregnancy and breast-feeding During pregnancy,women with pre-existing diabetes can be treated withmetformin [unlicensed use], either alone or in combinationwith insulin (section 6.1.1). Metformin can becontinued, or glibenclamide resumed, during breastfeedingfor those with pre-existing diabetes. Womenwith gestational diabetes may be treated, with or withoutconcomitant insulin (section 6.1.1), with glibenclamidefrom 11 weeks gestation (after organogenesis)[unlicensed use] or with metformin [unlicensed use].Women with gestational diabetes should discontinuehypoglycaemic treatment after giving birth.Other oral hypoglycaemic drugs are contra-indicated inpregnancy and breast-feeding.6.1.2.1 SulfonylureasThe sulfonylureas are not the first choice oral antidiabeticsin children. They act mainly by augmentinginsulin secretion and consequently are effective onlywhen some residual pancreatic beta-cell activity is present;during long-term administration they also have anextrapancreatic action. All can cause hypoglycaemia butthis is uncommon and usually indicates excessivedosage. Sulfonylurea-induced hypoglycaemia can persistfor many hours and must always be treated inhospital.Sulfonylureas are considered for children in whom metforminis contra-indicated or not tolerated. Severalsulfonylureas are available but experience in childrenis limited; choice is determined by side-effects and theduration of action as well as the child’s age and renalfunction. Glibenclamide, a long-acting sulfonylurea, isassociated with a greater risk of hypoglycaemia and forthis reason is generally avoided in children. Shorteractingalternatives, such as tolbutamide, may be preferred.Insulin therapy should be instituted temporarily duringintercurrent illness (such as coma, infection, and trauma).Sulfonylureas should be omitted on the morning ofsurgery; insulin is often required because of the ensuinghyperglycaemia in these circumstances.Sulfonylureas can be useful in the management ofcertain forms of diabetes that result from genetic defectsof beta-cell function; there is most experience withgliclazide.Cautions Sulfonylureas encourage weight gain andshould be prescribed only if poor control and symptomspersist despite adequate attempts at dieting; metformin(section 6.1.2.2) is considered the drug of choice inchildren.Contra-indications Sulfonylureas should be avoidedwhere possible in acute porphyria (section 9.8.2). Sulfonylureasare contra-indicated in the presence of ketoacidosis.Hepatic impairment Sulfonylureas should be avoidedor a reduced dose should be used in severe hepaticimpairment, because there is an increased risk of hypoglycaemia.Jaundice may occur.Renal impairment Sulfonylureas should be used withcare in those with mild to moderate renal impairment,because of the hazard of hypoglycaemia; they should beavoided where possible in severe renal impairment. Ifnecessary, the short-acting drug tolbutamide can beused in renal impairment, as can gliclazide which isprincipally metabolised in the liver, but careful monitoringof blood-glucose concentration is essential; care isrequired to use the lowest dose that adequately controlsblood glucose.Pregnancy The use of sulfonylureas in pregnancyshould generally be avoided because of the risk of neonatalhypoglycaemia; however, glibenclamide can beused during the second and third trimesters ofpregnancy in women with gestational diabetes, seesection 6.1.2.Breast-feeding The use of sulfonylureas (exceptglibenclamide [unlicensed use], see section 6.1.2) inbreast-feeding should be avoided because there is atheoretical possibility of hypoglycaemia in the infant.Side-effects Side-effects of sulfonylureas are generallymild and infrequent and include gastro-intestinaldisturbances such as nausea, vomiting, diarrhoea andconstipation.Sulfonylureas can occasionally cause a disturbance inliver function, which rarely leads to cholestatic jaundice,hepatitis, and hepatic failure. Hypersensitivity reactionscan occur, usually in the first 6–8 weeks of therapy. Theyconsist mainly of allergic skin reactions which progressrarely to erythema multiforme or exfoliative dermatitis,fever, and jaundice; photosensitivity has rarely beenreported with glipizide. Blood disorders are also rarebut include leucopenia, thrombocytopenia, agranulocytosis,pancytopenia, haemolytic anaemia, and aplasticanaemia.GLIBENCLAMIDECautions see notes above; interactions: Appendix 1(antidiabetics)Contra-indications see notes aboveHepatic impairment see notes aboveRenal impairment see notes abovePregnancy see notes above