BNF for Children 2011-2012

BNFC 2011–2012 6.7.3 Metyrapone 3916.7 Other endocrine drugs6.7.1 Bromocriptine and otherdopaminergic drugs6.7.2 Drugs affecting gonadotrophins6.7.3 Metyrapone6.7.4 Somatomedins6.7.1 Bromocriptine and otherdopaminergic drugsClassification not used in BNF for Children.6.7.2 Drugs affectinggonadotrophinspain, allergic skin reactions, hypoadrenalism, hirsutismLicensed use licensed for use in childrenIndication and doseDifferential diagnosis of ACTH-dependentCushing’s syndrome. By mouthChild 1 month–18 years 15 mg/kg (or 300 mg/m 2 ) every 4 hours for 6 doses; minimum dose250 mg every 4 hours, max. 750 mg every 4 hoursManagement of Cushing’s syndrome. By mouthRange 250 mg–6 g daily, adjusted according tocortisol production; see notes aboveMetopirone c (Alliance) ACapsules, ivory, metyrapone 250 mg, net price 100-tab pack = £38.88. Label: 21, counselling, drivingClassification not used in BNF for Children. See section6.4.2 for use in precocious puberty.6.7.4 Somatomedins6.7.3 MetyraponeMetyrapone is a competitive inhibitor of 11b-hydroxylationin the adrenal cortex; the resulting inhibition ofcortisol (and to a lesser extent aldosterone) productionleads to an increase in ACTH production which, in turn,leads to increased synthesis and release of cortisolprecursors. It is used as a test of anterior pituitaryfunction.Most types of Cushing’s syndrome are treated surgically.Metyrapone may be useful to control the symptomsof the disease or to prepare the child for surgery.The dosages used are either low, and tailored to cortisolproduction, or high, in which case corticosteroid replacementtherapy is also needed.Ketoconazole (section 5.2.2) is also used by specialistsfor the management of Cushing’s syndrome [unlicensedindication].METYRAPONECautions gross hypopituitarism (risk of precipitatingacute adrenal failure); hypertension on long-termadministration; hypothyroidism (delayed response);many drugs interfere with diagnostic estimation ofsteroids; avoid in acute porphyria (section 9.8.2)Skilled tasks Drowsiness may affect the performance ofskilled tasks (e.g. driving)Contra-indications adrenocortical insufficiency (seeCautions)Hepatic impairment use with caution (delayedresponse)Pregnancy avoid (may impair biosynthesis of fetalplacentalsteroids)Breast-feeding avoid—no information availableSide-effects occasional nausea, vomiting, dizziness,headache, hypotension, sedation; rarely abdominalSomatomedins are a group of polypeptide hormonesstructurally related to insulin and commonly known asinsulin-like growth factors (IGFs). Mecasermin, ahuman insulin-like growth factor-I (rhIGF-I), is the principalmediator of the somatotropic effects of humangrowth hormone and is used to treat growth failure inchildren with severe primary insulin-like growth factor-Ideficiency.MECASERMIN(Recombinant human insulin-like growth factor-I;rhIGF-I)Cautions correct hypothyroidism before initiatingtreatment; diabetes mellitus (adjustment of antidiabetictherapy may be necessary), monitor ECG beforeand on termination of treatment (and during treatmentif ECG abnormal), papilloedema (see underSide-effects), monitor for disorders of the epiphysis ofthe hip (monitor for limping), monitor for signs oftonsillar hypertrophy (snoring, sleep apnoea, andchronic middle ear effusions)Contra-indications evidence of tumour activity (discontinuetreatment)Pregnancy avoid unless essential; contraceptionadvised in women of child-bearing potentialBreast-feeding avoidSide-effects headache, funduscopy for papilloedemarecommended if severe or recurrent headache, visualproblems, nausea and vomiting occur—if papilloedemaconfirmed consider benign intracranial hypertension(rare cases reported); cardiomegaly, ventricularhypertrophy, tachycardia; convulsions, sleepapnoea, night terrors, dizziness, nervousness; tonsillarhypertrophy (see Cautions above); hypoglycaemia(especially in first month, and in younger children),hyperglycaemia, gynaecomastia; arthralgia, myalgia;visual disturbance, impaired hearing; antibody formation;injection-site reactions (rotate site)6 Endocrine system