Drug Interactions between budesonide / formoterol and lonapegsomatropin

MONITOR: Human growth hormone may reduce the pharmacologic effects of corticosteroids. Growth hormone is thought to enhance the activity of CYP450 3A4, an enzyme involved in the catabolism of corticosteroids. In addition, growth hormone (GH) inhibits microsomal enzyme 11-beta-hydroxysteroid dehydrogenase type 1 (11BHSD-1), which is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. Consequently, individuals with untreated GH deficiency have relative increases in 11BHSD-1 and serum cortisol, and initiation of GH therapy may result in inhibition of 11BHSD-1 and reduced serum cortisol levels. Previously undiagnosed central (secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be required. In patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism, an increase in their maintenance or stress doses may be required following initiation of GH treatment. Cortisone acetate and prednisone may be affected more than others because conversion to their biologically active metabolites, cortisol and prednisolone, respectively, is dependent on the activity of 11BHSD-1.

MONITOR: Treatment with pharmacologic and supraphysiologic glucocorticoid dosages may attenuate the growth promoting effects of human growth hormone in children due to inhibition of the hypothalamic-pituitary-adrenal axis.

MANAGEMENT: Higher dosages of corticosteroids may be required during concomitant use of human growth hormone. Patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of GH treatment. In addition, glucocorticoid replacement dosing should be carefully adjusted in children receiving concomitant GH treatment to avoid both hypoadrenalism and an inhibitory effect on growth.

Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. However, clinical data are limited, and the potential significance is unknown. Patients who are receiving systemic or nebulized formulations of beta-2 agonists, high dosages of inhaled beta-2 agonists, or systemic corticosteroid therapy may be at a greater risk of developing hypokalemia.