No studies on the interactions with other drugs have been performed since recombinant somatropin has the same amino acid sequence as pituitary-derived growth hormone.
Cytochrome P450 (CYP450)-Metabolized Drugs
Limited published data indicate that growth hormone treatment increases cytochrome P450 (CP450) mediated antipyrine clearance in human. These data suggest that growth hormone administration may alter the clearance of compounds known to be metabolized by CP450 liver enzymes (e.g. corticosteroids, sex steroids, anticonvulsants, cyclosporine). Careful monitoring is advisable when growth hormone is administered in combination with other drugs known to be metabolized by CP450 liver enzymes.
β-Hydroxysteroid Dehydrogenase Type 1
The microsomal enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD-1) is required for conversion of cortisone to its active metabolite, cortisol, in hepatic and adipose tissue. GH and somatropin inhibit 11βHSD-1. Consequently, individuals with untreated GH deficiency have relative increases in 11βHSD-1 and serum cortisol. Introduction of somatropin treatment may result in inhibition of 11βHSD-1 and reduced serum cortisol concentrations. As a consequence, previously undiagnosed central (secondary) hypoadrenalism may be unmasked and glucocorticoid replacement may be required in patients treated with somatropin. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment; this may be especially true for patients treated with cortisone acetate and prednisone since conversion of these drugs to their biologically active metabolites is dependent on the activity of 11βHSD-1.
Concomitant glucocorticoid treatment may inhibit the growth promoting effect of human growth hormone. GHD children with coexisting ACTH deficiency should have their glucocorticoid replacement dose carefully adjusted to avoid an inhibitory effect on growth. Therefore, patients treated with glucocorticoids should have their growth monitored carefully to assess the potential impact of glucocorticoid treatment on growth. (see WARNINGS AND PRECAUTIONS – Endocrine and Metabolism and DRUG INTERACTIONS - β-Hydroxysteroid Dehydrogenase Type 1)
Patients with ACTH deficiency should be carefully monitored to avoid adrenal insufficiency.
In patients on oral estrogen replacement, a larger dose of somatropin may be required to achieve the defined treatment goal. If a woman taking somatropin begins oral estrogen therapy, the dose of somatropin may need to be increased to maintain the serum insulin-like growth factor-I (IGF-I) levels within the normal age-appropriate range. However, the maximum recommended weekly dose should not be exceeded.
If a woman on somatropin discontinues oral estrogen therapy, the dose of somatropin may need to be reduced to avoid excess of growth hormone and/or side effects.
Insulin and/or Oral/Injectable Hypoglycemic Agents
In patients with diabetes mellitus requiring drug therapy, the dose of insulin and/or oral/injectable agent may require adjustment when somatropin therapy is initiated (see WARNINGS AND PRECAUTIONS).