Safety of octreotide in hospitalized infants

Highlights

• The safety profile of octreotide has not been described in infants.

• We examined diagnoses, laboratory abnormalities, and adverse events in this group.

• Few adverse events occurred during use of octreotide in our cohort of infants.

Abstract

Background

Octreotide is used off-label in infants for treatment of chylothorax, congenital hyperinsulinism, and gastrointestinal bleeding. The safety profile of octreotide in hospitalized infants has not been described; we sought to fill this information gap.

Methods

We identified all infants exposed to at least 1 dose of octreotide from a cohort of 887,855 infants discharged from 333 neonatal intensive care units managed by the Pediatrix Medical Group between 1997 and 2012. We collected laboratory and clinical information while infants were exposed to octreotide and described the frequency of baseline diagnoses, laboratory abnormalities, and clinical adverse events (AEs).

Results

A total of 428 infants received 490 courses of octreotide. The diagnoses most commonly associated with octreotide use were chylothorax (50%), pleural effusion (32%), and hypoglycemia (22%). The most common laboratory AEs that occurred during exposure to octreotide were thrombocytopenia (47/1000 infant-days), hyperkalemia (21/1000 infant-days), and leukocytosis (20/1000 infant-days). Hyperglycemia occurred in 1/1000 infant-days and hypoglycemia in 3/1000 infant-days. Hypotension requiring pressors (12%) was the most common clinical AE that occurred during exposure to octreotide. Necrotizing enterocolitis was observed in 9/490 (2%) courses, and death occurred in 11 (3%) infants during octreotide administration.

Conclusion

Relatively few AEs occurred during off-label use of octreotide in this cohort of infants. Additional studies are needed to further evaluate the safety, dosing, and efficacy of this medication in infants.

Introduction

Octreotide is a somatostatin analog that inhibits the release of growth hormone, glucagon, and insulin [1]. It decreases pancreatic secretion, gallbladder contraction, and gastrointestinal tract motility, and reduces intestinal blood flow by vasoconstriction of the splanchnic vessels [2], [3]. Through these effects on the gastrointestinal tract, octreotide reduces fat absorption and lymphatic flow in the thoracic duct [2].

In adults, it is labeled for use in the treatment of acromegaly, carcinoid tumors, and vasoactive intestinal peptide tumors [4]; additionally, octreotide is often used off-label for several other indications, including acute esophageal variceal bleeding, tumor growth stabilization, tumor linkage, treatment of idiopathic pulmonary fibrosis, and acute pancreatitis [5], [6], [7], [8], [9]. Although octreotide is not labeled for use in children, case reports, case series, and cohort studies document the use of octreotide in children for several indications, including pancreatitis, chylothorax, and gastrointestinal bleeding [10], [11], [12], [13], [14], [15], [16], [17], [18], [19]. In infants, the most common indication is treatment of congenital chylothorax, chylothorax secondary to thoracic surgery, congenital hyperinsulinism, and gastrointestinal bleeding [12], [13], [14]. Evidence of octreotide efficacy in this population is limited to small case series and retrospective studies [12], [15], [20].

The safety profile of octreotide has not been described in infants. In adults, the most frequent side effects are gastrointestinal events, glucose regulation disorders, hypothyroidism, and biliary tract abnormalities [4], [21]. Based on small studies in children, side effects associated with octreotide include hyperglycemia, hypoglycemia, hypertension, hyperbilirubinemia, diarrhea, abdominal cramping and pain, and necrotizing enterocolitis (NEC) [12], [15], [16], [22], [23]. In the present study, we describe the safety profile of octreotide in a cohort of hospitalized infants.