GUEST COLUMN

Somatostatin or Sandostatin?

By Linh P. Barclay, PharmD
University of Florida College of Pharmacy Shands Hospital AGH, Gainesville

The confusion between somatostatin and Sandostatin usually arises when somatostatin is prescribed, when in fact the drug that is actually being requested is the somatostatin analogue, octreotide. Adding to the problem, the brand name of octreotide (Sandostatin) sounds and looks similar to somatostatin.

Somatostatin was first identified in 1968 as a substance that inhibited the pituitary secretion of growth hormone (GH) in rats. Also, somatostatin inhibited the release of other pituitary hormones (i.e., thyrotropin, prolactin) and suppressed both exocrine and endocrine functions of the gastro-entero-pancreatic system. In humans, prolonged intravenous infusion of somatostatin inhibits GH, thyrotropin, insulin, glucagen, and basal and gastrin-stimulated gastric acid secretion.

Somatostatin affects the absorption, motility, splanchnic blood flow, and trophic functions of the GI tract. In clinical studies, somatostatin inhibited peptide secretion and was shown to produce rapid symptomatic improvement in patients with acro megaly, insulinomas, glucagonomas, carcinoid tumors and vasoactive intestinal polypeptide-secreting tumors (VIPomas), nontumoral secretory diarrhea, and gastrointestinal bleeding.

However, the usefulness of somatostatin is limited by its short duration of action and lack of selectivity. Its use has lead to rebound hypersecretion of GH and other substances following cessation of somatostatin infusion. Also, long-term use of somatostatin may result in intestinal malabsorption and glucose intolerance.

Somatostatin is an orphan drug manufactured by Ferring Laboratories of Tarrytown, NY, under the trade name Reducin. Octreotide (Sandostatin) is a long-acting synthetic analogue of somatostatin. It has similar qualitative effects, but differs in potency and selectivity for target issues. Octre o tide can suppress the secretion of serotonin, VIP, gastrin, insulin, glucagon, GH, secretin, motilin, and pancreatic polypeptide. Octreotide also exerts effects on GI function by prolonged intestinal tran sit time, regulating intestinal water and electrolyte transport, and decreasing splanchnic blood flow. In 1988, octreotide was approved by the FDA for use in the treatment of malignant carcinoid syndrome and VIP-secreting tumors. This, however, was considered by many to be only a "beachhead" indication. Based on its pharmacology, the anticipated use of octreotide is much more varied.

Preclinical studies comparing octreotide with somatostatin have indicated that octreotide is 70 times more potent in inhibiting the release of GH, 23 times more potent in glucagon inhibition, and three times more potent in insulin inhibition. In humans, octreotide is approximately 20 times more potent than somatostatin in the inhibition of GH secretion. Octreotide is highly selective for target cells, with less effect on insulin secretion compared with its effect on GH and glucagon.

Somatostatin given by continuous IV

One important drawback of the clinical application of somatostatin is its very short biological half-life of one to three minutes. This requires that somatostatin be given by continuous IV infusion. Octreotide is more resistant to tissue and serum peptidases. This, combined with higher receptor affinity, increases octreotide’s elimination half-life to approximately one and one-half hours and prolongs the duration of action of six to 12 hours. Although somatostatin must be administered by continuous infusion, octreotide may be given by subcutaneous injection of IV bolus.

The most frequent adverse reactions associated with both agents involve the GI system. These include diarrhea, steatorrhea, abdominal pain, nausea, vomiting, hypochlorhydria, and mild malabsorption. Most cases are mild to moderate in severity and tend to decrease over time. There are reports of central nervous system effects such as dizziness, headache, weakness, fatigue, blurred vision, and anxiety with octreotide. Octreotide is associated with less rebound hypersecretion of hormones when its effect tapers off, but hypoglycemia may be seen following octreotide and somatostatin administration.

Compared with somatostatin, octreotide produces a less marked hypoglycemia, less inhibition of splanchnic glucose output, and a diminished rebound phenomenon after infusion. The duration of insulin suppression is shorter following chronic therapy. No rebound hypersecretion of GH is seen following administration of octreotide in contrast to somatostatin withdrawal. In a prospective study, baseline thyroid hormone levels, thyroid-stimulating hormone, cortisol, and gonadotropins were not altered by octreotide.

However, there has been a report of hypothyroidism with octreotide. Several cases of cholelithiasis or cholecystitis associated with chronic octreo - tide administration have been reported. Somato statin may transiently increase blood pressure and pulse slightly. Ventricular premature systoles have been seen in patients treated with somatostatin. However, no adverse cardiac effects have been reported with octreotide.

Dosages differ for the two drugs

Problems could occur when somatostatin is prescribed inadvertently instead of octreotide. Because of octreotide’s greater potency and selectivity, lower dosages are required when this drug is used. For example, when used acutely to treat patients with bleeding esophageal varices, somatostatin is usually administered with a 250 mg bolus, followed by 250 mg/hr continuous IV infusion. Octreotide is generally infused at 5 mg to 100 mg/hr for this use.

A higher dose of octreotide may increase the chances of a patient experiencing significant adverse reactions, such as hypoglycemia. Though not as likely, somatostatin administered by the incorrect route (i.e., IV bolus or subQ) probably would not be effective. If octreotide is prescribed using somatostatin’s dosage, it would be very expensive. For instance, if octreotide is given for esophageal varices at somatostatin dosages (i.e., 250 mg bolus and 250 mg/hr for six hours), the patient charge is $567, substantially more than that for conventional doses of octreotide ($214).

There is also a logistical problem. Somatostatin must be obtained through the Drug Orphan Program. When octreotide is prescribed, it is readily available. To minimize the confusion between somatostatin and octreotide, physicians should specify octreotide, rather than the trade name Sandostatin, and the two should not be used interchangeably. Likewise, when evaluating these agents in the literature, the drug being used, and the corresponding dose should be confirmed.

[For more information, call Barclay at (352) 372-4321.]