Octreotide Acetate (octreotide acetate)

Octreotide, a somatostatin analog, is a synthetic polypeptide that is pharmacologically related to the natural hormone somatostatin.

Octreotide is a synthetic octapeptide pharmacologically related to the natural hormone somatostatin; it is also known as a somatostatin analog. Octreotide is a more potent inhibitor of growth hormone (GH), glucagon, and insulin than somatostatin. Octreotide also suppresses luteinizing hormone (LH) response to gonadotropin-releasing hormone (GnRH), decreases splanchnic blood flow, and inhibits release of serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide.

Because of the drug's pharmacologic actions, octreotide has been employed to control gastrointestinal and other manifestations associated with a variety of conditions (e.g., flushing and diarrhea associated with metastatic carcinoid tumors, watery diarrhea associated with VIP-secreting adenomas). Octreotide decreases the concentration of GH and/or insulin-like growth factor 1 (IGF-1) in patients with acromegaly.

Octreotide immediate-release injection (Sandostatin(R) injection and generic equivalents) is absorbed rapidly and completely following subcutaneous injection; peak concentrations are reached in 0.4 hours (0.7 in those with acromegaly). IV and subcutaneous doses were found to be bioequivalent. Octreotide is 65% bound in the plasma (41.2% in those with acromegaly), mainly to lipoprotein and to a lesser extent,to albumin.

The elimination half-life of the drug is 1.7-1.9 hours and approximately 32% of the dose is excreted unchanged in the urine. The duration of action of immediate-release octreotide is variable but extends up to 12 hours depending on the type of tumor, necessitating multiple daily dosing with this dosage form.

Octreotide half-life is longer (2.4-3.1 hours compared to 1.9 hours)in patients with renal impairment (creatinine clearance <= 60 mL/minute); in those requiring dialysis, clearance is reduced by half compared to healthy volunteers. In patients with liver impairment such as cirrhosis and fatty liver, octreotide half-life is increased to 3.7 and 3.4 hours, respectively.

Octreotide long-acting release (LAR) injectable suspension for IM administration (Sandostatin(R) LAR Depot) is a long-acting dosage form consisting of microspheres of the biodegradable glucose star polymer, D,L-lactic and glycolic acids copolymer, containing octreotide. All of the clinical and pharmacological characteristics of the immediate-release dosage form (Sandostatin(R) Injection and generic equivalents) are maintained with the added feature of slow release of octreotide from the site of injection, reducing the need for frequent administration. This slow release occurs as the polymer biodegrades, primarily through hydrolysis.

The relative bioavailability of the long-acting suspension compared to the immediate-release solution given subcutaneously was 60-63%. Following a single IM injection in healthy volunteers,serum octreotide concentrations reach a transient initial peak within 1 hour which progressively declines for the next 3-5 days. Following this decline, octreotide concentrations increase slowly, plateau in approximately 2-3 weeks post-injection, and are maintained over a period of nearly 2-3 additional weeks.

Following multiple IM injections given every 4 weeks, steady-state octreotide concentrations are achieved after the third injection. The long-acting suspension has not been studied in patients with renal or hepatic impairment.

Octreotide delayed-release capsules (Mycapssa(R)) are enteric-coated (methacrylate (Acryl-EZE(R))) and utilize Transient Permeability Enhancer (TPE(R)) technology. The capsules are designed to pass through the stomach intact and disintegrate when it reaches the higher pH of the small intestine where the octreotide-TPE formulation is released into the lumen. TPE facilitates paracellular transit across the intestinal wall via transient and reversible opening of the tight junctions between cells, allowing intact octreotide to be absorbed.

The delayed-release preparation does not cause any chemical or physical change in the active compound and once octreotide reaches the systemic circulation, the metabolism and excretion of octreotide is expected to be identical to that of the immediate-release dosage form (Sandostatin Injection and generic equivalents). In a study designed to assess the duration of Mycapssa(R)-induced increased intestinal permeability, an increase in paracellular permeability was observed 2 hours after administration and returned to baseline by 5.5 hours after administration; this permeability is completely reversible within this timeframe. When comparing a single dose of subcutaneous immediate-release octreotide to a single dose of oral octreotide (Mycapssa(R)), absorption time was longer, peak concentrations were reached at a median 1.67-2.5 hours (oral) versus 0.5 hours (subcutaneous), and peak octreotide levels were 33% lower in healthy subjects receiving the oral preparation.

In patients with acromegaly, octreotide concentrations are dose proportional following chronic administration of the oral preparation (40, 60, or 80 mg total daily dose); mean peak plasma concentrations were lower compared to single-dose peak concentrations in healthy subjects. Administration of the oral preparation with food decreases the rate and extent of absorption by 90% in healthy subjects. In patients with acromegaly, elimination after chronic dosing of the oral preparation was slightly slower than that seen in healthy subjects, with a mean apparent half-life at steady state ranging from 3.2-4.5 hours across all doses (20 mg, 40 mg, 60 mg, and 80 mg).

Elimination is complete approximately 48 hours after the last dose in patients who have achieved steady-state plasma levels; minimal accumulation (approximately 10%) was observed in patients after repeat administration of the oral preparation. In patients with severe renal impairment (estimated glomerular filtration rate 15-19 mL/minute per 1.73 m2), octreotide AUC and half-life are increased, but not to the same extent as matched-controls requiring dialysis. In patients with end stage renal disease requiring dialysis, clearance is reduced 46%, AUC is increased 87%, and the half-life increased 85% compared to healthy subjects.

USES: Octreotide is used to treat severe watery diarrhea and sudden reddening of the face and neck caused by certain types of tumors (such as carcinoid tumors, vasoactive intestinal peptide tumors) that are found usually in the intestines and pancreas. The symptoms occur when these tumors make too much of certain natural substances (hormones). This medication works by blocking the production of these hormones.

By decreasing watery diarrhea, octreotide helps to reduce the loss of body fluids and minerals. Octreotide is also used to treat a certain condition (acromegaly) that occurs when the body makes too much of a certain natural substance called growth hormone. Treating acromegaly helps reduce the risk of serious problems such as diabetes and heart disease.

Octreotide works by decreasing how much growth hormone your body makes. This drug is not a cure for these conditions. This medication is usually used with other treatment (such as surgery, radiation, other drugs).

Generic name: octreotide acetate
Pronunciation: (ok-TREE-oh-tide)

The following indications are listed for Octreotide Acetate:

• Acromegaly
• Carcinoid Syndrome
• Diarrhea Associated With Vasoactive Intestinal Peptide (Vip)-Secreting Tumor

Also known as: Acromegalia, Diarrhea Associated With Vasoactive Intestinal Peptide (Vip)-Producing Tumor, Diarrhea Associated With Vasoactive Intestinal Peptide Tumor, Diarrhea Associated With Vipoma, Malignant Carcinoid Syndrome, Marie's Disease, Marie's Syndrome, Metastatic Carcinoid Syndrome.

No ICD codes are available for this drug.