Side Effects of Sandostatin (octreotide acetate)

Sandostatin (octreotide acetate) is an injectable medicine used to treat acromegaly and to treat severe diarrhea and flushing caused by some hormone-secreting cancers.

It is similar to the hormone somatostatin, which is naturally produced in the body that has several effects including inhibition of the release of hormones. Sandostatin works in a similar fashion as somatostatin, but is degraded more slowly and is a stronger inhibitor of glucagon, growth hormone, and insulin release.

Like somatostatin, Sandostatin also decreases the release of growth stimulating hormones, decreases blood flow to the digestive organs, and inhibits the release of digestive hormones such as serotonin, gastrin, vasoactive intestinal peptide, secretin, motilin, and pancreatic polypeptide which helps treat symptoms of severe diarrhea and flushing.

Acromegaly is a rare hormonal disorder in which there is an overproduction of growth hormone that leads to the abnormal growth of the hands, feet, or facial features.

Sandostatin significantly decreases the levels of growth hormone and IGF-I (somatomedin C) in patients with acromegaly. Other actions of Sandostatin include suppression of thyroid stimulating hormone (TSH) release, inhibition of gallbladder contractility, and the secretion of bile.

Common side effects of Sandostatin include

• gallbladder problems,
• slow heart rate,
• irregular heartbeat (arrhythmias),
• diarrhea,
• nausea,
• stomach pain,
• vomiting,
• gas (flatulence),
• abnormal stools,
• stomach distention,
• constipation,
• low and high blood glucose,
• low thyroid levels,
• headache, and
• injection site pain.

Serious side effects of Sandostatin include pancreatitis.

Drug interactions of Sandostatin include some orally taken medications because Sandostatin can alter nutrient absorption and may interfere with their absorption.

• Use of Sandostatin with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection.
• Dose adjustments may be required for some medications including insulin, oral anti-diabetes medicines, beta-blockers, calcium channel blockers, and agents used to control fluid and electrolyte balance if taken with Sandostatin.
• Sandostatin may decrease the removal of certain drugs broken down by the CYP3A4 liver enzymes and should be used cautiously with other drugs that are extensively metabolized by these enzymes or those that have a low therapeutic index.
• Co-administration of Sandostatin and bromocriptine may increase the blood levels of bromocriptine.

There are no adequate and well-controlled studies of Sandostatin use in pregnancy. Sandostatin should be used in pregnancy only if clearly needed.

It is unknown if Sandostatin can enter breast milk. As many drugs can enter human milk and cause side effects in the nursing infant, Sandostatin should be used cautiously during breastfeeding.

Side effects reported with octreotide include:

• gallbladder problems,
• slow heart rate (bradycardia),
• irregular heartbeat (arrhythmias),
• diarrhea,
• nausea,
• stomach pain,
• vomiting,
• gas (flatulence),
• abnormal stools,
• stomach distention,
• constipation,
• low and high blood glucose,
• low thyroid levels,
• headache,
• injection site pain, and
• pancreatitis.

Other side effects that occurred in 1% to 4% of patients included:

• weakness,
• tiredness,
• itching,
• joint pain,
• backache,
• urinary tract infection (UTI),
• cold symptoms,
• flu symptoms,
• injection site hematoma,
• bruising,
• edema,
• flushing,
• blurred vision,
• fat malabsorption,
• hair loss,
• visual disturbance, and
• depression.

Other side effects include:

• hepatitis,
• jaundice,
• increase in liver enzymes,
• gastrointestinal (GI) bleeding,
• hemorrhoids,
• appendicitis,
• gastric or peptic ulcer,
• gallbladder polyp,
• rash,
• superficial skin infections,
• petechiae,
• hives,
• basal cell carcinoma (skin cancer),
• arthritis,
• joint effusion,
• muscle pain,
• Raynaud's phenomenon,
• chest pain,
• shortness of breath,
• thrombophlebitis,
• ischemia,
• congestive heart failure,
• high blood pressure,
• hypertensive reaction,
• heart palpitations,
• orthostatic hypotension,
• tachycardia,
• anxiety,
• low sex drive (low libido),
• fainting (syncope),
• tremors,
• seizure,
• vertigo,
• Bell's Palsy,
• paranoia,
• pituitary apoplexy,
• increased intraocular pressure,
• amnesia,
• hearing loss,
• neuritis,
• pneumonia,
• pulmonary nodule,
• status asthmaticus,
• galactorrhea,
• hypoadrenalism,
• diabetes insipidus,
• gynecomastia,
• amenorrhea,
• polymenorrhea,
• oligomenorrhea,
• vaginitis,
• nephrolithiasis,
• hematuria,
• anemia,
• iron deficiency,
• epistasis,
• ear infection (otitis),
• allergic reaction,
• increased creatine kinase, and
• weight loss.

Gallbladder Abnormalities

Gallbladder abnormalities, especially stones and/or biliary sludge, frequently develop in patients on chronic Sandostatin® (octreotide acetate) therapy.

Cardiac

In acromegalics, sinus bradycardia (< 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias developed in 9% of patients during Sandostatin therapy.

Gastrointestinal

Diarrhea, loose stools, nausea and abdominal discomfort were each seen in 34%-61% of acromegalic patients in U.S. studies although only 2.6% of the patients discontinued therapy due to these symptoms. These symptoms were seen in 5%-10% of patients with other disorders.

The frequency of these symptoms was not dose-related, but diarrhea and abdominal discomfort generally resolved more quickly in patients treated with 300 mcg/day than in those treated with 750 mcg/day. Vomiting, flatulence, abnormal stools, abdominal distention, and constipation were each seen in less than 10% of patients.

In rare instances, gastrointestinal side effects may resemble acute intestinal obstruction, with progressive abdominal distension, severe epigastric pain, abdominal tenderness and guarding.

Hypo/Hyperglycemia

Hypoglycemia and hyperglycemia occurred in 3% and 16% of acromegalic patients, respectively, but only in about 1.5% of other patients. Symptoms of hypoglycemia were noted in approximately 2% of patients.

Hypothyroidism

In acromegalics, biochemical hypothyroidism alone occurred in 12% while goiter occurred in 6% during Sandostatin therapy. In patients without acromegaly, hypothyroidism has only been reported in several isolated patients and goiter has not been reported.

Other Adverse Events

Pain on injection was reported in 7.7%, headache in 6% and dizziness in 5%. Pancreatitis was also observed.

Other Adverse Events 1%-4%

Other events (relationship to drug not established), each observed in 1%-4% of patients, included fatigue, weakness, pruritus, joint pain, backache, urinary tract infection, cold symptoms, flu symptoms, injection site hematoma, bruise, edema, flushing, blurred vision, pollakiuria, fat malabsorption, hair loss, visual disturbance and depression.

Other Adverse Events < 1%

Events reported in less than 1% of patients and for which relationship to drug is not established are listed: Gastrointestinal: hepatitis, jaundice, increase in liver enzymes, GI bleeding, hemorrhoids, appendicitis, gastric/peptic ulcer, gallbladder polyp;

Integumentary: rash, cellulitis, petechiae, urticaria, basal cell carcinoma;

Musculoskeletal: arthritis, joint effusion, muscle pain, Raynaud's phenomenon;

Cardiovascular: chest pain, shortness of breath, thrombophlebitis, ischemia, congestive heart failure, hypertension, hypertensive reaction, palpitations, orthostatic BP decrease, tachycardia;

CNS: anxiety, libido decrease, syncope, tremor, seizure, vertigo, Bell's Palsy, paranoia, pituitary apoplexy, increased intraocular pressure, amnesia, hearing loss, neuritis;

Respiratory: pneumonia, pulmonary nodule, status asthmaticus;

Endocrine: galactorrhea, hypoadrenalism, diabetes insipidus, gynecomastia, amenorrhea, polymenorrhea, oligomenorrhea, vaginitis;

Urogenital: nephrolithiasis, hematuria;

Hematologic: anemia, iron deficiency, epistaxis;

Miscellaneous: otitis, allergic reaction, increased CK, weight loss.

Evaluation of 20 patients treated for at least 6 months has failed to demonstrate titers of antibodies exceeding background levels. However, antibody titers to Sandostatin were subsequently reported in three patients and resulted in prolonged duration of drug action in two patients. Anaphylactoid reactions, including anaphylactic shock, have been reported in several patients receiving Sandostatin.

Postmarketing Experience

The following adverse reactions have been identified during the postapproval use of Sandostatin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatobiliary: cholelithiasis, cholecystitis, cholangitis and pancreatitis, which have sometimes required cholecystectomy

Gastrointestinal: intestinal obstruction

Hematologic: thrombocytopenia

Sandostatin has been associated with alterations in nutrient absorption, so it may have an effect on absorption of orally administered drugs. Concomitant administration of Sandostatin with cyclosporine may decrease blood levels of cyclosporine and result in transplant rejection.

Patients receiving insulin, oral hypoglycemic agents, beta blockers, calcium channel blockers, or agents to control fluid and electrolyte balance, may require dose adjustments of these therapeutic agents.

Concomitant administration of octreotide and bromocriptine increases the availability of bromocriptine. Limited published data indicate that somatostatin analogs might decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of growth hormones.

Since it cannot be excluded that octreotide may have this effect, other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (e.g., quinidine, terfenadine) should therefore be used with caution.

Drug/Laboratory Test Interactions

No known interference exists with clinical laboratory tests, including amine or peptide determinations.

Drug Abuse And Dependence

There is no indication that Sandostatin has potential for drug abuse or dependence. Sandostatin levels in the central nervous system are negligible, even after doses up to 30,000 mcg.