FDA label b41326b8-8138-4e6c-b294-ae005aa697b9

WARNINGS Cholelithiasis and Complications of Cholelithiasis Single doses of Octreotide Acetate Injection have been shown to inhibit gallbladder contractility and decrease bile secretion in normal volunteers. In clinical trials (primarily patients with acromegaly or psoriasis), the incidence of biliary tract abnormalities was 63% (27% gallstones, 24% sludge without stones, 12% biliary duct dilatation). The incidence of stones or sludge in patients who received octreotide acetate for 12 months or longer was 52%. Less than 2% of patients treated with octreotide acetate for 1 month or less developed gallstones. The incidence of gallstones did not appear related to age, sex, or dose. Like patients without gallbladder abnormalities, the majority of patients developing gallbladder abnormalities on ultrasound had gastrointestinal symptoms. The symptoms were not specific for gallbladder disease. A few patients developed acute cholecystitis, ascending cholangitis, biliary obstruction, cholestatic hepatitis, or pancreatitis during octreotide acetate therapy or following its withdrawal. One patient developed ascending cholangitis during octreotide acetate therapy and died. There have been postmarketing reports of cholelithiasis (gallstones) resulting in complications requiring cholecystectomy. If complications of cholelithiasis are suspected, discontinue octreotide acetate and treat appropriately. Complete Atrioventricular Block Patients who receive Octreotide Acetate Injection intravenously may be at increased risk for higher degree atrioventricular blocks. In postmarketing reports, complete atrioventricular block was reported in patients receiving intravenous Octreotide Acetate Injection during surgical procedures. In majority of patients, Octreotide Acetate Injection was given at higher than recommended doses and/or as a continuous intravenous infusion. The safety of continuous intravenous infusion has not been established in patients receiving Octreotide Acetate Injection for the approved indications. Consider cardiac monitoring in patients receiving Octreotide Acetate Injection intravenously.

ADVERSE REACTIONS Gallbladder Abnormalities Gallbladder abnormalities, especially stones and/or biliary sludge, frequently develop in patients on chronic Octreotide Acetate Injection therapy (see WARNINGS ). Cardiac In acromegalics, sinus bradycardia (< 50 bpm) developed in 25%; conduction abnormalities occurred in 10% and arrhythmias developed in 9% of patients during octreotide acetate therapy (see PRECAUTIONS, General ). Gastrointestinal Diarrhea, loose stools, nausea, and abdominal discomfort were each seen in 34% to 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% to 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 octreotide acetate therapy (see PRECAUTIONS, General ). 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 (see WARNINGS and PRECAUTIONS ). Other Adverse Events 1% to 4% Other events (relationship to drug not established), each observed in 1% to 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 Less Than 1% Events reported in less than 1% of patients and for which relationship to Octreotide Acetate Injection is not established are listed: Gastrointestinal (GI): 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 octreotide acetate were subsequently reported in 3 patients and resulted in prolonged duration of drug action in 2 patients. Anaphylactoid reactions, including anaphylactic shock, have been reported in several patients receiving octreotide acetate. Postmarketing Experience The following adverse reactions have been identified during the postapproval use of octreotide acetate. 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 To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .