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  • CLASSES

    Antigrowth Hormones
    Somatostatin and analogs

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral synthetic analog of somatostatin
    Used for acromegaly, symptoms associated with vasoactive intestinal peptide tumors (VIPomas; watery diarrhea), metastatic carcinoid tumors, AIDS-associated diarrhea, esophageal varices, and other indications
    Longer half-life, greater selectivity, and a lower incidence of rebound hypersecretion than somatostatin

    COMMON BRAND NAMES

    Sandostatin, Sandostatin LAR

    HOW SUPPLIED

    Octreotide/Octreotide Acetate/Sandostatin Intravenous Inj Sol: 1mL, 50mcg, 100mcg, 200mcg, 500mcg, 1000mcg
    Octreotide/Octreotide Acetate/Sandostatin Subcutaneous Inj Sol: 1mL, 50mcg, 100mcg, 200mcg, 500mcg, 1000mcg
    Sandostatin LAR Intramuscular Inj Pwd F/Susp: 10mg, 20mg, 30mg

    DOSAGE & INDICATIONS

    For the treatment of acromegaly.
    NOTE: Octreotide has been designated an orphan drug by the FDA for this indication.
    Subcutaneous dosage (solution for injection)
    Adults

    Initiate therapy at 50 mcg subcutaneously 3 times daily. The most common effective dose is 100 to 200 mcg subcutaneously 3 times daily; some patients require doses up to 500 mcg subcutaneously 3 times daily; no added benefit attributed to dosages of 1500 mcg/day. IGF-1 levels every 2 weeks can be used to guide titration or, alternatively, multiple growth hormone levels at 0—8 hours after octreotide injection may permit more rapid titration of the dose. If an increase in dose fails to provide any additional benefit, reduce the dose. In patients who have received irradiation, octreotide should be withdrawn yearly for approximately 1 month to assess disease activity. If growth hormone or IGF-1 levels increase and signs and symptoms recur, octreotide therapy may be restarted.

    Intramuscular dosage (injectable depot suspension)
    Adults

    Patients responding to subcutaneous octreotide may initiate with 20 mg depot injection suspension IM every 4 weeks for 3 months. After 3 months may adjust as follows: for growth hormone (GH) serum levels of 2.5 ng/mL or less, IGF-1 normal and clinical symptoms controlled, continue same dosage; for GH serum levels greater than 2.5 ng/mL, IGF-1 elevated and/or clinical symptoms uncontrolled, increase dosage to 30 mg IM every 4 weeks; for GH of 1 ng/mL or less, IGF-1 normal and clinical symptoms controlled, decrease dose to 10 mg IM every 4 weeks. In patients whose symptoms and lab parameters are not controlled at 30 mg/month, may increase to 40 mg IM every 4 weeks. Max: 40 mg IM every 4 weeks. Dosing intervals longer than 4 weeks are not recommended. On a yearly basis, patients who have received pituitary irradiation, should have the depot octreotide therapy held for 8 weeks to assess disease activity. If GH or IGF-1 levels increase and signs and symptoms recur, octreotide therapy should be restarted.

    For the treatment of symptoms associated with carcinoid tumors, specifically, diarrhea and cutaneous flushing.
    NOTE: Octreotide has been designated an orphan drug by the FDA for this indication. 
    Subcutaneous dosage (solution for injection)
    Adults

    100 mcg to 600 mcg/day subcutaneously, given in 2 to 4 divided doses, for the first 2 weeks. The mean dosage is 300 mcg/day; some patients may require doses up to 1500 mcg/day.

    Intramuscular dosage (injectable depot suspension)
    Adults

    In adults with a response to subcutaneous use of octreotide, give 20 mg IM depot injection intragluteally every 4 weeks for 2 months. Patients should continue the previous subcutaneous dosage for up to 2 weeks after starting the IM injections (some patients may require up to 4 weeks). Patients who do not continue the subcutaneous injections during this time may have an exacerbation of their symptoms. After 2 months, if the patient did not respond, may increase to 30 mg IM every 4 weeks. For maintenance, give a trial of 10 mg IM every 4 weeks if the patient responded to the initial dose; if symptoms increase, then increase the dose. Max: 30 mg IM every 4 weeks. Dosing intervals greater than 4 weeks are not recommended. Some patients experience periodic exacerbations that may require temporary management with subcutaneous octreotide, which may be halted once symptoms resolve.

    For the treatment of symptoms associated with vasoactive intestinal peptide tumors (e.g., VIPoma) (i.e., to reduce plasma concentrations of vasoactive intestinal peptide).
    NOTE: Octreotide has been designated an orphan drug by the FDA for this indication.
    Subcutaneous dosage (solution for injection)
    Adults

    200 mcg to 300 mcg/day subcutaneously, given in 2 to 4 divided doses, for the first 2 weeks; then titrate. Dosage range: 150 to 750 mcg/day. Maintenance doses must be individualized. Doses above 450 mcg/day are usually not required.

    Intramuscular dosage (injectable depot suspension)
    Adults who have responded to and tolerate SC octreotide

    In adults with a response to subcutaneous use of octreotide, give 20 mg IM depot injection intragluteally every 4 weeks for 2 months. Patients should continue the previous subcutaneous dosage for up to 2 weeks after starting the IM injections (some patients may require up to 4 weeks). Patients who do not continue the subcutaneous injections during this time may have an exacerbation of their symptoms. After 2 months, if the patient did not respond, may increase to 30 mg IM every 4 weeks. For maintenance, give a trial of 10 mg IM every 4 weeks if the patient responded to the initial dose; if symptoms increase, then increase the dose. Max: 30 mg IM every 4 weeks. Dosing intervals greater than 4 weeks are not recommended. Some patients experience periodic exacerbations that may require temporary management with subcutaneous octreotide, which may be halted once symptoms resolve.

    For the management of intractable diarrhea† or ileostomy-associated diarrhea†.
    Intravenous dosage
    Adults

    Uncontrolled trials of both IV and subcutaneous octreotide have shown benefit in patients with ileostomy-associated diarrhea; however, in some cases the benefits have been offset by an increase in diarrhea due to fat malabsorption. Five patients who received octreotide 25 mcg/hour by continuous IV infusion showed a significant reduction in ileostomy output, an increase in water excretion, and a prolonged small-bowel transit time. Two of these patients were subsequently continued on subcutaneous octreotide.

    Neonates, Infants, Children, and Adolescents

    2 to 10 mcg/kg/day IV given in divided doses twice daily is the most commonly reported dosage range; begin at the lower end of the dosage range and titrate to clinical response. Doses up to 18 mcg/kg/day have been reported in patients with intractable diarrhea.

    Subcutaneous dosage
    Adults

    Varying doses reported. Two patients with ileostomy-associated diarrhea were given octreotide 50 mcg subcutaneously twice daily after initially receiving IV octreotide infusion. Octreotide improved symptoms and decreased the need for intravenous fluids. No benefit was observed with doses in excess of 50 mcg subcutaneously every 8 hours. In another uncontrolled trial, 12 patients given octreotide 100 mcg subcutaneously 3 times daily for 5 days showed a reduction in ileostomy output.

    Neonates, Infants, Children, and Adolescents

    2 to 10 mcg/kg/day subcutaneously given in divided doses twice daily is the most commonly reported dosage range; begin at the lower end of the dosage range and titrate to clinical response. Doses up to 18 mcg/kg/day have been reported in patients with intractable diarrhea.

    For the management of chemotherapy-induced diarrhea† in pediatric patients.
    Intermittent Intravenous or Subcutaneous dosage
    Neonates, Infants, Children, and Adolescents

    2 to 10 mcg/kg/day given in divided doses IV or subcutaneously twice daily is the most commonly reported dosage range; begin at the lower end of the dosage range and titrate to clinical response. Doses up to 18 mcg/kg/day have been reported in patients with intractable diarrhea.

    Continuous Intravenous Infusion dosage
    Children and Adolescents

    1 mcg/kg/hour as a continuous IV infusion has been reported as efficacious in a pediatric case report of diarrhea secondary to graft vs. host disease.

    For the control of diarrhea secondary to AIDS-associated enteropathy†.
    Subcutaneous dosage (solution for injection)
    Adults

    Uncontrolled studies indicate responsiveness with an initial dose of 50 mcg subcutaneously every 8 hours as needed, and then titrated to effectiveness, especially if no infectious etiology is present. Effective dose range reported for most patients is 100 to 250 mcg subcutaneously every 8 hours. Doses up to 500 mcg subcutaneously every 8 hours have been reported. Twenty-one (41%) patients in one study responded and in a second study (n = 11), 5 patients (45%) responded favorably to treatment. A third study involved 29 patients with AIDS-associated diarrhea. Twenty-one patients had positive stool cultures for Cryptosporidium species and 1 for Isospora belli. Seven patients had no identifiable infectious agent on stool culture. Of the 25 evaluable patients, 10 (40%) had a complete response to octreotide (defined as a reduction in the number of bowel movements to 2 bowel movements/day or less). Nine patients had a partial response (defined as a 50% reduction in stool output or an increase in stool consistency). All 3 studies suggest that response is more likely in patients with negative stool cultures than in those whose diarrhea had an infectious etiology.

    For the treatment of dumping syndrome†.
    Subcutaneous dosage (solution for injection)
    Adults

    Single doses of 50 to 100 mcg subcutaneously were studied in placebo-controlled crossover trials in meal-stimulated dumping syndrome. Octreotide reduced symptoms in patients with early dumping syndrome including a significantly decreased pulse rate. Patients with late dumping syndrome showed an inhibition of insulin secretion and did not experience hypoglycemia. In patients with severe postvagotomy or postgastrectomy symptoms, octreotide 50 mcg subcutaneously twice daily showed benefit in 6 of 14 patients after 3 months.

    For the treatment of short bowel syndrome†.
    Subcutaneous or Intravenous dosage (solution for injection)
    Adults

    In a randomized, double-blind, crossover study involving 6 patients, 2 octreotide regimens were used: 25 mcg/hour continuous IV infusion for 2 days or 50 mcg subcutaneously every 12 hours for 2 days. Both regimens were significantly more effective than placebo, however, treatment did not eliminate the need for IV fluids. In 3 of 4 patients who received octreotide for 4 to 6 months, reductions in fecal sodium and water loss were maintained. In an open-label, uncontrolled study, 6 patients with short bowel syndrome received octreotide 50 mcg subcutaneously or IV every 12 hours. A 73% reduction in diarrhea was reported for 5 of 6 patients. Dosages greater than 50 mcg twice daily did not provide any added benefit.

    For the treatment of enterocutaneous fistula†.
    Subcutaneous dosage (solution for injection)
    Adults

    Doses have ranged from 75 mcg to 100 mcg subcutaneously every 8 hours. The efficacy of octreotide in enterocutaneous fistulas was examined in a randomized, double-blind, placebo-controlled study involving 14 patients who had not responded to 7 days of total parenteral nutrition, cimetidine, and nasogastric suction. Patients received octreotide 225 to 300 mcg/day subcutaneously in divided doses for 2 days before being crossed over to placebo. All patients had a reduction in fistula output while on octreotide. Octreotide was continued after study completion. Fistulas closed in 11 (78%) patients within 2 to 10 days (mean: 4 to 5 days). Fistulas failed to close in 3 patients with high-output fistulas. Similar results were obtained in an open-label study of octreotide 100 mcg subcutaneously every 8 hours.

    For reducing output from a pancreatic fistula†.
    Subcutaneous dosage
    Adults

    In an uncontrolled study, octreotide 100 mcg subcutaneously every 8 hours was administered to 8 patients with high-output pancreatic fistulas. Resolution occurred at a mean of 23 days in 7 patients. According to this study, patients with fistulas secondary to obstructed ductal drainage or an infected fistular tract are unlikely to respond to octreotide therapy.

    For adjunct therapy to endoscopic variceal ligation in the treatment of upper GI bleeding† or variceal bleeding† in patients with esophageal varices†.
    Intravenous dosage (solution for injection)
    Adults

    50 or 100 mcg IV bolus followed by 25 or 50 mcg/hour continuous IV infusion for 3 to 5 days. Clinical practice guidelines support the adjunctive use of octreotide in combination with endoscopic intervention for patients with bleeding varices. Octreotide therapy should be initiated as soon as variceal hemorrhage is suspected and continued for 3 to 5 days after diagnosis is confirmed.

    Infants, Children, and Adolescents

    1 to 2 mcg/kg IV bolus over 5 minutes, then 1 to 2 mcg/kg/hour continuous IV infusion. Titrate infusion to clinical response. After 24 hours of no active bleeding, taper infusion rate by 50% every 12 hours; discontinue infusion when the rate is 25% of the original dose. In a review of pediatric patients with acute GI bleeding, median duration of therapy for those with portal hypertension (n = 21) was 50 hours (range 19 hours to 7 days); for patients without portal hypertension (n = 12), median duration was 43 hours (range 3 hours to 36 days).

    For the treatment of hyperthyroidism† secondary to thyrotropinoma†.
    Subcutaneous dosage
    Adults

    Initially, 50 to 100 mcg subcutaneously 2 to 3 times per day. Titrate to response. Max: 500 mcg subcutaneously every 8 hours. In one retrospective study, 52 cases of TSH-secreting adenomas treated with octreotide were reviewed. TSH levels were decreased in 50 patients and thyroid hormone levels were reduced in all patients. Thyroid hormone levels returned to normal levels in 73% of patients.

    For the treatment of hypoglycemia in patients with hyperinsulinism, including patients with benign or malignant insulinoma†.
    Subcutaneous dosage (solution for injection)
    Adults

    The optimal dosage has not been established. In small numbers of patients with insulinoma, dosages of 100 to 450 mcg/day subcutaneously given in 2 to 3 divided doses have been used to normalize blood glucose. Limited data indicate dosages of 300 to 1500 mcg/day subcutaneous continuous infusion may also normalize fasting blood glucose.

    For the treatment of neurogenic orthostatic hypotension†.
    Subcutaneous dosage (solution for injection)
    Adults

    Optimal dose not established. A usual starting dose is 12.5 mcg to 25 mcg subcutaneously 3 times per day, then titrated to effect. Usually reserved for patients not responsive to standard therapies due to limited data. One study has used 100 mcg subcutaneously as a single dose acutely. In an uncontrolled study, 28 patients with various types of autonomic neuropathy received both low (0.2 to 0.4 mcg/kg subcutaneously) and high (up to 1.6 mcg/kg subcutaneously) dose octreotide. At low doses, an average increase in semirecumbent blood pressure of 15 to 20 mmHg was observed in patients with progressive autonomic failure, multiple organ system atrophy, and diabetic autonomic neuropathy. High doses resulted in elevation in blood pressures for up to 50 minutes while walking in 4 of 6 patients with progressive autonomic failure and 1 of 6 patients with multiple organ system atrophy.

    For the treatment of hepatorenal syndrome† in combination with midodrine and albumin.
    Subcutaneous dosage (solution for injection)
    Adults

    Octreotide 100 to 200 mcg subcutaneously 3 times daily in combination with midodrine (range: 5 to 15 mg orally three times daily) and albumin at varying doses (e.g., 1 gram/kg/day or less IV) has been reported to improve short-term survival and renal function compared to conventional supportive therapy and may allow a bridge to transplantation. Titrate medications according to clinical response. Two trials titrated doses targeting a mean arterial pressure (MAP) increase of 15 mm Hg or more over baseline ; a third trial titrated doses to response and not to exceed a systolic blood pressure (SBP) of 140 mmHg. Octreotide is not effective as monotherapy. Therapy with octreotide, midodrine and albumin appears inferior to the use of terlipressin with albumin.

    For the treatment of acute cluster headache†.
    Subcutaneous dosage
    Adults

    100 mcg subcutaneously once.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Dependent on indication for therapy, route of administration, and patient response.

    Geriatric

    Dependent on indication for therapy, route of administration, and patient response.

    Adolescents

    Dependent on indication for therapy, route of administration, and patient response. For hypothalamic obesity, 15 mcg/kg/day subcutaneously.

    Children

    Dependent on indication for therapy, route of administration, and patient response. For chylothorax, 10 mcg/kg/hour IV continuous infusion is the maximum recommended rate; for congenital hyperinsulinemia, 40 mcg/kg/day subcutaneously or IV; for hypothalamic obesity, 15 mcg/kg/day subcutaneously.

    Infants

    Dependent on indication for therapy, route of administration, and patient response. For chylothorax, 10 mcg/kg/hour IV continuous infusion is the maximum recommended rate; for congenital hyperinsulinemia, 40 mcg/kg/day subcutaneously or IV.

    Neonates

    Dependent on indication for therapy, route of administration, and patient response. For chylothorax, 10 mcg/kg/hour IV continuous infusion is the maximum recommended rate; for congenital hyperinsulinemia, 40 mcg/kg/day subcutaneously or IV.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Cirrhosis and fatty liver disease prolong the half-life and reduce the clearance of octreotide. Specific guidelines for dosage adjustments in hepatic impairment are not available for the immediate release SC or IV injection. The initial dose of the depot IM suspension should be decreased by 50% in adult patients (e.g., 10 mg IM) with cirrhosis; the dose should be titrated based on clinical response. Once at a higher dose, patient should be maintained or dose-adjusted based on response and tolerability as in any noncirrhotic patient.

    Renal Impairment

    In adult patients with mild, moderate, or severe renal impairment (non-dialysis patients) there is no need to adjust the initial dose of octreotide; the maintenance dose should be adjusted based on clinical response and tolerability as in nonrenal patients.
     
    Intermittent Hemodialysis
    Clearance is decreased by 50% in adult patients with severe renal impairment requiring dialysis. Specific guidelines for dosage adjustments in severe renal impairment or dialysis are not available for the immediate release SC or IV formulation. The initial dose of the depot IM injection suspension should be decreased by 50% in adult patients (e.g., 10 mg IM); titrate and dose-adjust based on clinical response and tolerability as in nonrenal patients.

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
     
    Octreotide Injection Solution (e.g., Sandostatin)
    For intravenous (IV) or subcutaneous administration only.
    Storage: Unopened injection solution is stored at refrigerated temperatures between 2 and 8 degrees C (36 and 46 degrees F) in the outer carton to protect from light. Unopened ampules and vials are stable for 14 days at room temperature if protected from light. Discard any unused portion of an ampul once opened. Discard multiple-dose vials 14 days after initial use.
     
    Octreotide Depot Injection Suspension (Sandostatin LAR depot)
    For intramuscular (IM) injection once monthly into the gluteal region only. Do NOT administer by any other route.
    Storage: Unopened Sandostain LAR kits are stored at refrigerated temperature between 2 and 8 degrees C (36 and 46 degrees F), in the outer carton to protect from light, until the time of use.
    Questions about product acquisition or product preparation and/or administration can be answered by calling the PEAK (Pituitary Education, Access, and Knowledge) assistance line at 1-877-503-3377 between the hours of 8:00 AM and 8:00 PM eastern standard time (EST). Healthcare providers may also contact the Sandostatin Support Hotline at 1-800-282-7630.

    Intravenous Administration

    Octreotide Injection Solution (e.g., Sandostatin)
    May administer intravenously (IV) as either an injection or as an infusion.
    Octreotide injection solution can be allowed to reach room temperature prior to administration. Do not warm artificially.
     
    IV Push Injection
    In emergency situations, octreotide may be administered undiluted by intermittent direct IV injection. Give IV slowly over 3 minutes.
     
    Intermittent IV Infusion
    Dilute in 50 mL to 200 mL of 0.9% Sodium Chloride or 5% Dextrose injection; infuse IV over 15 to 30 minutes.
    Once diluted, the infusion solution is stable for 24 hours.
     
    Continuous IV Infusion
    Dilute in 50 mL to 200 mL of 0.9% Sodium Chloride or 5% Dextrose injection.
    Administer the continuous infusion at the ordered dose rate using a rate-controlled infusion device.
    Once diluted, the IV infusion is stable for 24 hours.

    Intramuscular Administration

    Octreotide Depot Injection Suspension (Sandostatin LAR Depot) ONLY
    For intramuscular (IM) administration as a once monthly (every 4 weeks) injection. Do NOT give by any other route.
    An instruction booklet for preparation of the depot IM drug suspension is provided in each kit. Use the provided diluent only.
    Preparation:
    Drug product kit should be removed from the refrigerator and should stand at room temperature for a minimum of 30 minutes (not to exceed 24 hours) prior to preparation of the suspension. If necessary, the kit may be re-refrigerated.
    Remove plastic cap from vial containing Sandostatin LAR powder and clean the vial stopper with an alcohol swab.
    Remove the lid film of the vial adapter packaging and position the vial adapter on top of the vial and push it down until it snaps in place, confirmed by an audible "click". Lift the packaging off the vial adapter.
    Remove cap from syringe prefilled with diluent solution and screw syringe onto vial adapter. 
    Slowly push plunger all the way down to transfer all of the diluent solution into the vial. Do not disturb the vial while the diluent saturates the powder. After 2 to 5 minutes, without inverting the vial, check the sides and bottom of vial for dry spots. The powder must be fully saturated before withdrawing from the vial.
    Once the powder is completely saturated, press plunger all the way back into the syringe. Keep plunger pressed and shake vial moderately in a horizontal direction for approximately 30 seconds to form a uniform milky suspension.
    Repeat shaking for another 30 seconds if powder is not completely suspended.
    Prepare Syringe to Administer Depot Injection:
    Turn the syringe and vial upside down and slowly pull the plunger out to draw entire contents from vial into the syringe.
    Unscrew syringe from the vial adapter.
    Peel off outer syringe label.
    Just prior to injection, screw safety injection needle onto syringe, pull protective cover straight off needle, and gently shake syringe to maintain a uniform suspension.
    Gently tap syringe to remove any visible bubbles and eliminate air from syringe. Ensure that the powder is completely suspended at the time of injection.
    Administer immediately after preparation. Failure to inject immediately after suspension preparation may cause the product to become solid. If the product 'clumps' or flocculates, it is not usable. The preparation process will need to begin again with a new kit.
    Injection Administration:
    Must be given only by deep intragluteal IM injection. NEVER give intravenously.
    Inject immediately after product preparation.
    Prepare the injection site with an alcohol wipe.
    Insert the needle fully into the left or right gluteus at a 90 degree angle to the skin.
    At the next monthly injection, rotate the gluteal IM injection site.

    Subcutaneous Administration

    Octreotide Injection Solution (e.g., Sandostatin)
    Administer subcutaneously undiluted, unless the injection dose volume cannot be accurately administered without further dilution with 0.9% Sodium Chloride for injection.
    To minimize pain, use smallest injection volume that will deliver the desired dose.
    May allow the injection to reach room temperature before administration. However, do not artificially warm the injection.

    STORAGE

    Sandostatin:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Product is stable for up to 14 days at temperatures between 70 and 86 degrees F if protected from light
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    Sandostatin LAR:
    - Protect from light
    - Reconstituted product should be used immediately. Discard unused portion
    - Refrigerated product should reach room temperature before administration
    - Store between 36 to 46 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Octreotide has been shown to alter the absorption of dietary fats in some patients.

    Biliary obstruction, biliary tract disease, cholangitis, cholelithiasis, gallbladder disease

    Use octreotide with caution in patients with biliary tract disease or gallbladder disease. Octreotide decreases bile secretion, modifies bile composition, and decreases gallbladder motility. Patients may be at risk for developing acute cholecystitis, ascending cholangitis, biliary obstruction, and cholestatic hepatitis during or shortly after octreotide therapy. The incidence of gallstones (cholelithiasis) does not appear to be related to age, sex, or dose but may be influenced by duration of octreotide therapy; a longer duration of octreotide use may increase the risk of cholelithiasis. In adult clinical trials of patients with acromegaly and psoriasis, less than 2% of patients treated with octreotide for <= 1 month developed gallstones; however, those on therapy >= 12 months had a 52% incidence rate of developing gallstones or biliary sludge. Gallstones are typically small and asymptomatic; in general, periodic ultrasounds are not recommended.

    Pancreatitis

    Although octreotide has been studied in the adjunctive treatment of acute pancreatitis, results of these studies have been controversial. Octreotide is known to increase the frequency of sphincter of Oddi contractions which could impair the flow of bile and pancreatic juices into the duodenum, possibly leading to pancreatic complications. Several cases of new onset pancreatitis have been reported in patients receiving octreotide therapy.

    Hepatic disease

    Use octreotide with caution in patients with hepatic disease. Adult patients with cirrhosis or fatty liver disease have a prolonged half-life and decreased clearance when compared to healthy subjects. Initial dosage adjustments may be necessary.

    Dialysis, renal failure

    Use octreotide with caution in patients with severe renal failure requiring dialysis. Drug clearance is reduced by approximately 50% in adult patients with severe renal failure requiring dialysis. Dosage adjustments may be necessary.

    Diabetes mellitus, gastroparesis, hyperglycemia, hypoglycemia

    Use octreotide with caution in patients with pre-existing diabetes mellitus or in patients with conditions resulting in blood glucose alterations. Octreotide may cause hypoglycemia or hyperglycemia by altering the balance of insulin, glucagon, and growth hormone in the body. Though glycemic effects are usually mild, overt diabetes mellitus and the need to alter dosages of insulin or other hypoglycemic agents may occur. Insulin requirements may be reduced in patients with type 1 diabetes mellitus. Conversely, insulin levels may decrease and hyperglycemia may occur in non-diabetics and in patients with type 2 diabetes with partially intact insulin reserves. Monitor blood glucose, glucose tolerance, and antidiabetic treatment periodically. In addition, octreotide may worsen symptoms of gastroparesis by reducing gut motility; use with caution in patients with diabetic gastroparesis.

    Goiter, hypothyroidism

    Octreotide suppresses the secretion of thyroid stimulating hormone which may result in hypothyroidism or goiter. Baseline and periodic assessment of thyroid function (TSH, total, and/or free T4) is recommended during chronic therapy.

    Fat malabsorption, vitamin B12 deficiency

    Vitamin B12 deficiency may occur in patients receiving octreotide; chronic use has been associated with an abnormal Schilling test. In addition, octreotide may cause dietary fat malabsorption. Monitor vitamin B12 levels during chronic therapy. Patients experiencing steatorrhea should have nutritional assessments and monitoring of weight as indicated.

    Pregnancy

    There are no adequate and well-controlled studies of octreotide use during human pregnancy. It is known to cross the human placenta and has been measured in the newborn. Available human pregnancy data are limited. Most women who have taken octreotide during pregnancy have taken it during the first trimester; doses ranged from 200 to 300 mcg/day subcutaneously (injection solution) or 20 to 30 mg/month IM (long-acting depot suspension formulation). In those women who continued it throughout pregnancy and had a known outcome, congenital abnormalities were not reported. The few cases describing octreotide use during some portion of pregnancy resulted in normal outcomes to the fetus. Reproduction studies have been performed in rats and rabbits at doses up to 16-times the highest recommended human dose and have revealed no evidence of harm to the fetus due to octreotide. The drug should only be used during pregnancy if clearly needed.

    Breast-feeding

    Use octreotide with caution in women who are breast-feeding, particularly if the infant is under 2 months of age, due to the minimal data available. It is not known if octreotide is excreted in breast milk. Because the drug is poorly absorbed following oral administration, the risk to the nursing infant appears to be minimal. Documentation of octreotide use during breast-feeding is lacking; however, there is a published report of a woman receiving octreotide for acromegaly who breast-fed for 4 months with no adverse effects or problems with feeding in the infant.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, electrolyte imbalance, females, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, malnutrition, myocardial infarction, QT prolongation, thyroid disease

    Use octreotide with caution in patients with cardiac disease and heart failure. Octreotide has been associated with sinus bradycardia, cardiac arrhythmias, QT prolongation, and conduction abnormalities in adult acromegalic and carcinoid syndrome patients. Other ECG changes observed included QT prolongation, axis shifts, early repolarization, low voltage, R/S transition, and early R wave progression. These ECG changes are not uncommon in acromegalic patients. Initiation of octreotide therapy resulted in worsening of congestive heart failure (CHF) in an adult acromegalic patient with severe CHF; causality was established with improvement upon discontinuation and a positive rechallenge. Dose adjustments in drugs such as beta-blockers or other cardiovascular medications that have bradycardia effects may be necessary. Use octreotide with caution in patients receiving other drugs that cause QT prolongation or other ECG abnormalities. Avoid use in patients with known or suspected congenital long QT syndrome. Use octreotide with caution in patients with other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalance. Females, elderly patients, patients with diabetes, thyroid disease, malnutrition, alcoholism, or hepatic impairment may also be at increased risk for QT prolongation.

    Growth inhibition, infants, necrotizing enterocolitis, neonates, premature neonates

    Growth inhibition has been reported in some pediatric patients treated with octreotide for more than 1 year, and use of the drug in pediatric patients requires close monitoring of clinical parameters related to the condition being treated as well as weight gain and growth with chronic use. Neonates and infants receiving octreotide may be at increased risk for developing necrotizing enterocolitis (NEC). Octreotide increases splanchnic blood vascular resistance and reduces gut blood flow. Though the pathophysiology of NEC is multifactorial and not completely understood, there have been several care reports of NEC in term neonates associated with octreotide use. Infants receiving octreotide should be closely monitored for NEC, particularly if they have other risk factors (e.g., premature neonates, congenital heart disease).

    Geriatric

    Clinical studies of octreotide did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Reported clinical experience has not identified differences in responses between the geriatric patients and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the lower end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 19.0-25.0
    visual impairment / Early / 1.0-4.0
    cholecystitis / Delayed / 0-1.0
    cranial nerve palsies / Delayed / 0-1.0
    seizures / Delayed / 0-1.0
    peptic ulcer / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    enterocolitis / Delayed / Incidence not known
    ileus / Delayed / Incidence not known
    GI obstruction / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    biliary obstruction / Delayed / Incidence not known
    cardiac arrest / Early / Incidence not known
    pulmonary hypertension / Delayed / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    heart failure / Delayed / Incidence not known
    pituitary apoplexy / Early / Incidence not known
    diabetes insipidus / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    suicidal ideation / Delayed / Incidence not known
    intracranial bleeding / Delayed / Incidence not known
    retinal thrombosis / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    thrombosis / Delayed / Incidence not known
    pleural effusion / Delayed / Incidence not known
    pneumothorax / Early / Incidence not known
    pulmonary embolism / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    ocular hypertension / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known

    Moderate

    hyperglycemia / Delayed / 15.0-27.0
    antibody formation / Delayed / 0-25.0
    constipation / Delayed / 0-18.8
    hypertension / Early / 0-12.6
    goiter / Delayed / 2.0-8.0
    hematoma / Early / 1.0-4.0
    hypoglycemia / Early / 1.5-4.0
    blurred vision / Early / 1.0-4.0
    edema / Delayed / 1.0-4.0
    cholangitis / Delayed / 0-1.0
    sinus tachycardia / Rapid / 0-1.0
    chest pain (unspecified) / Early / 0-1.0
    palpitations / Early / 0-1.0
    neuritis / Delayed / 0-1.0
    depression / Delayed / 0-1.0
    anemia / Delayed / 0-1.0
    hematuria / Delayed / 0-1.0
    nephrolithiasis / Delayed / 0-1.0
    cholelithiasis / Delayed / 10.0
    hepatitis / Delayed / Incidence not known
    steatosis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    hemorrhoids / Delayed / Incidence not known
    ascites / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    orthostatic hypotension / Delayed / Incidence not known
    ST-T wave changes / Rapid / Incidence not known
    phlebitis / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known
    vitamin B12 deficiency / Delayed / Incidence not known
    galactorrhea / Delayed / Incidence not known
    vaginitis / Delayed / Incidence not known
    hypothyroidism / Delayed / Incidence not known
    growth inhibition / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    migraine / Early / Incidence not known
    aphasia / Delayed / Incidence not known
    amnesia / Delayed / Incidence not known
    paresis / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    scotomata / Delayed / Incidence not known

    Mild

    nausea / Early / 5.0-61.0
    diarrhea / Early / 5.0-61.0
    abdominal pain / Early / 5.0-61.0
    headache / Early / 6.0-30.0
    back pain / Delayed / 0-27.3
    flatulence / Early / 0-25.7
    dizziness / Early / 5.0-20.0
    myalgia / Early / 0-18.2
    musculoskeletal pain / Early / 0-15.4
    rash (unspecified) / Early / 0-15.0
    alopecia / Delayed / 1.0-13.2
    fatigue / Early / 1.0-11.1
    vomiting / Early / 4.4-6.5
    stool discoloration / Delayed / 4.0-6.0
    dyspepsia / Early / 4.0-6.0
    tenesmus / Delayed / 4.0-6.0
    steatorrhea / Delayed / 4.0-6.0
    pruritus / Rapid / 1.0-4.0
    flushing / Rapid / 1.0-4.0
    arthralgia / Delayed / 1.0-4.0
    increased urinary frequency / Early / 1.0-4.0
    urticaria / Rapid / 0-1.0
    tremor / Early / 0-1.0
    anxiety / Delayed / 0-1.0
    syncope / Early / 0-1.0
    paranoia / Early / 0-1.0
    vertigo / Early / 0-1.0
    weakness / Early / 0-1.0
    epistaxis / Delayed / 0-1.0
    infection / Delayed / 0-1.0
    injection site reaction / Rapid / 10.0
    weight loss / Delayed / Incidence not known
    amenorrhea / Delayed / Incidence not known
    gynecomastia / Delayed / Incidence not known
    oligomenorrhea / Delayed / Incidence not known
    menstrual irregularity / Delayed / Incidence not known
    arthropathy / Delayed / Incidence not known
    drowsiness / Early / Incidence not known
    petechiae / Delayed / Incidence not known
    sinusitis / Delayed / Incidence not known

    DRUG INTERACTIONS

    Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously with other drugs that are associated with QT prolongation, such as octreotide.
    Acebutolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as dihydrocodeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Acetaminophen; Codeine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Acetaminophen; Hydrocodone: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Acetaminophen; Oxycodone: (Major) Octreotide can cause additive constipation with opiate agonists such as oxycodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use. Also, coadministration of octreotide, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Acetaminophen; Propoxyphene: (Moderate) Octreotide can cause additive constipation with opiate agonists such as propoxyphene. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Alfentanil: (Moderate) Octreotide can cause additive constipation with opiate agonists such as alfentanil. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Alfuzosin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), alfuzosin and octreotide should be used together cautiously. Based on electrophysiology studies performed by the manufacturer, alfuzosin may prolong the QT interval in a dose-dependent manner. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Aliskiren; Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Alogliptin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Alogliptin; Metformin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Alogliptin; Pioglitazone: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Alpha-glucosidase Inhibitors: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Amiodarone: (Major) The concomitant use of amiodarone and other drugs known to prolong the QT interval, such as octreotide, should only be done after careful assessment of risks versus benefits, especially when the coadministered agent might decrease the metabolism of amiodarone. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Atorvastatin: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Benazepril: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Olmesartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Telmisartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amlodipine; Valsartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Clarithromycin is associated with an established risk for QT prolongation and TdP. (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Clarithromycin is associated with an established risk for QT prolongation and TdP. (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported with anagrelide. In addition, dose-related increases in mean QTc and heart rate were observed in healthy subjects. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with anagrelide include octreotide.
    Apomorphine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), octreotide and apomorphine should be used together cautiously. Limited data indicate that QT prolongation is possible with apomorphine administration; the change in QTc interval is not significant in most patients receiving dosages within the manufacturer's guidelines. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of octreotide with aprepitant due to substantially increased exposure of aprepitant. If coadministration cannot be avoided, use caution and monitor for an increase in aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Octreotide is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with a moderate CYP3A4 inhibitor, diltiazem, increased the aprepitant AUC 2-fold with a concomitant 1.7-fold increase in the diltiazem AUC; clinically meaningful changes in ECG, heart rate, or blood pressure beyond those induced by diltiazem alone did not occur.
    Aripiprazole: (Moderate) Because both octreotide and aripiprazole are associated with a possible risk for QT prolongation and torsade de pointes (TdP), the combination should be used cautiously and with close monitoring. In addition, because aripiprazole is partially metabolized by CYP3A4, increased aripiprazole blood levels may occur when the drug is coadministered with inhibitors of CYP3A4. Octreotide suppresses growth hormone secretion, which may decrease the metabolic clearance of drugs metabolized by CYP3A4. If these agents are used in combination, the patient should be carefully monitored for aripiprazole-related adverse reactions. In addition, because aripiprazole is also metabolized by CYP2D6, patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. There are no dosing recommendations for Aristada during use of a mild to moderate CYP3A4 inhibitor.
    Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with arsenic trioxide include octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Artemether; Lumefantrine: (Major) Concurrent use of octreotide and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if octreotide must be used with or after artemether; lumefantrine treatment. Administration of artemether; lumefantrine is associated with prolongation of the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Asenapine: (Major) Asenapine has been associated with QT prolongation. According to the manufacturer, asenapine should be avoided in combination with other agents also known to have this effect (e.g., octreotide). Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as dihydrocodeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Aspirin, ASA; Omeprazole: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Aspirin, ASA; Oxycodone: (Major) Octreotide can cause additive constipation with opiate agonists such as oxycodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use. Also, coadministration of octreotide, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Atazanavir: (Moderate) Caution is warranted when atazanavir is administered with octreotide as there is a potential for elevated concentrations of atazanavir. Clinical monitoring for adverse effects is recommended during coadministration. Octreotide inhibits CYP3A4; atazanavir is a CYP3A4 substrate.
    Atazanavir; Cobicistat: (Moderate) Caution is warranted when atazanavir is administered with octreotide as there is a potential for elevated concentrations of atazanavir. Clinical monitoring for adverse effects is recommended during coadministration. Octreotide inhibits CYP3A4; atazanavir is a CYP3A4 substrate. (Moderate) Caution is warranted when cobicistat is administered with octreotide as there is a potential for elevated concentrations of cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Octreotide inhibits CYP3A4; cobicistat is a CYP3A4 substrate.
    Atenolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Atenolol; Chlorthalidone: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Atomoxetine: (Moderate) The concomitant use of atomoxetine and octreotide may lead to additive QT interval prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Atropine; Difenoxin: (Moderate) Diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with octreotide may increase the risk of serious GI related adverse events.
    Atropine; Diphenoxylate: (Moderate) Diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with octreotide may increase the risk of serious GI related adverse events.
    Avanafil: (Major) Avanafil is a substrate of and primarily metabolized by CYP3A4. Studies have shown that drugs that inhibit CYP3A4 can increase avanafil exposure. Patients taking moderate CYP3A4 inhibitors including octreotide, should take avanafil with caution and adhere to a maximum recommended adult avanafil dose of 50 mg/day.
    Axitinib: (Moderate) Use caution if coadministration of axitinib with octreotide is necessary, due to the risk of increased axitinib-related adverse reactions. Axitinib is a CYP3A4 substrate. Somatostatin analogs, such as octreotide, decrease growth hormone secretion which in turn may inhibit CYP3A4. Coadministration with a strong CYP3A4/5 inhibitor, ketoconazole, significantly increased the plasma exposure of axitinib in healthy volunteers. The manufacturer of axitinib recommends a dose reduction in patients receiving strong CYP3A4 inhibitors, but recommendations are not available for moderate or weak CYP3A4 inhibitors.
    Azithromycin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), azithromycin and octreotide should be used together cautiously. There have been case reports of QT prolongation and TdP with the use of azithromycin in postmarketing reports. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval.
    Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as octreotide, for more than 14 days should be avoided unless the benefits justify the risks. When administered together, octreotide may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and potentially more adverse reactions. Furthermore, since both drugs are associated with QT prolongation, coadministration may result in additive prolongation of the QT. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
    Belladonna; Opium: (Moderate) Octreotide can cause additive constipation with opiate agonists. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Bendroflumethiazide; Nadolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Bepridil: (Major) Dose adjustments in drugs such as calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Beta-adrenergic blockers: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Betaxolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include octreotide.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include octreotide.
    Bisoprolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering octreotide with boceprevir due to an increased potential for boceprevir-related adverse events. If octreotide dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of octreotide and boceprevir. Octreotide is an inhibitor of the hepatic isoenzyme CYP3A4; boceprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of boceprevir may be elevated.
    Brexpiprazole: (Moderate) Octreotide suppresses growth hormone secretion, which may cause a decrease in the metabolic clearance of drugs metabolized by CYP3A4 such as brexpiprazole. The potential for an interaction exists when octreotide is coadministered with medications that are metabolized by CYP3A4 and also have a narrow therapeutic index. Decreased metabolism of brexpiprazole may lead to clinically important adverse reactions such as extrapyramidal symptoms.
    Brimonidine; Timolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of octreotide. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; octreotide is a moderate inhibitor of CYP3A4. The concomitant treatment of acromegalic patients with bromocriptine and octreotide increased the bromocriptine AUC by 38%.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Bupivacaine; Lidocaine: (Moderate) Concomitant use of systemic lidocaine and octreotide may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; somatostatin analogs decrease growth hormone secretion, which in turn may inhibit 3A4 enzyme function.
    Buprenorphine: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval, such as octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Buprenorphine; Naloxone: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval, such as octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Cabozantinib: (Moderate) Monitor for an increase in cabozantinib-related adverse events if concomitant use with octreotide is necessary. Cabozantinib is primarily metabolized by CYP3A4; somastatin analogs such as octreotide decrease growth hormone secretion, which in turn may inhibit CYP3A4 enzyme function. Coadministration with a strong CYP3A4 inhibitor, ketoconazole (400 mg daily for 27 days), increased cabozantinib (single dose) exposure by 38%. The manufacturer of cabozantinib recommends a dose reduction when used with strong CYP3A4 inhibitors; however, recommendations are not available for concomitant use with a moderate inhibitor of CYP3A4.
    Canagliflozin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Canagliflozin; Metformin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Carbonic anhydrase inhibitors: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
    Carteolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Carvedilol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and octreotide; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Chloroquine: (Major) Avoid coadministration of chloroquine with octreotide if possible, due to the risk of QT prolongation and torsade de pointes (TdP). Chloroquine administration is associated with an increased risk of QT prolongation and TdP. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Chlorpheniramine; Codeine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as dihydrocodeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as dihydrocodeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Chlorpheniramine; Hydrocodone: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Chlorpromazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), octreotide and chlorpromazine should be used together cautiously. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. In addition, antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as chlorpromazine, may produce additive effects with antidiarrheals if used concomitantly.
    Ciprofloxacin: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering octreotide with ciprofloxacin. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide therapy could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Ciprofloxacin is associated with a possible risk for QT prolongation and TdP.
    Cisapride: (Severe) Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Because of the potential for TdP, use of cisapride with octreotide is contraindicated.
    Citalopram: (Major) Concurrent use of citalopram with octreotide is not recommended due to the potential for QT prolongation and torsade de pointes (TdP). If concurrent therapy is considered essential, ECG monitoring is recommended. Citalopram causes dose-dependent QT interval prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Clarithromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Clarithromycin is associated with an established risk for QT prolongation and TdP.
    Clevidipine: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Clindamycin: (Moderate) Concomitant use of clindamycin and octreotide may decrease clindamycin clearance and increase the risk of adverse reactions. Clindamycin is a CYP3A4 substrate; octreotide is a moderate inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
    Clozapine: (Major) Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause QT prolongation such as octreotide. In addition, antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as clozapine, may produce additive effects with antidiarrheals if used concomitantly. Clozapine is metabolized by CYP1A2, CYP3A4, and CYP2D6. Octreotide suppresses growth hormone secretion, which may decrease the metabolic clearance of drugs metabolized by CYP3A4; therefore, increased concentrations of clozapine may occur during concurrent administration of octreotide.Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with an inhibitor of CYP3A4 should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
    Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with octreotide as there is a potential for elevated concentrations of cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Octreotide inhibits CYP3A4; cobicistat is a CYP3A4 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with octreotide as there is a potential for elevated concentrations of cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Octreotide inhibits CYP3A4; cobicistat is a CYP3A4 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with octreotide as there is a potential for elevated concentrations of cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Octreotide inhibits CYP3A4; cobicistat is a CYP3A4 substrate.
    Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic octreotide therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of octreotide is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of octreotide, resume cobimetinib at the previous dose. Use an alternative to octreotide in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a CYP3A substrate in vitro, and octreotide is a moderate inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
    Codeine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Codeine; Guaifenesin: (Moderate) Octreotide can cause additive constipation with opiate agonists such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Codeine; Phenylephrine; Promethazine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use. (Moderate) Use octreotide cautiously in patients receiving promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Codeine; Promethazine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as codeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use. (Moderate) Use octreotide cautiously in patients receiving promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Conivaptan: (Moderate) Conivaptan is a substrate of CYP3A4. Coadministration of conivaptan with CYP3A4 inhibitors could lead to an increase in conivaptan serum concentrations. According to the manufacturer, coadministration of conivaptan with strong CYP3A4 inhibitors (e.g., ketoconazole) is contraindicated. Until the further data are available, it is prudent to coadminister conivaptan with caution or to avoid coadministering conivaptan with drugs known to be significant inhibitors of CYP3A4 isoenzymes, such as octreotide.
    Crizotinib: (Major) Monitor electrolytes, ECGs for QT prolongation, and for an increase in crizotinib-related adverse reactions if coadministration with octreotide is necessary. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation. Somatostatin analogs, such as octreotide, decrease growth hormone secretion which in turn may inhibit CYP3A4. Additionally, arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Cyanocobalamin, Vitamin B12: (Minor) Depressed levels of cyanocobalamin, vitamin B12, and abnormal Schilling's test have been reported in patients receiving octreotide.
    Cyclobenzaprine: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval such as cyclobenzaprine. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Cyclobenzaprine is associated with a possible risk of QT prolongation and TdP, particularly in the event of acute overdose. Also, antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as cyclobenzaprine, may produce additive effects with antidiarrheals if used concomitantly.
    Cyclophosphamide: (Moderate) Use caution if cyclophosphamide is used concomitantly with octreotide, and monitor for possible changes in the efficacy or toxicity profile of cyclophosphamide. The clinical significance of this interaction is unknown. Cyclophosphamide is a prodrug that is hydroxylated and activated primarily by CYP2B6; the contribution of CYP3A4 to the activation of cyclophosphamide is variable. Additional isoenzymes involved in the activation of cyclophosphamide include CYP2A6, 2C9, 2C18, and 2C19. N-dechloroethylation to therapeutically inactive but neurotoxic metabolites occurs primarily via CYP3A4. The active metabolites, 4-hydroxycyclophosphamide and aldophosphamide, are then inactivated by aldehyde dehydrogenase-mediated oxidation. Octreotide is a moderate CYP3A4 inhibitor; conversion of cyclophosphamide to its active metabolites may be affected. In vitro, coadministration with troleandomycin, a CYP3A4 inhibitor, had little-to-no effect on cyclophosphamide metabolism. However, concurrent use of cyclophosphamide conditioning therapy with itraconazole (a strong CYP3A4 inhibitor) and fluconazole (a moderate CYP3A4 inhibitor) in a randomized trial resulted in increases in serum bilirubin and creatinine, along with increased exposure to toxic cyclophosphamide metabolites (n = 197).
    Cyclosporine: (Major) Octreotide may induce cyclosporine metabolism, thereby increasing the clearance of cyclosprone. In addition, administration of octreotide to patients receiving oral cyclosporine has been shown to decrease the oral bioavailability of cyclosporine. Since oral cyclosporine is administered in an olive oil vehicle, the mechanism of this interaction is thought to be due to the decreased absorption of fat by octreotide. If octreotide is added to an existing cyclosporine regimen, monitor cyclosporine concentrations closely to avoid loss of clinical efficacy until a new steady-state concentration is achieved. Conversely, if octreotide is discontinued, cyclosporine concentrations could increase.
    Daclatasvir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with octreotide, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
    Dapagliflozin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Dapagliflozin; Metformin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Dapagliflozin; Saxagliptin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Darunavir: (Moderate) Caution is warranted when darunavir is administered with octreotide as there is a potential for elevated concentrations of darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Octreotide inhibits CYP3A4; darunavir is a CYP3A4 substrate.
    Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with octreotide as there is a potential for elevated concentrations of cobicistat. Clinical monitoring for adverse effects is recommended during coadministration. Octreotide inhibits CYP3A4; cobicistat is a CYP3A4 substrate. (Moderate) Caution is warranted when darunavir is administered with octreotide as there is a potential for elevated concentrations of darunavir. Clinical monitoring for adverse effects is recommended during coadministration. Octreotide inhibits CYP3A4; darunavir is a CYP3A4 substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) An increased risk of adverse events, including torsade de pointes (TdP), and elevated plasma concentrations of dasabuvir, paritaprevir, and ritonavir may occur if octreotide and dasabuvir; ombitasvir; paritaprevir; ritonavir are used concomitantly. Caution is warranted, along with careful monitoring of patients for adverse events. While dasabuvir; ombitasvir; paritaprevir; ritonavir did not prolong the QTc interval to a clinically relevant extent in healthy subjects, ritonavir has been associated with QT prolongation in other trials. Bradycardia is a risk factor for development of torsade de pointes (TdP), and sinus bradycardia has occurred during octreotide therapy. The potential for bradycardia during octreotide administration theoretically increases the risk of TdP in patients receiving drugs that prolong the QT interval, such as ritonavir. There is also the potential for elevated ritonavir concentrations, further increasing the risk for serious adverse events, as octreotide is expected to inhibit the CYP3A4 metabolism of ritonavir. Paritaprevir and dasabuvir (minor) are also CYP3A4 substrates; elevated concentrations may be seen. (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include octreotide. There is also the potential for elevated ritonavir concentrations, further increasing the risk for serious adverse events, as octreotide is expected to inhibit the CYP3A4 metabolism of ritonavir.
    Dasatinib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), octreotide and dasatinib should be used together cautiously. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Daunorubicin: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy (see Adverse Reactions), warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin or doxorubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with octreotide. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; octreotide suppresses growth hormone secretion, which may decrease the metabolic clearance of drugs metabolized by CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
    Degarelix: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include degarelix.
    Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with octreotide. Halogenated anesthetics can prolong the QT interval. Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Deutetrabenazine: (Moderate) For patients taking a deutetrabenazine dosage more than 24 mg/day with octreotide, assess the QTc interval before and after increasing the dosage of either medication. Clinically relevant QTc prolongation may occur with deutetrabenazine. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval.
    Dexlansoprazole: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Dextromethorphan; Promethazine: (Moderate) Use octreotide cautiously in patients receiving promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Dextromethorphan; Quinidine: (Major) Limited data indicate that somatostatin analogs may inhibit the clearance of drugs metabolized by CYP isoenzymes; this may be due to the suppression of growth hormones. Coadminister octreotide cautiously with drugs that have a narrow therapeutic index and are metabolized by CYP3A4, such as quinidine, as octreotide may inhibit drug metabolism. In addition, until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval, such as quinidine. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as dihydrocodeine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Diltiazem: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Disopyramide: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Disopyramide is a substrate for CYP3A4. Life-threatening interactions have been reported with the coadministration of disopyramide with clarithromycin and erythromycin, both have a possible risk for QT prolongation and TdP and inhibit CYP3A4. The coadministration of disopyramide and CYP3A4 inhibitors may result in a potentially fatal interaction. Drugs with a possible risk for QT prolongation and TdP that are also inhibitors of CYP3A4 that should be used cautiously with disopyramide include octreotide. In addition, octreotide decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as disopyramide, may produce additive effects with antidiarrheals if used concomitantly.
    Dofetilide: (Severe) Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and TdP. Because of the potential for TdP, use of dofetilide with octreotide is contraindicated.
    Dolasetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and octreotide should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval such as dolasetron.
    Donepezil: (Major) Use caution if coadministration of donepezil and octreotide is necessary due to the potential for QT prolongation and torsade de pointes (TdP). Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Donepezil; Memantine: (Major) Use caution if coadministration of donepezil and octreotide is necessary due to the potential for QT prolongation and torsade de pointes (TdP). Case reports indicate that QT prolongation and TdP can occur during donepezil therapy. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Dorzolamide; Timolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Doxorubicin: (Moderate) Octreotide is an inhibitor of CYP3A4 and doxorubicin is a major substrate of CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Additionally, acute cardiotoxicity can occur during the administration of doxorubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported. Octreotide also has a possible risk for QT prolongation and torsades de pointes (TdP). Avoid coadministration of octreotide and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
    Dronabinol, THC: (Major) Use caution if coadministration of dronabinol with octreotide is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; octreotide is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
    Dronedarone: (Severe) Concomitant use of dronedarone and octreotide is contraindicated. Dronedarone is metabolized by CYP3A. Octreotide is an inhibitor CYP3A4. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
    Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include octreotide.
    Efavirenz: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therap. Since bradycardia is a risk factor for development of TdP , the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval, such as efavirenz. In addition, concurrent use may increase the systemic concentration of efavirenz. Efavirenz is a CYP3A4 substrate, while octreotideis a CYP3A4 inhibitor.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therap. Since bradycardia is a risk factor for development of TdP , the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval, such as efavirenz. In addition, concurrent use may increase the systemic concentration of efavirenz. Efavirenz is a CYP3A4 substrate, while octreotideis a CYP3A4 inhibitor.
    Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with octreotide may cause the plasma concentrations of elbasvir and grazoprevir to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Octreotide is a moderate inhibitor of CYP3A; both elbasvir and grazoprevir are metabolized by CYP3A. If these drugs are used together, closely monitor for signs of hepatotoxicity.
    Eliglustat: (Major) Coadminister octreotide and eliglustat with caution. Although there is limited data, it may be prudent to avoid use of these drugs together in intermediate or poor CYP2D6 metabolizers (IMs or PMs). In extensive metabolizers (EMs), dosage reduction of eliglustat to 84 mg PO once daily is recommended. The coadministration of eliglustat with both octreotide and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Both eliglustat and octreotide have the potential to independently prolong the QT interval, and coadministration increases this risk. Eliglustat is a CYP2D6 and CYP3A substrate that is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Limited data suggest octreotide decreases the metabolic clearance of drugs metabolized by CYP3A, most likely due the suppression of growth hormones. In addition, arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, theoretically increasing the risk of torsade de pointes (TdP) in patients receiving drugs that can prolong the QT interval. Coadministration of these agents together may result in additive effects on the QT interval and, potentially, increased plasma concentrations of eliglustat, further increasing the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias). The intensity of this effect depends on CYP2D6 metabolizer status and the pathway of inhibition. For example, in CYP2D6 PMs eliglustat exposure is significantly affected by any degree of CYP3A inhibition because a larger portion of the eliglustat dose is metabolized through this pathway.
    Empagliflozin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Empagliflozin; Linagliptin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents, such as linagliptin, can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Empagliflozin; Metformin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Enalapril; Felodipine: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Enflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with octreotide. Halogenated anesthetics can prolong the QT interval. Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Epirubicin: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering octreotide with epirubicin. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Acute cardiotoxicity can also occur during administration of epirubicin; although, the incidence is rare. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Eplerenone: (Major) Eplerenone is metabolized by the CYP3A4 pathway. Octreotide inhibits the hepatic CYP3A4 isoenzyme and therefore may increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension. If these medications are given concurrently in post-myocardial infarction patients with heart failure, do not exceed an eplerenone dose of 25 mg PO once daily. If these medications are given concurrently, and eplerenone is used for hypertension, initiate eplerenone at 25 mg PO once daily. The dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response.
    Eribulin: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
    Erlotinib: (Moderate) Use caution if coadministration of erlotinib with octreotide is necessary due to the risk of increased erlotinib-related adverse reactions, and avoid coadministration with erlotinib if the patient is additionally taking a CYP1A2 inhibitor. If the patient is taking both octreotide and a CYP1A2 inhibitor and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements; the manufacturer of erlotinib makes the same recommendations for toxicity-related dose reductions in patients taking strong CYP3A4 inhibitors without concomitant CYP1A2 inhibitors. Erlotinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2. Octreotide decreases growth hormone secretion, which in turn may inhibit CYP3A4 enzyme function. Coadministration of erlotinib with ketoconazole, a strong CYP3A4 inhibitor, increased the erlotinib AUC by 67%. Coadministration of erlotinib with ciprofloxacin, a moderate inhibitor of CYP3A4 and CYP1A2, increased the erlotinib AUC by 39% and the Cmax by 17%; coadministration with octreotide may also increase erlotinib exposure.
    Erythromycin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Erythromycin is associated with prolongation of the QT interval and TdP.
    Erythromycin; Sulfisoxazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering erythromycin with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Erythromycin is associated with prolongation of the QT interval and TdP.
    Escitalopram: (Moderate) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as octreotide, should be done with caution and close monitoring.
    Esmolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Esomeprazole: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Esomeprazole; Naproxen: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Ethinyl Estradiol; Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as octreotide may increase the serum concentration of etonogestrel.
    Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as octreotide may increase the serum concentration of etonogestrel.
    Etoposide, VP-16: (Major) Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with octreotide. Octreotide is an inhibitor of CYP3A4 and etoposide, VP-16 is a CYP3A4 substrate. Coadministration may increase etoposide concentrations.
    Everolimus: (Minor) Octreotide is an inhibitor of CYP3A4 and everolimus is a substrate and inhibitor. Concomitant use of depot octreotide with everolimus resulted in a 50% increased octreotide Cmin. The clinical significance of this interaction is not known.
    Ezogabine: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include ezogabine.
    Felodipine: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Fentanyl: (Moderate) Octreotide can cause additive constipation with opiate agonists such as fentanyl. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Fingolimod: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include fingolimod. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia.
    Flecainide: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include flecainide.
    Flibanserin: (Severe) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as octreotide, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
    Fluconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering fluconazole with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Fluconazole has been associated with QT prolongation and rare cases of TdP.
    Fluoxetine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include octreotide.
    Fluoxetine; Olanzapine: (Major) Because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include octreotide. (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering olanzapine with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Fluphenazine: (Minor) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with octreotide include fluphenazine. Also, antidiarrheals decrease GI motility. The concurrent use of phenothiazines with antidiarrheals may produce additive GI effects. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon.
    Fluvoxamine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and octreotide. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval.
    Food: (Moderate) The incidence of marijuana associated adverse effects may change following coadministration with octreotide. Octreotide is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of marijuana's most psychoactive compound, delta-9-tetrahydrocannabinol (Delta-9-THC). When given concurrently with octreotide, the amount of Delta-9-THC converted to the active metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-OH-THC) may be reduced. These changes in Delta-9-THC and 11-OH-THC plasma concentrations may result in an altered marijuana adverse event profile.
    Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as octreotide. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
    Gallium Ga 68 Dotatate: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects. (Moderate) Use caution with the administration of non-radioactive somatostatin analogs, such as octreotide, and gallium Ga 68 dotatate as these may competitively bind to the same somatostatin receptors as gallium Ga 68 dotatate. Image patients with gallium Ga 68 dotatate just prior to dosing with long-acting dosage forms of octreotide. Short-acting dosage forms of octreotide can be used up to 24 hours before imaging with gallium Ga 68 dotatate.
    Gefitinib: (Major) Monitor for an increased incidence of gefitinib-related adverse effects if gefitinib and octreotide are used concomitantly. Gefitinib is metabolized significantly by CYP3A4 and octreotide is a moderate CYP3A4 inhibitor; coadministration may decrease the metabolism of gefitinib and increase gefitinib concentrations. While the manufacturer has provided no guidance regarding the use of gefitinib with mild or moderate CYP3A4 inhibitors, administration of a single 250 mg gefitinib dose with a strong CYP3A4 inhibitor (itraconazole) increased the mean AUC of gefitinib by 80%.
    Gemifloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering octreotide with gemifloxacin. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring in high risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential for octretotide associated bradycardia could theoretically increase the risk of TdP in patients receiving QT prolonging drugs. Gemifloxacin may prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
    Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and octreotide together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Glipizide; Metformin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Glyburide; Metformin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Goserelin: (Moderate) Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with goserelin include octreotide.
    Granisetron: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and octreotide should be used together cautiously. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron with drugs known to prolong the QT interval or are arrhythmogenic, may result in clinical consequences. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Guaifenesin; Hydrocodone: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Halofantrine: (Major) Arrhythmias and conduction disturbances have occurred during octreotide therapy. QT prolongation has also been reported rarely, although no causal relationship has been established. Until further data are available, use octreotide with caution in patients receiving drugs which have potential to prolong the QT interval including halofantrine.
    Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with octreotide. Halogenated anesthetics can prolong the QT interval. Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Haloperidol: (Major) Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Although QT prolongation has been reported rarely with octreotide, no causal relationship has been established relative to the development of torsades de pointes (TdP). Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs which prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs which have been established to have a causal association with QT prolongation and TdP include haloperidol.
    Halothane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with octreotide. Halogenated anesthetics can prolong the QT interval. Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Homatropine; Hydrocodone: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Hydrocodone: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Hydrocodone; Ibuprofen: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Hydrocodone; Phenylephrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Hydrocodone; Pseudoephedrine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydrocodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Hydromorphone: (Moderate) Octreotide can cause additive constipation with opiate agonists such as hydromorphone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and octreotide. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes (TdP) have been reported with the use of hydroxychloroquine. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Hydroxyzine: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include octreotide.
    Ibrutinib: (Major) If coadministered with octreotide, initiate ibrutinib therapy at a reduced dose of 140 mg/day PO for the treatment of B-cell malignancy or 420 mg/day PO for the treatment of chronic graft-versus-host disease; monitor patients more frequently for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). Ibrutinib is a CYP3A4 substrate; octreotide is a moderate CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of another moderate CYP3A4 inhibitor, the Cmax and AUC values of ibrutinib were increased by 3.4-fold and 3-fold, respectively.
    Ibuprofen; Oxycodone: (Major) Octreotide can cause additive constipation with opiate agonists such as oxycodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use. Also, coadministration of octreotide, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Ibutilide: (Major) Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Administer octreotide cautiously in patients receiving ibutilide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Idarubicin: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Acute cardiotoxicity can occur during administration of daunorubicin, doxorubicin, epirubicin, and idarubicin; cumulative, dose-dependent cardiomyopathy may also occur. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported.
    Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease.
    Incretin Mimetics: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with octreotide due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Inotuzumab has been associated with QT interval prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Insulins: (Moderate) Monitor patients receiving octreotide concomitantly with insulin for changes in glycemic control and adjust doses of these medications accordingly. Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations.
    Irinotecan Liposomal: (Moderate) Use caution if irinotecan liposomal is coadministered with octreotide due to increased risk of irinotecan-related toxicity. Octreotide decreases growth hormone secretion, which may inhibit CYP3A4 function. The metabolism of liposomal irinotecan has not been evaluated; however, coadministration of ketoconazole, a strong CYP3A4 and UGT1A1 inhibitor, with non-liposomal irinotecan HCl resulted in increased exposure to both irinotecan and its active metabolite, SN-38.
    Irinotecan: (Moderate) Octreotide is a moderate inhibitor of CYP3A4; irinotecan is a CYP3A4 substrate. Coadministration may result in increased irinotecan exposure. Use caution if concomitant use is necessary and monitor for increased irinotecan side effects, including diarrhea, nausea, vomiting, and myelosuppression.
    Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with octreotide may result in increased serum concentrations of isavuconazonium and an increased risk of adverse effects. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; octreotide is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
    Isoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with octreotide. Halogenated anesthetics can prolong the QT interval. Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Isradipine: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Itraconazole: (Major) Itraconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with itraconazole include octreotide.
    Ivabradine: (Moderate) Use caution during coadministration of ivabradine and octreotide as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; octreotide suppresses growth hormone secretion, which may cause a decrease in the metabolic clearance of drugs metabolized by CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
    Ivacaftor: (Major) Use caution when administering ivacaftor and octreotide concurrently; increased monitoring and/or dose reduction of ivacaftor may be necessary. The manufacturer recommends administering ivacaftor at the usual recommended dose but reducing the frequency to once daily when used concurrently with a moderate CYP3A inhibitor. Ivacaftor is a CYP3A substrate, and octreotide is a CYP3A inhibitor. Coadministration with fluconazole, a moderate CYP3A inhibitor, increased ivacaftor exposure by 3-fold.
    Ketoconazole: (Major) Ketoconazole has been associated with prolongation of the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ketoconazole include octreotide.
    Labetalol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Lansoprazole: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Lansoprazole; Naproxen: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Lapatinib: (Major) Consider ECG and electrolyte monitoring if coadministration of lapatinib and octreotide is necessary. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience. Correct hypokalemia or hypomagnesemia prior to lapatinib administration. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Lenvatinib: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with octreotide include lenvatinib. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    Leuprolide: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include octreotide.
    Leuprolide; Norethindrone: (Moderate) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with leuprolide include octreotide.
    Levobetaxolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Levobunolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Levofloxacin: (Major) Concurrent use of octreotide and levofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Additionally, rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin.
    Levorphanol: (Moderate) Octreotide can cause additive constipation with opiate agonists such as levorphanol. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Lidocaine: (Moderate) Concomitant use of systemic lidocaine and octreotide may increase lidocaine plasma concentrations by decreasing lidocaine clearance and therefore prolonging the elimination half-life. Monitor for lidocaine toxicity if used together. Lidocaine is a CYP3A4 and CYP1A2 substrate; somatostatin analogs decrease growth hormone secretion, which in turn may inhibit 3A4 enzyme function.
    Linagliptin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents, such as linagliptin, can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Linagliptin; Metformin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents, such as linagliptin, can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Lithium: (Moderate) Lithium should be used cautiously with octreotide. Lithium has been associated with QT prolongation. Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval.
    Lomefloxacin: (Moderate) Lomefloxacin has been associated with QT prolongation and infrequent cases of arrhythmia. Other medications which may prolong the QT interval, such as octreotide, should be used cautiously when given concurrently with lomefloxacin.
    Long-acting beta-agonists: (Moderate) Until further data are available, administer octreotide cautiously in patients receiving drugs that prolong the QT interval, such as the beta-agonists. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Loop diuretics: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
    Loperamide: (Moderate) Loperamide should be used cautiously and with close monitoring with octreotide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. In addition, the plasma concentrations of loperamide, a CYP3A4 substrate, may be increased when administered concurrently with octreotide, a CYP3A4 inhibitor. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Loperamide; Simethicone: (Moderate) Loperamide should be used cautiously and with close monitoring with octreotide. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. In addition, the plasma concentrations of loperamide, a CYP3A4 substrate, may be increased when administered concurrently with octreotide, a CYP3A4 inhibitor. If these drugs are used together, monitor for cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, TdP, cardiac arrest) and other loperamide-associated adverse reactions, such as CNS effects.
    Lopinavir; Ritonavir: (Major) QT prolongation in patients taking lopinavir; ritonavir has been reported. Coadministration of lopinavir; ritonavir with other drugs that prolong the QT interval, such as octreotide, may result in additive QT prolongation. Caution is advised during concurrent use. (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include octreotide. There is also the potential for elevated ritonavir concentrations, further increasing the risk for serious adverse events, as octreotide is expected to inhibit the CYP3A4 metabolism of ritonavir.
    Lumacaftor; Ivacaftor: (Major) Use caution when administering ivacaftor and octreotide concurrently; increased monitoring and/or dose reduction of ivacaftor may be necessary. The manufacturer recommends administering ivacaftor at the usual recommended dose but reducing the frequency to once daily when used concurrently with a moderate CYP3A inhibitor. Ivacaftor is a CYP3A substrate, and octreotide is a CYP3A inhibitor. Coadministration with fluconazole, a moderate CYP3A inhibitor, increased ivacaftor exposure by 3-fold.
    Lurasidone: (Major) Octreotide suppresses growth hormone secretion, which may decrease the metabolic clearance of drugs metabolized by CYP3A4 such as lurasidone. Concurrent use of lurasidone and octreotide may lead to an increased risk of lurasidone-related adverse reactions. If a moderate inhibitor of CYP3A4 is being prescribed and lurasidone is added in an adult patient, the recommended starting dose of lurasidone is 20 mg/day and the maximum recommended daily dose of lurasidone is 80 mg/day. If a moderate CYP3A4 inhibitor is added to an existing lurasidone regimen, reduce the lurasidone dose to one-half of the original dose. Patients should be monitored for efficacy and toxicity.
    Mannitol: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
    Maprotiline: (Major) QT prolongation has been reported rarely with the use of octreotide and until further data are available, use octreotide with caution in patients receiving drugs which have potential to prolong the QT interval.
    Maraviroc: (Moderate) Use caution if coadministration of maraviroc with octreotide is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and octreotide is a CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
    Mecasermin rinfabate: (Moderate) Octreotide has been shown to lower endogenous plasma IGF-1 concentrations. Combination therapy may lessen the effectiveness of mecasermin, recombinant, rh-IGF-1 by decreasing the amount of available IGF-1.
    Mecasermin, Recombinant, rh-IGF-1: (Moderate) Octreotide has been shown to lower endogenous plasma IGF-1 concentrations. Combination therapy may lessen the effectiveness of mecasermin, recombinant, rh-IGF-1 by decreasing the amount of available IGF-1.
    Mefloquine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), octreotide and mefloquine should be used together cautiously. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
    Meperidine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as meperidine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Meperidine; Promethazine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as meperidine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use. (Moderate) Use octreotide cautiously in patients receiving promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Mesoridazine: (Major) Mesoridazine is associated with a well-established risk of QT prolongation and torsades de pointes and is generally considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval, cause orthostatic hypotension and/or torsade de pointes including octreotide. In addition, drugs that also decrease GI motility, such as mesoridazine, may produce additive effects with antidiarrheals if used concomitantly.
    Metformin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Metformin; Pioglitazone: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Metformin; Repaglinide: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Metformin; Rosiglitazone: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Metformin; Saxagliptin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Metformin; Sitagliptin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added. (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Methadone: (Major) Both octreotide and methadone may cause QT prolongation, although the relationship of QT prolongation to octreotide is not established as many of these patients had underlying cardiac disease. Also, octreotide may decrease the analgesic effect of methadone or morphine. If a loss or decrease in pain control occurs with concomitant therapy, consider discontinuing the octreotide. In a case report, a patient with chondrosarcoma who was receiving chronic methadone experienced a loss of pain control after starting somatostatin as part of a chemotherapy regimen. The patient required increased doses of methadone and was subsequently switched to morphine, intravenous then spinal administration, with no pain relief. After discontinuing the somatostatin, the patient's pain decreased and myosis and sedation occurred for the first time.
    Metoprolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Metronidazole: (Moderate) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with metronidazole include octreotide.
    Midostaurin: (Major) The concomitant use of midostaurin and octreotide may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy.
    Mifepristone, RU-486: (Moderate) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and octreotide should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include octreotide.
    Mirtazapine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of mirtazapine and octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during postmarketing use of mirtazapine, primarily following overdose or in patients with other risk factors for QT prolongation, including concomitant use of other medications associated with QT prolongation.
    Morphine: (Moderate) Octreotide can cause additive constipation with opiate agonists such as morphine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Octreotide may also decrease the analgesic effect of morphine. If a loss or decrease in pain control occurs with concomitant therapy, consider discontinuing the octreotide.
    Morphine; Naltrexone: (Moderate) Octreotide can cause additive constipation with opiate agonists such as morphine. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Octreotide may also decrease the analgesic effect of morphine. If a loss or decrease in pain control occurs with concomitant therapy, consider discontinuing the octreotide.
    Moxifloxacin: (Major) Concurrent use of octreotide and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Moxifloxacin has been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded. Arrhythmias, sinus bradycardia, and conduction disturbances have also occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Nadolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Nateglinide: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. In addition, octreotide may attenuate the hypoglycemic actions of nateglinide. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Nebivolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Nebivolol; Valsartan: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Neratinib: (Major) Avoid concomitant use of octreotide with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate. Somatostatin analogs, such as octreotide, decrease growth hormone secretion which in turn may inhibit CYP3A4. The effect of moderate CYP3A4 inhibition on neratinib concentrations has not been studied; however, coadministration with a strong CYP3A4 inhibitor increased neratinib exposure by 481%. Because of the significant impact on neratinib exposure from strong CYP3A4 inhibition, the potential impact on neratinib safety from concomitant use with moderate CYP3A4 inhibitors should be considered as they may also significantly increase neratinib exposure.
    Nicardipine: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Nifedipine: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Nilotinib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), octreotide and nilotinib should be used together cautiously. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Nilotinib prolongs the QT interval. If concurrent administration is unavoidable, the manufacturer of nilotinib recommends interruption of nilotinib treatment. If nilotinib must be continued, closely monitor the patient for QT interval prolongation.
    Nimodipine: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Nintedanib: (Moderate) Octreotide is a moderate inhibitor of CYP3A4 and nintedanib is a minor CYP3A4 substrate. Coadministration may increase the concentration and clinical effect of nintedanib. If concomitant use of octreotide and nintedanib is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of therapy may be necessary.
    Nisoldipine: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Norfloxacin: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering octreotide with norfloxacin. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Quinolones have been associated with QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Ofloxacin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering octreotide with ofloxacin. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Some quinolones, including ofloxacin, have been associated with QT prolongation. Additionally, post-marketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Moderate) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering olanzapine with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
    Olaparib: (Major) Avoid coadministration of olaparib with octreotide and consider alternative agents with less CYP3A4 inhibition due to increased olaparib exposure. If concomitant use is unavoidable, reduce the dose of olaparib tablets to 150 mg twice daily; reduce the dose of olaparib capsules to 200 mg twice daily. Olaparib is a CYP3A4/5 substrate. Somatostatin analogs, such as octreotide, decrease growth hormone secretion which in turn may inhibit CYP3A4.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) An increased risk of adverse events, including torsade de pointes (TdP), and elevated plasma concentrations of dasabuvir, paritaprevir, and ritonavir may occur if octreotide and dasabuvir; ombitasvir; paritaprevir; ritonavir are used concomitantly. Caution is warranted, along with careful monitoring of patients for adverse events. While dasabuvir; ombitasvir; paritaprevir; ritonavir did not prolong the QTc interval to a clinically relevant extent in healthy subjects, ritonavir has been associated with QT prolongation in other trials. Bradycardia is a risk factor for development of torsade de pointes (TdP), and sinus bradycardia has occurred during octreotide therapy. The potential for bradycardia during octreotide administration theoretically increases the risk of TdP in patients receiving drugs that prolong the QT interval, such as ritonavir. There is also the potential for elevated ritonavir concentrations, further increasing the risk for serious adverse events, as octreotide is expected to inhibit the CYP3A4 metabolism of ritonavir. Paritaprevir and dasabuvir (minor) are also CYP3A4 substrates; elevated concentrations may be seen. (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include octreotide. There is also the potential for elevated ritonavir concentrations, further increasing the risk for serious adverse events, as octreotide is expected to inhibit the CYP3A4 metabolism of ritonavir.
    Omeprazole: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Omeprazole; Sodium Bicarbonate: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Ondansetron: (Major) ECG monitoring is recommended if ondansetron and octreotide must be coadministered. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP). Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Osimertinib: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of octreotide with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of octreotide with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes (TdP) have been reported with oxaliplatin use in postmarketing experience. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Oxycodone: (Major) Octreotide can cause additive constipation with opiate agonists such as oxycodone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use. Also, coadministration of octreotide, a CYP3A4 inhibitor, and oxycodone, a CYP3A4 substrate, may increase oxycodone plasma concentrations and increase or prolong related toxicities including potentially fatal respiratory depression. If therapy with both agents is necessary, monitor patient for an extended period of time and adjust dosage as necessary; oxycodone dosage adjustments may be needed if the CYP3A4 inhibitor is discontinued. Concurrent administration of oxycodone and voriconazole, another CYP3A4 inhibitor, increased oxycodone AUC by 3.6-fold and the Cmax by 1.7-fold.
    Oxymorphone: (Moderate) Octreotide can cause additive constipation with opiate agonists such as oxymorphone. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as octreotide. However, if coadministration is considered necessary by the practitioner, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential.
    Panobinostat: (Major) The co-administration of panobinostat with octreotide is not recommended; QT prolongation has been reported with both agents. Octreotide is a CYP3A4 inhibitor and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking 14 days of a strong CYP3A4 inhibitor. Although an initial panobinostat dose reduction is recommended in patients taking concomitant strong CYP3A4 inhibitors, no dose recommendations with mild or moderate CYP3A4 inhibitors are provided by the manufacturer. If concomitant use of octreotide and panobinostat cannot be avoided, closely monitor electrocardiograms and for signs and symptoms of panobinostat toxicity such as cardiac arrhythmias, diarrhea, bleeding, infection, and hepatotoxicity. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve.
    Pantoprazole: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Pasireotide: (Major) Cautious use of pasireotide and octreotide is needed, as coadministration may have additive effects on the prolongation of the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Pazopanib: (Major) Concurrent use of pazopanib and octreotide is not advised. Closely monitor the patient for QT interval prolongation if coadministration of pazopanib and octreotide cannot be avoided. Pazopanib has been reported to prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Penbutolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Pentamidine: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include pentamidine. Intravenous pentamidine is associated with a risk of QT prolongation.
    Perindopril; Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as octreotide, are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
    Perphenazine: (Minor) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with octreotide include perphenazine. Additive drowsiness or other additive CNS effects may also occur. Antidiarrheals decrease GI motility. The concurrent use of phenothiazines with antidiarrheals may produce additive GI effects. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon.
    Perphenazine; Amitriptyline: (Minor) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with octreotide include perphenazine. Additive drowsiness or other additive CNS effects may also occur. Antidiarrheals decrease GI motility. The concurrent use of phenothiazines with antidiarrheals may produce additive GI effects. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon.
    Phenylephrine; Promethazine: (Moderate) Use octreotide cautiously in patients receiving promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Pimozide: (Severe) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of octreotide with pimozide is contraindicated.
    Pindolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Posaconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering posaconazole with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Posaconazole has been associated with QT prolongation and in rare cases, TdP.
    Potassium-sparing diuretics: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
    Pramlintide: (Major) Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. Medications with the potential to slow GI motility such as octreotide, should be used with caution, if at all, with pramlintide until more data are available from the manufacturer. Monitor blood glucose.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include octreotide.
    Procainamide: (Major) Administer octreotide cautiously in patients receiving procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Prochlorperazine: (Minor) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with octreotide include prochlorperazine. Additive drowsiness or other additive CNS effects may also occur. Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as prochlorperazine, may produce additive effects with antidiarrheals if used concomitantly.
    Promethazine: (Moderate) Use octreotide cautiously in patients receiving promethazine. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Propafenone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering propafenone with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Propafenone, a Class IC antiarrhythmic, increases the QT interval largely due to prolongation of the QRS interval.
    Propoxyphene: (Moderate) Octreotide can cause additive constipation with opiate agonists such as propoxyphene. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Propranolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Proton pump inhibitors: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Quetiapine: (Major) Avoid coadministration of quetiapine and octreotide due to the potential for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Quinidine: (Major) Limited data indicate that somatostatin analogs may inhibit the clearance of drugs metabolized by CYP isoenzymes; this may be due to the suppression of growth hormones. Coadminister octreotide cautiously with drugs that have a narrow therapeutic index and are metabolized by CYP3A4, such as quinidine, as octreotide may inhibit drug metabolism. In addition, until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval, such as quinidine. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Quinine: (Major) Concurrent use of quinine and octreotide should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Arrhythmias, sinus bradycardia, and conduction disturbances have also occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Rabeprazole: (Minor) The effectiveness of proton pump inhibitors may be decreased if given with other antisecretory agents, such as octreotide. Proton pump inhibitors inhibit only actively secreting H+-pumps. Antacids may be used while taking esomeprazole.
    Ranolazine: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with ranolazine include octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease.
    Regadenoson: (Moderate) Regadenoson has been associated with QT prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with regadenoson include octreotide.
    Remifentanil: (Moderate) Octreotide can cause additive constipation with opiate agonists such as remifentanil. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Repaglinide: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Ribociclib: (Major) Avoid coadministration of ribociclib with octreotide due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of ribociclib may be increased resulting in an increase in treatment-related adverse reactions (e.g., neutropenia, QT prolongation). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Concomitant use may increase the risk for QT prolongation. Ribociclib is also extensively metabolized by CYP3A4 and octreotide is a moderate CYP3A4 inhibitor.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with octreotide due to an increased risk for QT prolongation and torsade de pointes (TdP). Additionally, the systemic exposure of ribociclib may be increased resulting in an increase in treatment-related adverse reactions (e.g., neutropenia, QT prolongation). Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Concomitant use may increase the risk for QT prolongation. Ribociclib is also extensively metabolized by CYP3A4 and octreotide is a moderate CYP3A4 inhibitor.
    Rilpivirine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering rilpivirine with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include octreotide. There is also the potential for elevated ritonavir concentrations, further increasing the risk for serious adverse events, as octreotide is expected to inhibit the CYP3A4 metabolism of ritonavir.
    Rivaroxaban: (Minor) Coadministration of rivaroxaban and octreotide may result in increases in rivaroxaban exposure and may increase bleeding risk. Octreotide is an inhibitor of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
    Romidepsin: (Major) Romidepsin is a substrate for CYP3A4. Octreotide is an inhibitor of CYP3A4. Concurrent administration of romidepsin with an inhibitor of CYP3A4 may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary. In addition, romidepsin has been reported to prolong the QT interval. Octreotide may also prolong the QT interval. If romidepsin and octreotide must be continued, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
    Ruxolitinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as octreotide, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure.
    Saquinavir: (Severe) Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval, such as octreotide. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
    Saxagliptin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Sertraline: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval, such as sertraline. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. There have been post-marketing reports of QT prolongation and TdP during treatment with sertraline.
    Sevoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with octreotide. Halogenated anesthetics can prolong the QT interval. Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Short-acting beta-agonists: (Minor) Until further data are available, administer octreotide cautiously in patients receiving drugs that prolong the QT interval, such as the beta-agonists. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Simeprevir: (Major) Avoid concurrent use of simeprevir and octreotide. Octreotide suppresses growth hormone secretion, which may cause a decrease in the metabolic clearance of drugs metabolized by CYP3A4 which may increase the plasma concentrations of simeprevir, resulting in adverse effects.
    Simvastatin; Sitagliptin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Sincalide: (Moderate) Sincalide-induced gallbladder ejection fraction may be affected by concurrent octreotide. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
    Sitagliptin: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents can produce hypoglycemia. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with octreotide. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a substrate of CYP3A4. Octreotide, a somastatin analog, decreases growth hormone secretion which in turn may inhibit CYP3A4 enzyme function.
    Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with octreotide. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Velpatasvir is a substrate of CYP3A4. Octreotide, a somastatin analog, decreases growth hormone secretion which in turn may inhibit CYP3A4 enzyme function.
    Solifenacin: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include solifenacin . Also, antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as solfenacin, may produce additive effects with antidiarrheals if used concomitantly.
    Sorafenib: (Major) ECG monitoring is recommended if coadministration of sorafenib and octreotide is necessary; closely monitor the patient for QT interval prolongation. Sorafenib has been associated with QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Sotalol: (Major) Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Octreotide should be used cautiously with sotalol. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Sparfloxacin: (Major) Sparfloxacin is associated with an established risk for QT prolongation and torsades de pointes and is contraindicated in patients receiving other drugs that can cause QT prolongation including octreotide.
    Sufentanil: (Moderate) Octreotide can cause additive constipation with opiate agonists such as sufentanil. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Monitor patients during concomitant use.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with sulfamethoxazole; trimethoprim include octreotide.
    Sulfonylureas: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Sunitinib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), octreotide and sunitinib should be used together cautiously. Sunitinib can prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Tacrolimus: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), octreotide and tacrolimus should be used together cautiously; tacrolimus exposure may also increase. Monitor tacrolimus whole blood trough concentrations and reduce the tacrolimus dose if necessary. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic index and has been associated with QT prolongation. Somatostatin analogs like octreotide decrease growth hormone secretion which in turn may inhibit 3A4 enzyme function. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Tamoxifen: (Major) Avoid coadministration of tamoxifen with octreotide due to the potential for decreased tamoxifen efficacy and/or increased tamoxifen toxicity; additive QT prolongation may also occur. If coadministration is necessary, monitor for altered tamoxifen efficacy, increased tamoxifen-related adverse effects, and evidence of QT prolongation. Octreotide may reduce the conversion of tamoxifen to other potent active metabolites via inhibition of CYP3A4. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP; the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering octreotide with telaprevir due to an increased potential for telaprevir-related adverse events. If octreotide dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathways of octreotide and telaprevir. Octreotide is an inhibitor of the hepatic isoenzyme CYP3A4; telaprevir is metabolized by this isoenzyme. When used in combination, the plasma concentrations of telaprevir may be elevated.
    Telavancin: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telavancin with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval, such as telavancin.
    Telithromycin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), octreotide and telithromycin should be used together cautiously. Telithromycin is associated with QT prolongation and torsades de pointes (TdP). Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Telotristat Ethyl: (Moderate) Administer short-acting octreotide at least 30 minutes after the administration of telotristat ethyl if concomitant use is necessary. Telotristat ethyl is indicated for use in combination with somatostatin analogs, including octreotide, and patients in clinical trials received rescue treatment with short-acting octreotide and antidiarrheal medications (i.e., loperamide). However, systemic exposures of telotristat ethyl and its active metabolite were significantly decreased by short-acting octreotide in a pharmacokinetic study. When a single telotristat ethyl 500-mg PO dose (twice the recommended dose) was administered with a short-acting octreotide 200-mcg subcutaneous dose, the mean telotristat ethyl Cmax decreased by 86% and the mean telotristat ethyl AUC(0-last) decreased by 81% in healthy volunteers. Additionally, the mean Cmax and AUC(0-last) values for the active metabolite, telotristat, were decreased by 79%, and 68%, respectively.
    Temsirolimus: (Moderate) Use caution if coadministration of temsirolimus with octreotide is necessary, and monitor for an increase in temsirolimus-related adverse reactions. Temsirolimus is a CYP3A4 substrate. Somatostatin analogs, such as octreotide, decrease growth hormone secretion which in turn may inhibit CYP3A4. Coadministration may increase plasma concentrations of temsirolimus (and active metabolite, sirolimus). The manufacturer of temsirolimus recommends a dose reduction if coadministered with a strong CYP3A4 inhibitor, but recommendations are not available for concomitant use of moderate or weak inhibitors. Coadministration of temsirolimus with ketoconazole, a strong CYP3A4 inhibitor, had no significant effect on the AUC or Cmax of temsirolimus, but increased the sirolimus AUC and Cmax by 3.1-fold and 2.2-fold, respectively.
    Terbinafine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering octreotide. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; octreotide is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
    Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc including octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Thiazide diuretics: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
    Thiazolidinediones: (Moderate) Administration of octreotide to patients receiving oral antidiabetic agents or insulin can produce hypoglycemia due to slowing of gut motility which leads to decreased postprandial glucose concentrations. Patients should be monitored closely and doses of these medications adjusted accordingly if octreotide is added.
    Thioridazine: (Severe) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Because of the potential for TdP, use of octreotide with thioridazine is contraindicated. In addition, antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as thioridazine, may produce additive effects with antidiarrheals if used concomitantly.
    Timolol: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Tolterodine: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include tolterodine. Also, antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as tolterodine, may produce additive effects with antidiarrheals if used concomitantly.
    Tolvaptan: (Major) Tolvaptan is metabolized by CYP3A4. Octreotide is a moderate inhibitor of CYP3A4. Coadministration may cause a marked increased in tolvaptan concentrations and should be avoided. In addition, patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide.
    Toremifene: (Major) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner.
    Trabectedin: (Moderate) Use caution if coadministration of trabectedin and octreotide is necessary, due to the risk of increased trabectedin exposure. Trabectedin is a CYP3A substrate; octreotide suppresses growth hormone secretion, which may cause a decrease in the metabolic clearance of drugs metabolized by CYP3A4. Coadministration with ketoconazole (200 mg twice daily for 7.5 days), a strong CYP3A inhibitor, increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% and the Cmax by 22% compared to a single dose of trabectedin (1.3 mg/m2) given alone. The manufacturer of trabectedin recommends avoidance of strong CYP3A inhibitors within 1 day before and 1 week after trabectedin administration; there are no recommendations for concomitant use of moderate or weak CYP3A inhibitors.
    Trandolapril; Verapamil: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Trazodone: (Major) Avoid coadministration of octreotide and trazodone. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
    Tricyclic antidepressants: (Moderate) Coadministration of octreotide with tricyclic antidepressants may increase the risk of QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Also, antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as tricyclic antidepressants, may produce additive effects with antidiarrheals if used concomitantly. Additive CNS effects may also occur.
    Trifluoperazine: (Minor) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs with a possible risk for QT prolongation that should be used cautiously with octreotide include trifluoperazine. Also, antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Other drugs that also decrease GI motility, such as trifluoperazine , may produce additive effects with antidiarrheals if used concomitantly. Additive drowsiness or other additive CNS effects may also occur.
    Triptorelin: (Moderate) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with triptorelin include octreotide.
    Ulipristal: (Minor) Ulipristal is a substrate of CYP3A4 and octreotide is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
    Urea: (Moderate) Patients receiving diuretics or other agents to control fluid and electrolyte balance may require dosage adjustments while receiving octreotide due to additive effects.
    Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose.
    Vardenafil: (Major) Therapeutic (10 mg) and supratherapeutic (80 mg) doses of vardenafil produces an increase in QTc interval (e.g., 4 to 6 msec calculated by individual QT correction). When vardenafil (10 mg) was given with gatifloxacin (400 mg), an additive effect on the QT interval was observed. The effect of vardenafil on the QT interval should be considered when prescribing the drug. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with vardenafil include octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Vemurafenib: (Major) ECG monitoring is recommended if vemurafenib and octreotide must be coadministered; closely monitor the patient for QT interval prolongation. Vemurafenib has been associated with QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of torsade de pointes (TdP), the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Venlafaxine: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with octreotide include venlafaxine.
    Verapamil: (Moderate) Dose adjustments in drugs such as beta-blockers and calcium-channel blockers which cause bradycardia and/or affect cardiac conduction may be necessary during octreotide therapy due to additive effects.
    Vincristine Liposomal: (Major) Octreotide inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vincristine: (Major) Octreotide inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
    Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and octreotide. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 substrate, is coadministered with octreotide, a CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
    Voriconazole: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering voriconazole with octreotide. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Voriconazole has been associated with prolongation of the QT interval and rare cases of arrhythmias, including TdP.
    Vorinostat: (Moderate) Administer octreotide cautiously in patients receiving drugs that prolong the QT interval. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy, warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP, the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval. Until further data are available, it is suggested to use octreotide cautiously in patients receiving drugs which prolong the QT interval. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with octreotide.
    Ziprasidone: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including octreotide.
    Zolpidem: (Moderate) It is advisable to closely monitor zolpidem tolerability and safety during concurrent use of octreotide, a moderate CYP3A4 inhibitor, since CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism. There is evidence of an increase in pharmacodynamics effects and systemic exposure of zolpidem during co-administration with some potent inhibitors of CYP3A4, such as azole antifungals.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no adequate and well-controlled studies of octreotide use during human pregnancy. It is known to cross the human placenta and has been measured in the newborn. Available human pregnancy data are limited. Most women who have taken octreotide during pregnancy have taken it during the first trimester; doses ranged from 200 to 300 mcg/day subcutaneously (injection solution) or 20 to 30 mg/month IM (long-acting depot suspension formulation). In those women who continued it throughout pregnancy and had a known outcome, congenital abnormalities were not reported. The few cases describing octreotide use during some portion of pregnancy resulted in normal outcomes to the fetus. Reproduction studies have been performed in rats and rabbits at doses up to 16-times the highest recommended human dose and have revealed no evidence of harm to the fetus due to octreotide. The drug should only be used during pregnancy if clearly needed.

    Use octreotide with caution in women who are breast-feeding, particularly if the infant is under 2 months of age, due to the minimal data available. It is not known if octreotide is excreted in breast milk. Because the drug is poorly absorbed following oral administration, the risk to the nursing infant appears to be minimal. Documentation of octreotide use during breast-feeding is lacking; however, there is a published report of a woman receiving octreotide for acromegaly who breast-fed for 4 months with no adverse effects or problems with feeding in the infant.

    MECHANISM OF ACTION

    Mechanism of Action: The pharmacologic effects of octreotide are similar to those of somatostatin, a hypothalamic peptide. Although the exact mechanism of action is not known, octreotide is believed to act at somatostatin receptors. Octreotide inhibits the secretion of both pituitary and gastrointestinal hormones including serotonin, gastrin, vasoactive intestinal peptide (VIP), insulin, glucagon, secretin, motilin, pancreatic polypeptide, growth hormone, and thyrotropin. Due to the number of hormones affected by octreotide, the actions of octreotide are diverse. Inhibiting the secretion of serotonin and other gastroentero-pancreatic peptides results in increased intestinal absorption of water and electrolytes, decreased pancreatic and gastric acid secretions, and increased intestinal transit time. In contrast, cisapride, a serotonin receptor agonist, stimulates peristalsis. Thus, with regard to serotonin, octreotide and cisapride exert opposite actions in the GI tract.Octreotide can inhibit the secretion of hormones involved in vasodilation. This property makes octreotide useful in treating variceal bleeding and orthostatic hypotension. Octreotide increases splanchnic arteriolar resistance and decreases gastrointestinal blood flow, hepatic-vein wedge pressure, hepatic blood flow, portal vein pressure, and intravariceal pressure. Decreased blood flow to the portal vein reduces portal venous pressure in patients with cirrhosis or portal hypertension. A majority of patients with portal hypertension have a reduction in variceal bleeding when given octreotide. In patients with orthostatic or postprandial hypotension due to autonomic neuropathy, it is believed that their condition occurs as a result of inadequate sympathetic reflexes in conjunction with splanchnic vasodilation and VIP secretion. Administration of octreotide results in increases in both semirecumbent and standing blood pressures. Octreotide's effects were seen in patients with progressive autonomic failure, multiple-organ-system atrophy, and diabetic autonomic neuropathy but not in patients with sympathotonic orthostatic hypotension. Because octreotide affects many GI hormones, octreotide is useful in controlling many types of secretory diarrhea including patients with VIPomas and AIDS-associated diarrhea. In patients with VIPomas, octreotide reduces serum levels of VIP. As a result, stool volume decreases and hypokalemia and achlorhydria improve. Tachyphylaxis to octreotide, however, has been observed in treating this condition. In patients with AIDS, diarrhea is caused by an infectious agent such as Cryptosporidium or is secondary to HIV infection. Human immunodeficiency virus contains an amino acid sequence similar to VIP which is believed to cause manifestations similar to VIP. Because of its inhibitory effects on VIP, octreotide is effective in patients with diarrhea due to HIV. In patients with carcinoid syndrome, octreotide's ability to inhibit serotonin secretion results in decreased flushing, diarrhea, and wheezing, as well as reduced urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA), the primary metabolite of serotonin. Improvements in the musculoskeletal symptoms of carcinoid have been reported with octreotide. In combination with other therapies, octreotide has also been effective in improving symptoms and decreasing tumor size in patients with metastatic carcinoid tumors.Studies supporting the role of octreotide in the treatment of other gastroenteropancreatic tumors (i.e., gastrinomas, glucagonomas, insulinomas) are limited. In the treatment of gastrinomas (e.g., Zollinger-Ellison syndrome), octreotide may be more costly and no more effective than conventional therapies (H2-antagonists and omeprazole), however, benefit may be derived from combination therapy because octreotide inhibits gastrin release whereas H2-antagonists and omeprazole cause significant increases in gastrin serum concentrations. Octreotide may provide benefits in patients with unresectable insulinomas by decreasing insulin secretion and improving hypoglycemia in patients unresponsive to other therapies. In the treatment of the very rare glucagonomas, octreotide has only demonstrated improvement in the dermatosis (necrolytic migratory dermatitis) associated with this condition and has minimal effects on serum glucagon levels.Octreotide also inhibits the secretion of some anterior pituitary hormones. Octreotide has been studied in the treatment of acromegaly and thyrotropinomas. Octreotide's effects in treating acromegaly results from its inhibition of growth hormone (GH). In acromegalic patients, octreotide reduces serum levels of GH resulting in a decrease in associated symptoms such as headache, hyperhidrosis, arthralgia, and finger circumference. In the treatment of thyrotropinomas, Chanson et al reported that thyroid-stimulating hormone (TSH) levels were decreased in the majority of patients treated with octreotide. Because these tumors are rare, data on the use of octreotide in this condition are limited to case reports. Further investigation is needed to determine octreotide's role as an alternative for patients with thyrotropinomas that are refractory to surgery and radiation.

    PHARMACOKINETICS

    Octreotide acetate is administered parenterally; the immediate-release formulation should be given intravenously or subcutaneously, while the depot formulation should only be given intramuscularly. Approximately 65% of a dose is bound to lipoprotein and albumin in a concentration-dependent manner. The volume of distribution is estimated to be 13.6 L in adult patients. Octreotide undergoes extensive hepatic metabolism. Total body clearance ranges from 7—10 L/hour in adult patients. The apparent elimination half-life of immediate-release octreotide injection is 1.7—1.9 hours, which is significantly greater than somatostatin's half-life of 1—3 minutes. Approximately 32% of a dose is excreted in the urine as unchanged drug.
     
    Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
    Octreotide suppresses growth hormone secretion, which may decrease the metabolic clearance of drugs metabolized by CYP3A4. Potential for drug-drug interactions exists when coadministered with medications that have a narrow therapeutic index and are metabolized by CYP3A4.

    Intravenous Route

    Intravenous and subcutaneous octreotide are bioequivalent; peak concentrations and AUC are dose-proportional.

    Intramuscular Route

    After intramuscular (IM) administration of the long-acting depot formulation, octreotide is slowly released as the glucose star polymer (D,L-lactic and glycolic acids copolymer) biodegrades in the muscle, primarily through hydrolysis. Once octreotide is released from the polymer, it has the same pharmacokinetic and mechanistic characteristics as the immediate-release dosage form. The relative bioavailability of the depot injection as compared to the immediate release injection given subcutaneously is 60—63%. After a single IM injection in healthy adult patients, peak serum concentrations reach a transient initial peak of 0.03 ng/ml/mg within 1 hour. Subsequently, concentrations decline over 3—5 days (nadir < 0.01 ng/ml/mg) before increasing and reaching a plateau 2—3 weeks after injection. Plateau concentrations are maintained for 2—3 weeks, with dose-proportional peak concentrations of 0.07 ng/ml/mg. Octreotide concentrations start to decrease slowly 6 weeks after the IM injection. By week 12—13, serum concentrations are < 0.01 ng/ml/mg. After multiple injections of the depot formulation given every 4 weeks, steady state serum concentrations are reached after the third dose. After administration of octreotide depot injection 20 mg and 30 mg every 4 weeks in adult patients, respective steady-state concentrations are 1.6 ng/ml and 2.6 ng/ml at peak and 1.2 ng/ml and 2.1 ng/ml at trough. The depot formulation has smaller peak-to-trough concentration variations than the 3 times daily subcutaneous injections (44—68% vs 163—209%, respectively).

    Subcutaneous Route

    Octreotide is absorbed rapidly and completely after subcutaneous (SC) injection. Distribution of octreotide from plasma occurs rapidly, with an apparent distribution half-life of 12 minutes. In adult patients, peak concentrations of 5.2 ng/ml occur within 25 minutes after a 100 mcg dose. The effects of SC octreotide are variable but can last for up to 12 hours, depending on the indication for use.