LANREOTIDE ACETATE (Generic for SOMATULINE DEPOT)

Lanreotide is an analog of the naturally occurring hormone somatostatin. Lanreotide is used to normalize growth hormone (GH) and insulin growth factor-1 (IGF-1) concentrations in patients with acromegaly who either have had an inadequate response to surgery or radiotherapy or are not candidates for such modes of treatment. Clinical studies of lanreotide for acromegaly demonstrate that, after approximately 1 year of treatment, 51% to 86% of patients experience decreases of GH concentrations to within normal limits and 38% to 41% experience normalization of both GH and IGF-1 concentrations. Similar to octreotide, lanreotide is also used to minimize the symptoms associated with carcinoid neuroendocrine tumors (NET) including diarrhea, abdominal pain, and flushing. Data indicate that lanreotide exhibits antiproliferative effects on these NET tumors. Lanreotide is also used to treat the symptoms of hyperthyroidism in patients with TSH-secreting pituitary tumors.

General Administration Information
For storage information, see specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration, whenever solution and container permit.
Subcutaneous Administration
-Lanreotide depot injection is administered via deep subcutaneous (SC) injection only.
Preparation:
-30 minutes prior to injection, remove the sealed syringe pouch from the refrigerator and allow it to come to room temperature. Keep pouch sealed until just before injection.
-The content of the prefilled syringe should have a viscous, gel-like appearance and may also contain micro bubbles that can clear up during injection. This is normal and does not interfere with the quality of the product.
-Product left in its sealed pouch may be returned to the refrigerator for continued storage and later use if kept at room temperature (less than 104 degrees F or 40 degrees C) for up to 72 hours.

Administration:
-Inject and administer medication slowly over 20 seconds via deep subcutaneous injection into the superior external quadrant (outer area) of the buttock.

-Alternate injection sites between the right and left sides of the buttocks with each injection.

The most commonly reported adverse reactions during clinical trials of lanreotide in patients with acromegaly were gastrointestinal in nature and were mild to moderate in severity. Diarrhea was reported in 26% to 65% of these patients and appears to be dose-related; abdominal pain (9% to 20%) and flatulence (less than or equal to 14%) also appeared to be dose related. Loose stools occurred in 6% to 9% of lanreotide-treated acromegaly patients. It should be noted that when used for the symptomatic relief of neuroendocrine carcinoid tumors, diarrhea typically improves with lanreotide administration. Other gastrointestinal-related adverse reactions reported include nausea (9% to 11%), vomiting (5% to 7%), constipation (5% to 8%), and weight loss (8% to 11%). In patients treated with lanreotide for gastroenteropancreatic neuroendocrine tumor (GEP-NET), abdominal pain occurred in 34% of patients (grade 3 or 4, 6%) and vomiting in 19% (grade 3 or 4, 2%); adverse reactions in patients with carcinoid syndrome were similar to those in the GEP-NET population. Steatorrhea has been reported with lanreotide use in postmarketing experience.

There have been postmarketing reports of cholelithiasis (gallstones) resulting in complications, including cholecystitis, cholangitis, and pancreatitis, and requiring cholecystectomy in patients taking lanreotide depot. Patients may need to be periodically monitored for cholecystitis. Cholelithiasis was reported in 2% to 27% of patients with acromegaly treated with lanreotide in pooled data from clinical trials (n = 416); the incidence increased with duration of treatment. In a subset of patients who underwent routine gallbladder ultrasound at baseline, new cholelithiasis was reported in 12% of patients who had gallstones when lanreotide treatment was initiated. The incidence of cholelithiasis was similar in patients with baseline hepatic impairment and those who had normal hepatic function. Cholelithiasis occurred in 14% (grade 3 or 4, 1%) of patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) who received lanreotide; the incidence was similar in lanreotide-treated patients with carcinoid syndrome. Overall, hepatobiliary disorders were reported in 3% to 31% of patients with acromegaly who received lanreotide. If complications of cholelithiasis are suspected, discontinue lanreotide depot and treat appropriately.

An injection site reaction, such as extravasation, granuloma, hematoma, hemorrhage, induration, inflammation, mass/nodule, pain, pruritus, and localized rash, has been reported in 6% to 17% of patients treated with lanreotide in clinical trials (n = 517). Specifically, injection site pain (4%) and injection site mass (2%) were the most frequently reported local adverse reactions in pooled clinical trials of patients with acromegaly. Induration at the injection site occurred in 5% of lanreotide-treated acromegaly patients in a specific analysis. Injection site reactions, usually mild to moderate, were more commonly reported after starting treatment and occurred less frequently as treatment continued. Injection site abscess was reported during postmarketing surveillance.

Lanreotide inhibits the secretion of insulin and glucagon, which may cause either hyperglycemia or hypoglycemia. During clinical studies with lanreotide depot in patients with acromegaly (n = 332), hypoglycemia, diabetes mellitus, or hyperglycemia were reported in 14% of patients, although only 7% of the cases were thought to be secondary to lanreotide. Mild (grade 1 or 2) hyperglycemia was also reported in 14% of patients treated with lanreotide for gastroenteropancreatic tumors (GEP-NET); the incidence was similar in lanreotide-treated patients with carcinoid syndrome. Monitor blood glucose concentrations when lanreotide treatment is initiated or when the dose is altered; adjust any antidiabetic treatment as needed.

Sinus bradycardia (5.5%), bradycardia (2.8%), and hypertension (5.5%) were the most common overall cardiac adverse reactions observed in three pooled lanreotide cardiac studies in patients with acromegaly (n = 217). In one clinical trial, 23% of lanreotide patients (n = 81) with a baseline heart rate of at least 60 beats per minute (bpm) subsequently developed bradycardia (heart rate less than 60 bpm), compared with 16% of those who received placebo (n = 94); only 1% of patients in each group had a documented heart rate less than 50 bpm. In pooled results of 7 clinical trials of patients with acromegaly (n = 416), bradycardia was reported in 3% to 18% of lanreotide-treated patients; heart rate and rhythm disorders were additionally reported in 6% to 21% of patients treated with lanreotide in these trials. Other cardiac adverse reactions occurred in less than 1% of patients; the relationship to lanreotide treatment could not be established because of underlying cardiac disease in many of these patients. Clinically significant (moderate or severe) mitral regurgitation and clinically significant (at least mild) aortic regurgitation has also been reported; however, the incidence is low and is not different from other somatostatin analogs.

During clinical studies evaluating the use of lanreotide depot in acromegaly, arthralgia was reported in 7% to 10% of patients, while musculoskeletal and connective tissue disorders were reported in 17% to 26%. Musculoskeletal pain, including myalgia and back pain, was also reported in 19% (grade 3 or 4, 2%) of patients treated with lanreotide for gastroenteropancreatic neuroendocrine tumor (GEP-NET) compared with 13% (grade 3 or 4, 2%) of those who received placebo. Adverse reactions in patients with carcinoid syndrome were similar to those in the GEP-NET population.

During clinical studies evaluating the use of lanreotide depot, headache was reported in 5% to 7% of patients with acromegaly and 16% of patients being treated for gastroenteropancreatic neuroendocrine tumor (GEP-NET). Nervous system disorders occurred in 19% to 20% of lanreotide-treated patients with acromegaly. Additionally, patients with GEP-NET reported an increased incidence of mild dizziness (9% vs. 2%) and depression (7% vs. 1%) compared with placebo. Adverse reactions in patients with carcinoid syndrome were similar to those in the GEP-NET population.

Anemia was reported in 5% to 14% of acromegaly patients treated with lanreotide in clinical trials (n = 416).

In clinical trials of lanreotide, pancreatitis was reported in less than 1% of patients; it has also been reported in postmarketing experience. Cases of pancreatitis including hemorrhagic and necrotizing pancreatitis have been reported to the FDA, although a causal relationship to lanreotide treatment has not been determined. The FDA will continue to evaluate the potential safety risk associated with these cases. Healthcare providers are encouraged to report any adverse effects associated with lanreotide to the FDA through the MedWatch adverse event reporting program.

Slight decreases in thyroid function have been seen during treatment with lanreotide in acromegalic patients, although clinical hypothyroidism is rare (less than 1%). Thyroid function tests are recommended where clinically indicated. Lanreotide inhibits the nocturnal increase in thyroid-stimulating hormone seen in healthy patients.

In a double-blind, placebo-controlled clinical trial, 6% of patients with gastroenteropancreatic neuroendocrine tumor (GEP-NET) who were treated with lanreotide experienced dyspnea, compared with 1% of those who received placebo. Adverse reactions in patients with carcinoid syndrome were similar to those in the GEP-NET population.

During clinical trials of lanreotide in patients with acromegaly, antibody formation to lanreotide was low (less than 1% to 4% of patients in studies where antibody formation was evaluated). The antibodies did not appear to affect the efficacy or safety of lanreotide. In a double-blind, placebo-controlled clinical trial of patients with gastroenteropancreatic neuroendocrine tumor (GEP-NET), anti-lanreotide antibodies were detected in 4% of patients at 24 weeks, 10% at 48 weeks, 11% at 72 weeks, and 10% at 96 weeks; assessment for neutralizing antibodies was not conducted. In another randomized clinical trial of patients with carcinoid syndrome, less than 2% of those treated with lanreotide developed anti-lanreotide antibodies. The detection of antibody formation is assay-dependent, and may be influenced by several factors including methodology, handling, timing of collection, concomitant medications, and underlying disease; therefore, comparison of the incidence of antibodies to lanreotide with other medications may be misleading.

Angioedema and anaphylaxis/anaphylactoid reactions have been reported with the use of lanreotide in postmarketing experience.

Hypertension occurred in 5% to 7% of patients in pooled clinical trials of lanreotide treatment in patients with acromegaly (n = 416). The incidence was slightly higher (all grade, 14%; severe including hypertensive crisis, 1%) in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs); patients with carcinoid syndrome had similar adverse reactions to patients with GEP-NETs.

Use lanreotide with caution in patients with underlying cardiac disease or preexisting bradycardia. Bradycardia has been reported with lanreotide treatment in clinical trials; appropriate medical management should be initiated in patients with symptomatic bradycardia. In patients without cardiac disease, a decrease in heart rate from lanreotide may not reach the threshold of bradycardia. However, sinus bradycardia may occur in patients with underlying cardiac disorders.

Use lanreotide with caution in patients with preexisting diabetes mellitus, especially when treatment is initiated or when the lanreotide dose is adjusted. Patients receiving antidiabetic medications may need to have their dosages adjusted. Monitor blood glucose levels in all patients. Lanreotide has been shown to inhibit the secretion of insulin and glucagon; therefore, patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Use lanreotide with caution in patients with preexisting gallbladder disease, as it may reduce gallbladder motility and cause or exacerbate gallstone formation. Patients should be periodically monitored. If complications of cholelithiasis are suspected, discontinue lanreotide and treat appropriately.

Use lanreotide with cautions in patients with preexisting hepatic disease. Gastrointestinal disorders, renal disorders, and urinary disorders were more common in patients with documented hepatic impairment in clinical trials.

Use lanreotide with caution in patients with preexisting thyroid disease; thyroid function tests are recommended where clinically indicated. Decreases in thyroid function have occurred during lanreotide therapy, although clinical hypothyroidism is rare.

Use lanreotide with caution in females of reproductive potential. Although there are no adequately controlled studies in pregnant women, decreased embryofetal survival and increased fetal skeletal/soft tissue abnormalities were observed in pregnant rats and rabbits at exposures equivalent to 5-times and 2-times the maximum recommended human dose of 120 mg. Limited data based on postmarketing case reports with lanreotide use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes. Women who are pregnant or who become pregnant while receiving lanreotide should be apprised of the potential hazard to the fetus.

Counsel patients about the reproductive risk during lanreotide treatment. The embryofetal effects of lanreotide during pregnancy are unknown, although decreased embryofetal survival occurred in animal studies. Women who become pregnant while receiving lanreotide should be apprised of the potential hazard to the fetus. Although there are no data regarding the effect of lanreotide on human fertility, female infertility has been observed in animal studies at exposures of approximately 10-fold the plasma exposure at the maximum recommended human dose (120 mg). The fertility of male rats was unaffected by lanreotide at similar exposures.

Due to the potential for serious adverse reactions in nursing infants from lanreotide, including effects on glucose metabolism and bradycardia, advise women to discontinue breast-feeding during treatment and for 6 months after the final dose. It is not known whether lanreotide is present in human milk, although many drugs are excreted in human milk.

For the long-term treatment of acromegaly in patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option:
NOTE: Lanreotide has been designated an orphan drug by the FDA for this indication.
Subcutaneous depot injection dosage (Somatuline Depot):
Adults: Initially, 90 mg via deep subcutaneous injection every 4 weeks for 3 months. After 3 months, adjust dose based on growth hormone (GH) concentration, insulin growth factor-1 (IGF-1), and clinical symptoms. In patients with a GH concentration more than 1 ng/mL but 2.5 ng/mL or less, and clinical symptoms are controlled, continue administering 90 mg subcutaneously every 4 weeks. In patients with a GH concentration more than 2.5 ng/mL, IGF-1 is elevated, and/or clinical symptoms are uncontrolled, increase dose to 120 mg subcutaneously every 4 weeks. In patients with a GH concentration 1 ng/mL or less, IGF-1 is normal, and clinical symptoms are controlled, decrease the dose to 60 mg subcutaneously every 4 weeks. Thereafter, adjust the dose based on patient response, serum GH or IGF-1 concentrations, and/or changes in symptoms of acromegaly. Patients who are controlled on 60 mg or 90 mg may be considered for an extended dosing interval of 120 mg every 6 or 8 weeks. Obtain GH and IGF-1 concentrations 6 weeks after this change in dosing regimen to evaluate persistence of patient response.

For the treatment of unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic malignant neuroendocrine tumor (NET):
NOTE: Lanreotide has been designated an orphan drug by the FDA for this indication.
Subcutaneous depot injection dosage:
Adults: 120 mg by deep subcutaneous injection every 4 weeks. In a multicenter, randomized, double-blind, placebo-controlled clinical trial of patients with unresectable, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (NET), treatment with lanreotide (n = 101) was compared to placebo (n= 103). Lanreotide was associated with a significant improvement in median progression-free survival compared with placebo (not reached at 22 months vs. 16.6 months). In clinical studies of patients with these tumors, symptom reduction is often evident; in patients with flushing as the target symptom, 65% experienced at least a 50% reduction in symptoms, as did 18% of patients with diarrhea as the target symptom.

For the treatment of hyperthyroidism* secondary to thyrotropinoma:
Intramuscular dosage* (long-acting microparticle injection, Somatuline LA, not available in the US)*:
Adults: NOTE: This dosage form is not available in the US. Initially, 30 mg via IM injection once every 14 days; if the therapeutic response is inadequate, as measured by thyroid hormone concentrations and TSH, the dose may be increased to 30 mg every 10 days. In an open label trial, 18 patients with hyperthyroidism secondary to a TSH-secreting pituitary tumor received 30 mg every 14 days for 1 month; after 1 month and based on free T3 concentrations, 7 patients required injections every 10 days while the remainder continued to receive lanreotide every 14 days. Within 1 month, the clinical signs of hyperthyroidism improved; furthermore, by 6 months, both TSH and thyroid hormone concentrations were reduced, with 13 patients achieving concentrations within the normal range.

For the treatment of carcinoid syndrome, to reduce the frequency of short-acting somatostatin analog rescue therapy:
NOTE: Lanreotide has been designated an orphan drug by the FDA for this indication.
Subcutaneous depot injection dosage:
Adults: 120 mg by deep subcutaneous injection every 4 weeks. If patients are already receiving lanreotide for gastroenteropancreatic neuroendocrine tumors (GEP-NETs), do not administer an additional dose for the treatment of carcinoid syndrome. In a multicenter, randomized, double-blind clinical trial, patients treated with lanreotide (n = 59) experienced significantly fewer days on rescue medication compared with patients in the placebo arm (n = 56) (34% vs. 49% of days). Patients treated with lanreotide also had fewer average daily frequencies of diarrhea and flushing events compared with those who received placebo.

For the management of GI bleeding from gastrointestinal angioectasias* in adults:
Subcutaneous depot injection dosage:
Adults: 60 mg to 120 mg subcutaneously every 4 to 6 weeks has been associated with significant improvement in mean hemoglobin. Guidelines recommend somatostatin analogs for red blood cell transfusion-dependent bleeding secondary to GI angioectasias that cannot be adequately controlled with endoscopic therapy; however, octreotide appears to be more effective than lanreotide.

Maximum Dosage Limits:
-Adults
120 mg/dose subcutaneously every 4 weeks.
-Geriatric
120 mg/dose subcutaneously every 4 weeks.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing
Acromegaly:
-Mild hepatic impairment: No dosage adjustment is recommended.
-Moderate to severe hepatic impairment (Child-Pugh Class B or C): Reduce the starting dose to 60 mg by deep subcutaneous injection once every 4 weeks. After 3 months of treatment, adjust the dose based on clinical response.

Patients with Renal Impairment Dosing
Acromegaly:
-CrCL 60 mL/min or higher: No dose adjustment is recommended.
-CrCL less than 59 mL/min: Reduce the starting dose to 60 mg by deep subcutaneous injection once every 4 weeks. After 3 months, adjust the dose based on clinical response. Caution should be exercised when considering these patients for an extended dosing interval (e.g., 120 mg subcutaneously every 6 or 8 weeks).

Neuroendocrine Tumors: It appears that dosage adjustments for renal impairment are not necessary.

*non-FDA-approved indication

Acarbose: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Acebutolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Alogliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Alogliptin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Alogliptin; Pioglitazone: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Amlodipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Amlodipine; Atorvastatin: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Amlodipine; Benazepril: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Amlodipine; Celecoxib: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Amlodipine; Olmesartan: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Amlodipine; Valsartan: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Antidiabetic Agents: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Atenolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Atenolol; Chlorthalidone: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Beta-adrenergic blockers: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Betaxolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Bexagliflozin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Bisoprolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Brimonidine; Timolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Bromocriptine: (Moderate) Monitor for an increase in bromocriptine-related adverse reactions if coadministration with lanreotide is necessary. Limited published data indicate that concomitant administration of a somatostatin analog and bromocriptine may increase the absorption of bromocriptine.

Calcium-channel blockers: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Canagliflozin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Canagliflozin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Carteolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Carvedilol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Clevidipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Cyclosporine: (Moderate) Monitor cyclosporine levels if coadministration of cyclosporine with lanreotide is necessary; adjust the dose of cyclosporine as necessary to maintain therapeutic drug concentrations. Concomitant administration of lanreotide with cyclosporine may decrease the absorption of cyclosporine.

Dapagliflozin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Dapagliflozin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Dextromethorphan; Quinidine: (Major) Monitor ECGs for QT prolongation and watch for an increase in quinidine-related adverse reactions if coadministration with lanreotide is necessary. Quinidine is a CYP3A4 substrate with a narrow therapeutic range. Limited published data available indicate that somatostatin analogs may decrease the metabolic clearance of CYP3A4 substrates, which may be due to the suppression of growth hormone; it cannot be excluded that lanreotide has this effect.

Diltiazem: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Dorzolamide; Timolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Dulaglutide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Empagliflozin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Empagliflozin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Ertugliflozin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Ertugliflozin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Esmolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Exenatide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Felodipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Gallium Ga 68 Dotatate: (Moderate) Image patients with gallium Ga 68 dotatate just prior to dosing with non-radioactive, long-acting somatostatin analogs. Short-acting analogs of somatostatin can be used up to 24 hours before imaging with gallium Ga 68 dotatate. These drugs may competitively bind to the same somatostatin receptors.

Glimepiride: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Glipizide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Glipizide; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Glyburide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Glyburide; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin Aspart: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin Detemir: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin Glargine: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin Glulisine: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin Lispro: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Insulin, Inhaled: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Isophane Insulin (NPH): (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Isradipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Labetalol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Levamlodipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Levobunolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Linagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Linagliptin; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Liraglutide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Lixisenatide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Lutetium Lu 177 dotatate: (Major) Discontinue long-acting lanreotide at least 4 weeks prior to beginning treatment with lutetium Lu 177 dotatate. A short-acting somatostatin analog may be administered as-needed, but must be discontinued at least 24 hours prior to each lutetium Lu 177 dotatate dose. Somatostatin and its analogs, such as lanreotide, competitively bind to somatostatin receptors and may interfere with the efficacy of lutetium Lu 177 dotatate.

Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Metformin; Repaglinide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Metformin; Saxagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Metformin; Sitagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Metoprolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Miglitol: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Nadolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Nateglinide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Nebivolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Nebivolol; Valsartan: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Nicardipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

NIFEdipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Nimodipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Nisoldipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Perindopril; Amlodipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Pindolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Pioglitazone: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Pioglitazone; Glimepiride: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Pioglitazone; Metformin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Pramlintide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Propranolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Quinidine: (Major) Monitor ECGs for QT prolongation and watch for an increase in quinidine-related adverse reactions if coadministration with lanreotide is necessary. Quinidine is a CYP3A4 substrate with a narrow therapeutic range. Limited published data available indicate that somatostatin analogs may decrease the metabolic clearance of CYP3A4 substrates, which may be due to the suppression of growth hormone; it cannot be excluded that lanreotide has this effect.

Regular Insulin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Repaglinide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Rosiglitazone: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Saxagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Semaglutide: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Sitagliptin: (Moderate) Monitor blood glucose levels regularly in patients with diabetes, especially when lanreotide treatment is initiated or when the dose is altered. Adjust treatment with antidiabetic agents as clinically indicated. Lanreotide inhibits the secretion of insulin and glucagon. Patients treated with lanreotide may experience either hypoglycemia or hyperglycemia.

Sotalol: (Moderate) Concomitant administration of bradycardia-inducing drugs such as sotalol may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the dose of sotalol if necessary.

Telmisartan; Amlodipine: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Timolol: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., beta-adrenergic blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the beta-blocker dose if necessary.

Trandolapril; Verapamil: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Verapamil: (Moderate) Concomitant administration of bradycardia-inducing drugs (e.g., calcium-channel blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Adjust the calcium-channel blocker dose if necessary.

Lanreotide is an analog of somatostatin, and is believed to have a mechanism of action similar to that of endogenous somatostatin. Lanreotide has a high affinity for human somatostatin receptors (SSTR) 2 and 5 and a reduced binding affinity for human SSTR 1, 3, and 4. Activity at SSTR 2 and 5 is the primary mechanism believed to be responsible for growth hormone (GH) inhibition. Clinically, lanreotide reduces GH and insulin growth factor-1 (IGF-1) concentrations allowing for normalization of these hormones in patients with acromegaly. Lanreotide reductions in GH are dose-dependent, and the reductions are sustained for at least 28 days after a single injection of the depot formulation. In addition, lanreotide inhibits various endocrine, neuroendocrine, exocrine, and paracrine functions including the basal secretion of motilin, gastric inhibitory peptide, and pancreatic polypeptide as well as inhibition of the postprandial secretion of pancreatic polypeptide, gastrin, and cholecystokinin. Lanreotide also modifies glucose hemostasis; it reduces and delays the secretion of post-prandial insulin secretion, which results in a transient, mild glucose intolerance. In addition, non-significant reductions in glucagon concentrations may occur after lanreotide administration, which temporarily decreases glucose concentrations by 20-30%. Other effects include inhibition of meal-stimulated pancreatic secretions, reduction in duodenal bicarbonate and amylase concentrations, reduction in gastric acidity, inhibition of gallbladder contractility and bile secretion, inhibition of meal-induced increases in superior mesenteric artery and portal venous blood flow, and inhibition of the nocturnal increase in thyroid-stimulating hormone secretion. Finally, long-term lanreotide also decreases prolactin concentrations in patients with acromegaly.

Lanreotide depot is administered via deep subcutaneous injection. Lanreotide depot is thought to form a drug depot at the injection site by interacting with physiological fluids. The most likely mechanism of drug release is a passive diffusion of the precipitated drug from the depot towards the surrounding tissues, followed by absorption into the blood stream. Less than 5% of lanreotide is excreted in the urine and less than 0.5% is recovered unchanged in the feces, indicative of some biliary excretion.

Affected Cytochrome P450 (CYP450) enzymes and drug transporters: CYP3A4
Lanreotide suppresses growth hormone secretion, which may cause a decrease in the metabolic clearance of drugs metabolized by CYP3A4. There is potential for drug-drug interactions with medications that are metabolized by CYP3A4 and also have a narrow therapeutic index.


-Route-Specific Pharmacokinetics
Subcutaneous Route
After a single, deep subcutaneous depot injection, the mean absolute bioavailability in healthy subjects is 73.4%, 69%, and 78.4% for the 60, 90, and 120 mg doses, respectively. Mean Cmax values range from 4.3 to 8.4 ng/mL during the first day in healthy volunteers, and 3.8 +/- 0.5 ng/mL to 7.7 +/- 2.5 ng/mL in patients with acromegaly. Single-dose linearity occurs with respect to AUC and Cmax, although there is high inter-subject variability. Lanreotide depot demonstrates sustained release of lanreotide with a half-life of 23 to 30 days. Mean serum concentrations are greater than 1 ng/mL throughout 28 days after 90 mg and 120 mg injections; mean serum concentrations are greater than 0.9 ng/mL through 28 days after a 60 mg injection. In patients with acromegaly, the accumulation ratio index was 2.7, and the steady state trough concentrations when administered every 28 days were 1.8 +/- 0.3 ng/mL (60 mg), 2.5 +/- 0.9 ng/mL (90 mg), and 3.8 +/- 1 ng/mL (120 mg). A limited initial burst of effect and a low peak-to-trough fluctuation (81% to 108%) of the serum concentration at the plateau were observed. Pharmacokinetic data from studies evaluating extended dosing of lanreotide depot 120 mg demonstrated a mean Cmin of 1.6 ng/mL for the 8-week interval and 2.3 ng/mL for the 6-week interval. Steady state concentrations were reached after 4 to 5 injections in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs), with mean trough concentrations of 5.3 to 8.6 ng/mL.


-Special Populations
Hepatic Impairment
Lanreotide clearance is reduced by 30% when IV immediate-release lanreotide was administered to patients with moderate to severe hepatic impairment. The effect of hepatic impairment on lanreotide clearance in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has not been studied. Lanreotide depot has not been studied in patients with hepatic impairment.

Renal Impairment
Mild to moderate renal impairment (CrCL less than 60 mL/min) does not affect the clearance of lanreotide in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) based on a pharmacokinetic analysis; patients with severe renal impairment (CrCL less than 30 mL/min) were not studied. In subjects with end-stage renal disease requiring dialysis, an approximate 2-fold decrease in total serum clearance of immediate-release lanreotide with an associated 2-fold increase in half-life and AUC occurs. Lanreotide depot has not been studied in acromegaly patients with renal impairment.

Geriatric
Age does not affect the clearance of lanreotide. The half-life and mean residence time of lanreotide were increased by 85% and 65%, respectively, when IV immediate-release lanreotide was administered to elderly patients; the AUC and Cmax were unchanged. Lanreotide depot has not been studied in elderly patients.