LANREOTIDE Drug Interactions: What You Need to Know

INTERACTIONS Cyclosporine : Lanreotide Injection may decrease the absorption of cyclosporine. Dosage adjustment of cyclosporine may be needed. ( 7.2 ) Bromocriptine : Lanreotide Injection may increase the absorption of bromocriptine. ( 7.3 ) Bradycardia-Inducing Drugs (e.g., beta-blockers) : Lanreotide Injection may decrease heart rate. Dosage adjustment of the coadministered drug may be necessary. ( 7.3 )

7.1 Insulin and Oral Hypoglycemic Drugs Lanreotide, like somatostatin and other somatostatin analogs, inhibits the secretion of insulin and glucagon. Therefore, blood glucose levels should be monitored when Lanreotide Injection treatment is initiated or when the dose is altered, and antidiabetic treatment should be adjusted accordingly <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.2 )]</span> .

7.2 Cyclosporine Concomitant administration of cyclosporine with Lanreotide Injection may decrease the absorption of cyclosporine, and therefore, may necessitate adjustment of cyclosporine dose to maintain therapeutic drug concentrations. <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span>

7.3 Bromocriptine Limited published data indicate that concomitant administration of a somatostatin analog and bromocriptine may increase the absorption of bromocriptine <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .

7.4 Bradycardia-Inducing Drugs Concomitant administration of bradycardia-inducing drugs (e.g., beta-blockers) may have an additive effect on the reduction of heart rate associated with lanreotide. Dosage adjustments of concomitant drugs may be necessary.

7.5 Drug Metabolism Interactions The limited published data available indicate that somatostatin analogs may decrease the metabolic clearance of compounds known to be metabolized by cytochrome P450 enzymes, which may be due to the suppression of growth hormone. Since it cannot be excluded that Lanreotide Injection may have this effect, avoid other drugs mainly metabolized by CYP3A4 and which have a low therapeutic index (e.g., quinidine, terfenadine). Drugs metabolized by the liver may be metabolized more slowly during Lanreotide Injection treatment and dose reductions of the concomitantly administered medications should be considered <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.3 )]</span> .

Lanreotide Injection is contraindicated in patients with history of a hypersensitivity to lanreotide. Allergic reactions (including angioedema and anaphylaxis) have been reported following administration of lanreotide [ see Adverse Reactions ( 6.3 )] . Hypersensitivity to lanreotide. ( 4 )

AND PRECAUTIONS Cholelithiasis and Complications of Cholelithiasis: Monitor periodically. Discontinue if complications of cholelithiasis are suspected. Gallstones may occur; consider periodic monitoring. ( 5.1 ) Hyperglycemia and Hypoglycemia: Glucose monitoring is recommended and antidiabetic treatment adjusted accordingly. ( 5.2 , 7.1 )

Cardiovascular

Abnormalities: Decrease in heart rate may occur. Use with caution in at-risk patients. ( 5.3 )

Thyroid Function

Abnormalities: Decreases in thyroid function may occur; perform tests where clinically indicated. ( 5.4 ) Steatorrhea and Malabsorption of Dietary Fats: New onset steatorrhea, stool discoloration, loose stools, abdominal bloating, and weight loss may occur. If new occurrence or worsening of these symptoms are reported, evaluate for potential pancreatic exocrine insufficiency. ( 5.6 )

5.1 Cholelithiasis and Complications of Cholelithiasis Lanreotide Injection may reduce gallbladder motility and lead to gallstone formation; therefore, patients may need to be monitored periodically <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.2 )]</span> . There have been postmarketing reports of cholelithiasis (gallstones) resulting in complications, including cholecystitis, cholangitis, and pancreatitis, and requiring cholecystectomy in patients taking Lanreotide Injection. If complications of cholelithiasis are suspected, discontinue Lanreotide Injection and treat appropriately.

5.2 Hyperglycemia and Hypoglycemia Pharmacological studies in animals and humans show that lanreotide, like somatostatin and other somatostatin analogs, inhibits the secretion of insulin and glucagon. Hence, patients treated with Lanreotide Injection may experience hypoglycemia or hyperglycemia. Blood glucose levels should be monitored when lanreotide treatment is initiated, or when the dose is altered, and antidiabetic treatment should be adjusted accordingly <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>.

5.3 Cardiovascular Abnormalities The most common overall cardiac adverse reactions observed in three pooled Lanreotide Injection cardiac studies in patients with acromegaly were sinus bradycardia (12/217, 5.5%), bradycardia (6/217, 2.8%), and hypertension (12/217, 5.5%) <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>.

In

81 patients with baseline heart rates of 60 beats per minute (bpm) or greater treated with Lanreotide Injection in Study 3, the incidence of heart rate less than 60 bpm was 23% (19/81) as compared to 16% (15/94) of placebo treated patients; 10 patients (12%) had documented heart rates less than 60 bpm on more than one visit. The incidence of documented episodes of heart rate less than 50 bpm as well as the incidence of bradycardia reported as an adverse event was 1% in each treatment group. Initiate appropriate medical management in patients who develop symptomatic bradycardia. In patients without underlying cardiac disease, Lanreotide Injection may lead to a decrease in heart rate without necessarily reaching the threshold of bradycardia. In patients suffering from cardiac disorders prior to Lanreotide Injection treatment, sinus bradycardia may occur. Care should be taken when initiating treatment with Lanreotide Injection in patients with bradycardia.

5.4 Thyroid Function Abnormalities Slight decreases in thyroid function have been seen during treatment with lanreotide in acromegalic patients, though clinical hypothyroidism is rare (less than 1%). Thyroid function tests are recommended where clinically indicated.

5.5 Monitoring: Laboratory Tests Acromegaly: Serum GH and IGF-1 levels are useful markers of the disease and the effectiveness of treatment <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 )]</span>.

5.6 Steatorrhea and Malabsorption of Dietary Fats New onset steatorrhea, stool discoloration and loose stools have been reported in patients receiving somatostatin analogs, including lanreotide injection. Somatostatin analogs reversibly inhibit secretion of pancreatic enzymes and bile acids, which may result in malabsorption of dietary fats and subsequent symptoms of steatorrhea, loose stools, abdominal bloating, and weight loss. If new occurrence or worsening of these symptoms are reported in patients receiving Lanreotide Injection, evaluate patients for potential pancreatic exocrine insufficiency and manage accordingly.