Adverse Reaction | Somatuline® Depot 120mg Injection

SAFETY

ESTABLISHED SAFETY PROFILE

Somatuline^® Depot safety profile in patients with GEP-NETs vs placebo^1,2

CLARINET^1,2

ADVERSE REACTIONS OCCURRING IN ≥5% OF SOMATULINE DEPOT-TREATED PATIENTS AND AT A HIGHER RATE THAN
PLACEBO-TREATED PATIENTS¹

	Somatuline Depot 120 mg (n=101)		Placebo (n=103)
	Any (%)	Severe^† (%)	Any (%)	Severe^† (%)
Any Adverse Reactions	88	26	90	31
Abdominal Pain^a	34*	6*	24*	4
Musculoskeletal Pain^b	19*	2*	13	2
Vomiting	19*	2*	9*	2*
Headache	16	0	11	1
Injection Site Reaction^c	15	0	7	0
Hyperglycemia^d	14*	0	5	0
Hypertension^e	14*	1*	5	0
Cholelithiasis	14*	1*	7	0
Dizziness	9	0	2*	0
Depression^f	7	0	1	0
Dyspnea	6	0	1	0

Adverse reactions observed during the first weeks of treatment were mild and transient²

Rates of discontinuation due to treatment-emergent adverse reactions were 5% with Somatuline Depot vs 3% with placebo
Most common adverse reaction was diarrhea for both Somatuline Depot and placebo (35%)

Rates of discontinuation due to treatment-emergent adverse reactions were similar to those observed with placebo¹

^aIncludes preferred terms of abdominal pain, abdominal pain upper/lower, abdominal discomfort.

^bIncludes preferred terms of myalgia, musculoskeletal discomfort, musculoskeletal pain, back pain.

^cIncludes preferred terms of infusion site extravasation, injection site discomfort, injection site granuloma, injection site hematoma, injection site hemorrhage, injection site induration, injection site mass, injection site nodule, injection site pain, injection site pruritus, injection site rash, injection site reaction, injection site swelling.

^dIncludes preferred terms of diabetes mellitus, glucose tolerance impaired, hyperglycemia, type 2 diabetes mellitus.

^eIncludes preferred terms of hypertension, hypertensive crisis.

^fIncludes preferred terms of depression, depressed mood.

^*Includes one or more serious adverse events (SAEs) defined as any event that results in death, is life-threatening, results in hospitalization or prolongation of hospitalization, results in persistent or significant disability, results

in congenital anomaly/birth defect, or may jeopardize the patient, and may require medical or surgical intervention to prevent one of the outcomes listed.

^†Defined as hazardous to well-being, significant impairment of function, or incapacitation.

ELECT^1,3

Adverse reactions reported in the ELECT study¹:

Generally similar to those observed in the CLARINET clinical study
Adverse events occurring by Week 16 in ELECT in ≥5% of Somatuline Depot-treated patients and occurring at least 5% more than in placebo-treated patients were headache (12% vs 5%), dizziness (7% vs 0%), and muscle spasm (5% vs 0%)

GEP-NET=gastroenteropancreatic neuroendocrine tumor; SAE=serious adverse event.

REFERENCES:

Somatuline Depot (lanreotide) Injection [Prescribing Information]. Cambridge, MA: Ipsen Biopharmaceuticals, Inc.; February 2023.
Caplin ME, Pavel M, Ćwikła JB, et al.; on behalf of the CLARINET Investigators. Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med. 2014;371(3):224-233.
Vinik AI, Wolin EM, Liyanage N, et al.; on behalf of the ELECT Study Group. Evaluation of lanreotide depot/autogel efficacy and safety as a carcinoid syndrome treatment (ELECT): a randomized, double-blind, placebo-controlled trial. Endocr Pract. 2016;22(9):1068-1080.

IMPORTANT SAFETY INFORMATION & INDICATIONS

Contraindications

SOMATULINE DEPOT is contraindicated in patients with hypersensitivity to lanreotide. Allergic reactions (including angioedema and anaphylaxis) have been reported following administration of lanreotide.

Warnings and Precautions

Cholelithiasis and Gallbladder Sludge

SOMATULINE DEPOT may reduce gallbladder motility and lead to gallstone formation.
Periodic monitoring may be needed.
If complications of cholelithiasis are suspected, discontinue SOMATULINE DEPOT and treat appropriately.

Hypoglycemia or Hyperglycemia

Patients treated with SOMATULINE DEPOT may experience hypoglycemia or hyperglycemia.
Blood glucose levels should be monitored when SOMATULINE DEPOT treatment is initiated, or when the dose is altered, and antidiabetic treatment should be adjusted accordingly.

Cardiovascular Abnormalities

SOMATULINE DEPOT may decrease heart rate.
In patients without underlying cardiac disease, SOMATULINE DEPOT may lead to a decrease in heart rate without necessarily reaching the threshold of bradycardia.
In patients suffering from cardiac disorders prior to treatment, sinus bradycardia may occur. Care should be taken when initiating treatment in patients with bradycardia.

Most Common Adverse Reactions

GEP-NETs: Adverse reactions in >10% of patients who received SOMATULINE DEPOT were abdominal pain (34%), musculoskeletal pain (19%), vomiting (19%), headache (16%), injection site reaction (15%), hyperglycemia (14%), hypertension (14%), and cholelithiasis (14%).

Carcinoid Syndrome: Adverse reactions occurring in the carcinoid syndrome trial were generally similar to those in the GEP-NET trial. Adverse reactions in ≥5% of patients who received SOMATULINE DEPOT and at least 5% greater than placebo were headache (12%), dizziness (7%) and muscle spasm (5%).

Drug Interactions

SOMATULINE DEPOT may decrease the absorption of cyclosporine (dosage adjustment may be needed); increase the absorption of bromocriptine; and require dosage adjustment for bradycardia-inducing drugs (e.g., beta-blockers).

Special Populations

Lactation: Advise women not to breastfeed during treatment and for 6 months after the last dose.

INDICATIONS

SOMATULINE^® DEPOT (lanreotide) is a somatostatin analog indicated for: the treatment of adult patients with unresectable, well- or moderately-differentiated, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) to improve progression-free survival; and

the treatment of adults with carcinoid syndrome; when used, it reduces the frequency of short-acting somatostatin analog rescue therapy.