Somatuline Depot

Appropriate studies have not been performed on the relationship of age to the effects of lanreotide injection in the pediatric population. Safety and efficacy have not been established.

Somatuline Depot may cause serious side effects, including:

• gallstones. Tell your doctor if you have any of these symptoms:
  • sudden pain in your upper right stomach area (abdomen)
  • sudden pain in your right shoulder or between your shoulder blades
  • yellowing of your skin and whites of your eyes
  • fever with chills
  • nausea
• changes in your blood sugar (high blood sugar or low blood sugar). If you have diabetes, test your blood sugar as your doctor tells you to. Your doctor may change your dose of diabetes medicine especially when you first start receiving injections or if your dose changes.
• slow heart rate
• high blood pressure

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• slow heart rate;

• dangerously high blood pressure--severe headache, blurred vision, pounding in your neck or ears, nosebleed, anxiety;

• low blood sugar--headache, hunger, weakness, sweating, confusion, irritability, dizziness, fast heart rate, or feeling jittery;

• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss; or

• signs of a gallbladder problem--sudden severe pain in your upper stomach spreading to your back or shoulder (may occur after meals or at night), pain when breathing, nausea, vomiting, loss of appetite, fever, chills, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• nausea, vomiting, stomach pain;

• diarrhea, gas; or

• pain, itching, or a hard lump where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Synthetic octapeptide pharmacologically related to somatostatin.1 6 8

Acromegaly

Long-term treatment of acromegaly in patients who have had inadequate responses to or are not candidates for surgical resection and/or radiotherapy (designated an orphan drug by FDA for this use).1 2

Goal of therapy is to normalize concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1).1

Improves certain manifestations of acromegaly (asthenia, joint pain, swelling of extremities, excessive perspiration, headache).4

General

• Individualize dosage based on patient’s response (GH and IGF-1 levels, clinical symptoms); monitor serum GH and IGF-1 concentrations and adjust dosage accordingly.1 9

Administration

Sub-Q Administration

Administer by deep sub-Q injection into the upper outer quadrant of the buttock; alternate injection sites every 4 weeks between the right and left buttock.1 5

Allow product to reach room temperature by removing sealed pouch from refrigerator 30 minutes prior to administration.1 Keep pouch sealed until time of administration.1

Insert the needle rapidly to its full length at an angle perpendicular to the skin; the skin should not be folded prior to administration.1

Dosage

Available as lanreotide acetate; dosage expressed in terms of lanreotide.1

Adults

Initially, 90 mg once every 4 weeks for 3 months.1

After 3 months, adjust subsequent dosages based on response (GH and IGF-1 concentrations and clinical response) (see Table 1).1

Special Populations

Hepatic Impairment

In patients with moderate to severe hepatic impairment, initially, 60 mg once every 4 weeks for 3 months.1 Subsequent dosages are determined based on GH and IGF-1 concentrations and clinical response.1

Renal Impairment

In patients with moderate to severe hepatic impairment, initially, 60 mg once every 4 weeks for 3 months.1 Subsequent dosages are determined based on GH and IGF-1 concentrations and clinical response.1

Geriatric Patients

Dosage adjustments not required.1

Use Somatuline Depot as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into the fatty part of the skin.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of gallstones like sudden pain in the upper right belly area, right shoulder area, or between the shoulder blades; yellow skin or eyes; or fever with chills.
• Very upset stomach or throwing up.
• Very bad belly pain.
• Very bad dizziness or passing out.
• Very bad headache.
• Slow heartbeat.
• A heartbeat that does not feel normal.
• Feeling very tired or weak.
• Low mood (depression).
• Shortness of breath.
• Low blood sugar may occur. Signs may be dizziness, headache, feeling sleepy, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating. Call the doctor right away if any of these signs occur. Follow what you have been told to do if low blood sugar occurs. This may include taking glucose tablets, liquid glucose, or some fruit juices.

Pregnancy

Pregnancy Category C

Lanreotide has been shown to have an embryocidal effect in rats and rabbits. There are no adequate and well-controlled studies in pregnant women. Somatuline Depot should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Reproductive studies in pregnant rats given 30 mg/kg by subcutaneous injection every 2 weeks (five times the human dose, based on body surface area comparisons) resulted in decreased embryo/fetal survival. Studies in pregnant rabbits given subcutaneous injections of 0.45 mg/kg/day (two times the human therapeutic exposures at the maximum recommended dose of 120 mg, based on comparisons of relative body surface area) shows decreased fetal survival and increased fetal skeletal/soft tissue abnormalities.

Nursing Mothers

It is not known whether lanreotide is excreted in human milk. Many drugs are excreted in human milk. As a result of serious adverse reactions from Somatuline Depot in animals and, potentially in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, after taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

No overall differences in safety or effectiveness were observed between elderly patients with acromegaly compared with younger patients and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Study 3, conducted in patients with GEP-NET, did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Acromegaly

It is not necessary to alter the starting dose in elderly patients; lanreotide serum concentrations in the elderly are well within the range of serum concentrations safely tolerated in healthy young subjects. Similarly, it is not necessary to alter the titration or maintenance doses of Somatuline Depot, as dose selection is based on therapeutic response [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].

Gastroenteropancreatic Neuroendocrine Tumors

No dose adjustment required. [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

Renal Impairment

Acromegaly

Lanreotide has been studied in patients with end-stage renal function on dialysis, but has not been studied in patients with mild, moderate, or severe renal impairment. It is recommended that patients with moderate or severe renal impairment receive a starting dose of lanreotide of 60 mg. Caution should be exercised when considering patients with moderate or severe renal impairment for an extended dosing interval of Somatuline Depot 120 mg every 6 or 8 weeks [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].

Gastroenteropancreatic Neuroendocrine Tumors

No effect was observed in total clearance of lanreotide in patients with mild to moderate renal impairment receiving Somatuline Depot 120 mg. Patients with severe renal impairment were not studied [see (Clinical Pharmacology (12.3)].

Hepatic Impairment

Acromegaly

It is recommended that patients with moderate or severe hepatic impairment receive a starting dose of lanreotide of 60 mg. Caution should be exercised when considering patients with moderate or severe hepatic impairment for an extended dosing interval of Somatuline Depot 120 mg every 6 or 8 weeks [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].

Gastroenteropancreatic Neuroendocrine Tumors

Somatuline Depot has not been studied in patients with hepatic impairment.

Somatuline Depot (lanreotide) Injection 60 mg/0.2 mL, 90 mg/0.3 mL, and 120 mg/0.5 mL is a prolonged-release formulation for deep subcutaneous injection. It contains the drug substance lanreotide acetate, a synthetic octapeptide with a biological activity similar to naturally occurring somatostatin, water for injection and acetic acid (for pH adjustment).

Somatuline Depot is available as sterile, ready-to-use, single-use prefilled syringes containing lanreotide acetate supersaturated bulk solution of 24.6% w/w lanreotide base.

Lanreotide acetate is a synthetic cyclical octapeptide analog of the natural hormone, somatostatin. Lanreotide acetate is chemically known as [cyclo S-S]-3-(2-naphthyl)-D-alanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-valyl-L-cysteinyl-L-threoninamide, acetate salt. Its molecular weight is 1096.34 (base) and its amino acid sequence is:

For appearance of the formulation, see Dosage Forms and Strengths (3).

Carcinogenicity, Mutagenicity, Impairment of Fertility

Standard lifetime carcinogenicity bioassays were conducted in mice and rats. Mice were given daily subcutaneous doses of lanreotide acetate at 0.5, 1.5, 5, 10 and 30 mg/kg for 104 weeks. Cutaneous and subcutaneous tumors of fibrous connective tissues at the injection sites were observed at the high dose of 30 mg/kg/day. Fibrosarcomas in both genders and malignant fibrous histiocytomas were observed in males at 30 mg/kg/day resulting in exposures 3-times higher than the clinical therapeutic exposure at the maximum therapeutic dose of 120 mg given by monthly subcutaneous injection based on the AUC values. Rats were given daily subcutaneous doses of lanreotide acetate at 0.1, 0.2, and 0.5 mg/kg for 104 weeks. Increased cutaneous and subcutaneous tumors of fibrous connective tissues at the injection sites were observed at the dose of 0.5 mg/kg/day resulting in exposures less than the clinical therapeutic exposure at 120 mg given by monthly subcutaneous injection. The increased incidence of injection site tumors in rodents is likely related to the increased dosing frequency (daily) in animals compared to monthly dosing in humans and therefore may not be clinically relevant.

Lanreotide was not genotoxic in tests for gene mutations in a bacterial mutagenicity (Ames) assay, or mouse lymphoma cell assay with or without metabolic activation. Lanreotide was not genotoxic in tests for the detection of chromosomal aberrations in a human lymphocyte and in vivo mouse micronucleus assay.

Subcutaneous dosing (30mg/kg/2 wks) before mating and continuing into gestation in rats at doses five times the human clinical exposure (120 mg every 4 weeks) based on mg/m2 had reduced fertility. Gestation length was statistically significantly increased suggesting some delay in parturition at three times the human exposure. The reduction in fertility in non-acromegalic animals is likely related to the pharmacologic activity (decreased growth hormone secretion) of lanreotide acetate.

Somatuline Depot (lanreotide) is a man-made protein that is similar to a hormone in the body called somatostatin. Lanreotide lowers many substances in the body such as insulin and glucagon (involved in regulating blood sugar), growth hormone, and chemicals that affect digestion.

Somatuline Depot is used to treat acromegaly in people who cannot be treated with surgery or radiation.

Somatuline Depot is also used to treat a certain type of tumor that starts in the pancreas or digestive tract and may spread to other parts of the body.

Somatuline Depot is sometimes given when surgery or radiation have been tried without success.

Somatuline Depot can make it harder for your body to absorb other medicines you take by mouth. Ask your doctor about the best schedule for taking all of your needed medicines.

Your doctor will determine a dosage that’s right for you based on your individual needs. Your general health may affect your dosage. Tell your doctor about all health conditions you have before your healthcare provider administers Somatuline Depot to you.

You’ll receive this drug once every 4 weeks

How long does it take?

Can I drive home after?

Clinical monitoring

Insurance

Show Sources

• Ipsen Pharmaceuticals. (2014, December). Somatuline Depot (lanreotide) injection [package insert]. Basking Ridge, NJ. Retrieved from http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022074s011lbl.pdf
• National Institute of Diabetes and Digestive and Kidney Diseases. (2012, April). Acromegaly. Retrieved from http://www.niddk.nih.gov/health-information/health-topics/endocrine/acromegaly/Pages/fact-sheet.aspx

Content developed in collaboration with University of Illinois-Chicago, Drug Information Group

Medically reviewed by Creighton University, Center for Drug Information and Evidence-Based Practice on May 12, 2016