SOMATULINE LP

Lanreotide is a drug employed in the management of acromegaly (a hormonal condition caused by excess growth hormone) in addition to symptoms caused by neuroendocrine tumors, especially carcinoid syndrome.

This drug is a long-acting analog of the drug somatostatin, a growth hormone inhibitor.

Lanreotide is

It is approved in several countries worldwide, including the United Kingdom, Australia, and Canada.

Lanreotide was first approved for use in the United States by the FDA on August 30, 2007.

Lanreotide is indicated for the long-term treatment of patients with acromegaly who have had an inadequate response to, or cannot be treated with, surgery and/or radiotherapy.

It is also indicated in 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.

Lanreotide is additionally indicated for the treatment of adults with carcinoid syndrome.

• when used, it reduces the frequency of short-acting somatostatin analog rescue therapy.

Lanreotide exhibits antisecretory effects through cAMP suppression, and activation of ion currents such as K+ and Ca2+ which leads to hyperpolarization of the membrane and inhibition of Ca2+ mediated depolarization.

Furthermore, through direct and indirect mechanisms, Lanreotide has potent antiproliferative effects.

Somatostatin receptor type 2 Agonist Somatostatin receptor type 5 Agonist.

Lanreotide forms a drug depot at the site of injection; therefore, there are 2 phases that describe the absorption of Lanreotide: Initial rapid subcutaneous release during the first few days of treatment where drug that has not precipitated is rapidly absorbed. 2.

Slow release of drug from the depot via passive diffusion.

Absorption is independent of body weight, gender, and dosage.

<5% of lanreotide is excreted in urine, and less than 0.5% is excreted unchanged in the feces suggesting biliary excretion involvement.

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The most common adverse events are

GI related, occurring in 67-84% of patients, and are typically mild to moderate.

GI related effects are often transient, improve with subsequent injections, and most frequently include diarrhea and abdominal pain.

GI symptoms such as nausea, vomiting, and abdominal distension are less common.

It is not clear whether or not GI effects are dose related.

Adverse effects relating to site of injection occur in 43% of patients and are more common in patients who self-inject as opposed to those who had health-care professionals administer the injection.

A small number of patients report newly impaired glucose tolerance, fasting glucose or diabetes mellitus.

Patients being treated for diabetes mellitus may experience hypoglycemia.

After 1 year, up to 30% of patients may experience gallstone formation and the presence of sludge within the gallbladder due to inhibition of gallbladder and GI motility.

This may be influenced by previous exposure to somatostatin analogues.

Other adverse effects include reduction in left ventricular end-diastolic and end-systolic volumes, bradycardia, nasopharyngitis, and alopecia.

Lanreotide is classified as Pregnancy Category

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.

Hypersensitivity to lanreotide.

For deep subcutaneous injection only.

Intended for administration by a healthcare provider.

Administer in the superior external quadrant of the buttock.

Alternate injection sites.

Acromegaly: 90 mg every 4 weeks for 3 months.

Adjust thereafter based on

GH and/or IGF-1 levels.

See full prescribing information for titration regimen.

GEP-NETs: 120 mg every 4 weeks.

Syndrome: 120 mg every 4 weeks.

If patients are already being treated with Lanreotide Injection for GEP-NET, do not administer an additional dose for carcinoid syndrome.

See full prescribing information for dosage adjustment in patients with acromegaly and renal or hepatic impairment. 2.1 Recommended Dosage Acromegaly The recommended starting dosage of Lanreotide Injection is 90 mg given via the deep subcutaneous route, at 4-week intervals for 3 months.

After 3 months, the Lanreotide injection dosage may be adjusted as follows: GH greater than 1 ng/mL to less than or equal to 2.5 ng/mL, IGF-1 normal, and clinical symptoms controlled: maintain dosage at 90 mg every 4 weeks.

GH greater than 2.5 ng/mL, IGF-1 elevated, and/or clinical symptoms uncontrolled: increase dosage to 120 mg every 4 weeks.

GH less than or equal to 1 ng/mL, IGF-1 normal, and clinical symptoms controlled: reduce dosage to 60 mg every 4 weeks.

Thereafter, the dosage should be adjusted according to the response of the patient as judged by a reduction in serum GH and/or IGF-1 levels; and/or changes in symptoms of acromegaly.

Patients who are controlled on Lanreotide

Injection 60 or 90 mg may be considered for an extended dosing interval of Lanreotide Injection 120 mg every 6 or 8 weeks.

GH and

IGF-1 levels should be obtained 6 weeks after this change in dosing regimen to evaluate persistence of patient response.

Continued monitoring of patient response with dosage adjustments for biochemical and clinical symptom control, as necessary, is recommended.

Tumors (GEP-NETs) The recommended dosage of Lanreotide Injection is 120 mg administered every 4 weeks by deep subcutaneous injection.

Carcinoid Syndrome The recommended dosage of Lanreotide Injection is 120 mg administered every 4 weeks by deep subcutaneous injection.

If patients are already being treated with Lanreotide Injection for GEP-NETs, do not administer an additional dose for the treatment of carcinoid syndrome. 2.2 Dosage Adjustment in Renal Impairment Acromegaly The recommended starting dosage of Lanreotide Injection in acromegalic patients with moderate or severe renal impairment (creatinine clearance (CLcr) less than 60 mL/min) is 60 mg via the deep subcutaneous route at 4-week intervals for 3 months followed by dosage adjustment. 2.3 Dosage Adjustment in Hepatic Impairment Acromegaly The recommended starting dosage of Lanreotide Injection in acromegalic patients with moderate or severe hepatic impairment (Child-Pugh Class B or C) is 60 mg via the deep subcutaneous route at 4-week intervals for 3 months followed by dosage adjustment. 2.4 Important Preparation and Administration Instructions The following instructions explain how to inject Lanreotide Injection: Read all instructions carefully before starting the injection.

Follow this procedure exactly, as it may differ from your past experience.

This is a single-dose pre-filled syringe with a single-use safety needle with a green needle shield (that cannot be removed) in a clear needle cap.

ALL the medication must be injected

SLOWLY over 20 seconds during the use.

If you drop or damage the device in any way, please call 1-866-604-3268.

Figure The box includes the following items: Sterile needle pack containing Sterile needle Sterile Laminated pouch with sterile syringe pre-filled with LANREOTIDE INJECTION Instructions for Use Leaflet Prescribing Information Leaflet CAUTION NEVER TOUCH OR TRY TO OPEN THE GREEN NEEDLE SHIELD throughout the course of operation of the device.

Green needle shield is

NOT a removable cap or cover for the needle.

Green needle shield will automatically activate once the injection is complete.

Green needle shield is a self-operating safety lock mechanism.

Needle is fully covered by green needle shield.

Needle is visible only through a small window in the green needle shield.

Inject medication slowly over 20 seconds.

DO NOT rush the injection.

Remove box from refrigerator 30 minutes prior to injecting.

Product left in its sealed pouch at room temperature (not to exceed 104°F or 40°C) for up to 72 hours may be returned to the refrigerator for continued storage and usage at a later time.

Stretch out the skin around injection site to make it flat and tight using your thumb and index finger.

DO NOT pinch the skin around injection site.

A. BEFORE YOU START Figure 2 A1.

INJECTION from the refrigerator 30 minutes prior to injecting (Figure 2).

Do not open the sterile pouch yet.

Product left in its sealed pouch at room temperature (not to exceed 104° F or 40 °C) for up to 72 hours may be returned to the refrigerator for continued storage and use at a later time.

Figure 3 A2.

Wash your hands with soap and dry your hands thoroughly before starting (Figure 3).

Follow the doctor or institution’s policy on the use of surgical gloves during the procedure Figure 4 A3.

Before opening the sterile pouch, confirm that it is intact, and that the medication has not expired.

Syringe is sterile only if the pouch is sealed and undamaged.

Do not use if the pouch is opened, tampered with or damaged.

The expiry date is printed on the outer carton and the pouch.

• Do not use if the medication has expired. (Figure 4).

Or Figure 5 A4.

Make sure there is a clean surface for preparation.

Find a clean, comfortable area for the patient to relax during procedure (Figure 5).

It's important that the patient remains as still as possible during the injection.

Figure 6 A5.

Choose injection site.

• the sites are upper outer areas of the buttock as shown below It is very important that you only inject in one of the areas marked OK in the picture (Figure 6).

Alternate the injection site between the right and left side each time an injection of LANREOTIDE INJECTION is administered.

Figure 7 A6.

Prepare the injection site by cleaning it with alcohol wipes (Figure 7) .

Figure 8 A7.

Tear open the sterile pouch and take out the sterile pre-filled syringe (Figure 8).

B. PREPARE THE SYRINGE Figure 9 B1: Open the sterile needle cap (Figure 9) The needle is sterile only if the needle cap is sealed and undamaged.

Do not use if the needle cap is opened, tampered with or damaged.

Hold the clear needle cap and pull the lid off.

DO NOT TOUCH THE OPEN END OF THE NEEDLE CAP TO MAINTAIN STERILITY.

Figure 10 B2: Remove the cap from the sterile syringe (Figure 10) With one hand, hold the syringe barrel steady (not the plunger ).

With the other hand, remove the cap by twisting it.

B3: Prepare the assembly (Figure 11) Figure 11 Hold the needle cap with one hand and the syringe barrel ( not the plunger ) with the other Carefully insert the open end of the syringe into the open end of the needle cap Twist the syringe barrel clockwise until it is tight to make sure that the syringe is well connected to the safety needle.

DEVICE (SYRINGE AND NEEDLE) ARE COMPLETELY CONNECTED.

The assembly is fully locked when you cannot turn it any further.

B4: Remove the needle from the needle cap Figure 12 Hold the syringe barrel ( not the plunger ).

Pull the needle straight out from the needle cap without twisting or turning (Figure 12).

Figure 13 CAUTION: NEVER TOUCH THE GREEN NEEDLE SHIELD.

THERE IS A RISK OF NEEDLE STICK INJURY. (Figure 13) Green needle shield is a self-operating safety lock mechanism and is not a removable cover or cap for the needle.

It will activate once the injection is complete.

The needle is fully covered by the green shield and is visible only through the small round window at the end of the shield.

C.PERFORM INJECTION C1: Position the syringe assembly Figure 14 Stretch out the skin around the injection site to make it flat and tight using your thumb and index finger. (Figure 14) Figure 15 DO NOT pinch the skin (Figure 15) Figure 16 Hold the assembly by the lower part of the syringe barrel ( not the plunger ) with your other hand.

Position the syringe assembly at a 90-degree angle to the skin.

The green collar at the bottom of the green shield should be perpendicular to the injection site (Figures and 17) Figure 17 C2: Insert the needle (Figure 18) Figure 18 Holding the skin flat and tight, push the syringe assembly firmly into the skin.

Do NOT pinch the skin.

Keep pushing until you reach a “hard stop” and only the green collar at the end of the green needle shield remains visible.

Do NOT push the plunger yet.

DO NOT aspirate.

Keep pressing against the skin.

During this step you should not see the needle.

C3: Push the top of the plunger (Figure 19) Figure 19 Keep holding your hand on the syringe barrel to maintain a 90-degree angle throughout the injection.

While keeping the syringe pressed against the skin, slowly press down the plunger.

You may want to use both hands while applying pressure during the injection of drug.

Continue slowly pushing the plunger over 20 seconds until the Plunger top touches the syringe end.

The medication is thicker and harder to push than you might expect.

Pushing the plunger too fast may cause discomfort to the patient.

While depressing the plunger, slowly count to and CONTINUE STEADY PRESSURE on the plunger.

You may find it helpful to say: a “1 one-thousand” b “2 one-thousand” c “3 one-thousand” up to “20 one-thousand” During this step, as the needle is lowering, the green needle shield will retract.

You should only see the green collar of the green needle shield.

D. REMOVE AND THROW AWAY THE SYRINGE ASSEMBLY Figure 20 D1: Remove from the skin (Figure 20) Lift the syringe straight up and away from the body.

The green needle shield will return to its original position and will fully cover the needle.

Figure 21 D2: Apply gentle pressure (Figure 21) Apply gentle pressure to the injection site with a dry cotton ball or sterile gauze to prevent any bleeding.

Do NOT rub or massage the injection site after administration.

Figure 22 D3: Check needle (Figure 22) Check through the green needle shield’s round windows that the needle was not damaged during administration.

If any damage or malfunction to the needle is suspected please contact 1-866-604-3268 Figure 23 D4: Throw away / Disposal (Figure 23) DO NOT remove needle from syringe Dispose of complete product in sharps disposal container Do not dispose of the syringe or needle in the regular trash.

The syringe and needle are not reusable. fig 1 fig 2 fig 3 fig 4 fig 5 fig 6 fig 7 fig 8 fig 9 fig 10 fig 11 fig 12 fig 13 fig 14 fig 15 fig 16 fig 17 fig 18 fig 19 fig 20 fig 21 fig 22 fig 23 fig 24 fig 25 fig 26 fig 27 fig 28 Fig 29.

Injection is supplied in strengths of 60 mg/0.2 mL, 90 mg/0.3 mL, and 120 mg/0.5 mL lanreotide as a white to pale yellow, semi-solid formulation in a single-dose, sterile, prefilled, ready-to-use, polypropylene syringe and a safety needle device.

The safety needle device is a sterile, single use needle system consisting of a needle (1.2 mm x 20 mm, stainless steel) held in protective plastic safety housing.

The single-dose prefilled syringe is contained in a plastic tray and is packed in a triple-layered aluminium pouch.

The sterile safety needle is co-packaged along with the sealed aluminium pouch in the kit carton box and is attached to the former at the point of use.

NDC 69097-880-67 60 mg/0.2 mL lanreotide, sterile, prefilled syringe NDC 69097-890-67 90 mg/0.3 mL lanreotide, sterile, prefilled syringe NDC 69097-870-67 120 mg/0.5 mL lanreotide, sterile, prefilled syringe Storage and Handling Store Lanreotide Injection in the refrigerator at 2°C to 8°C (36°F to 46°F).

Protect from light.

Store in the original package.

Product left in its sealed pouch at room temperature (not to exceed 104°F or 40°C) for up to 72 hours may be returned to the refrigerator for continued storage and usage at a later time.

Limited available data based on post-marketing case reports with lanreotide use in pregnant women are not sufficient to determine a drug-associated risk of adverse developmental outcomes.

In animal reproduction studies, decreased embryo/fetal survival was observed in pregnant rats and rabbits at subcutaneous doses 5.

• and 2-times the maximum recommended human dose (MRHD) of 120 mg, respectively The background risk of major birth defects and miscarriage for the indicated populations is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

A reproductive study in pregnant rats given 30 mg/kg of lanreotide by subcutaneous injection every 2 weeks (5 times the human dose, based on body surface area comparisons) resulted in decreased embryo/fetal survival.

A study in pregnant rabbits given subcutaneous injections of 0.45 mg/kg/day (2 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.

The safety and effectiveness of Lanreotide

Injection in pediatric patients have not been established.

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.

Studies and 4, conducted in patients with neuroendocrine tumors, did not include sufficient numbers of patients aged 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.