Somatuline Autogel 60mg: Each pre-filled syringe contains a supersaturated solution of lanreotide acetate corresponding to 0.246 mg of lanreotide base/mg of solution, which ensures an actual injection dose of 60 mg.
Somatuline Autogel 90mg: Each pre-filled syringe contains a supersaturated solution of lanreotide acetate corresponding to 0.246 mg of lanreotide base/mg of solution, which ensures an actual injection dose of 90 mg.
Somatuline Autogel 120mg: Each pre-filled syringe contains a supersaturated solution of lanreotide acetate corresponding to 0.246 mg of lanreotide base/mg of solution, which ensures an actual injection dose of 120 mg.
Excipients/Inactive Ingredients: Water for injections, acetic acid (for pH adjustment).
Pharmacotherapeutic Group: ANTIGROWTH HORMONE. ATC Code: H01C B03.
Pharmacology: Pharmacodynamics: Lanreotide is an octapeptide analogue of natural somatostatin. Like somatostatin, lanreotide is an inhibitor of various endocrine, neuroendocrine, exocrine and paracrine functions. It shows high binding affinity for human somatostatin receptors (SSTR) 2, 3 and 5, and reduced affinity for human SSTR 1 and 4. Activity on SSTR 2 and 5 is the primary mechanism considered to be responsible for GH inhibition.
Lanreotide, exhibits a general exocrine anti-secretory action. It inhibits the basal secretion of motilin, gastric inhibitory peptide and pancreatic polypeptide, but has no significant effect on fasting secretin or gastrin secretion.
Lanreotide inhibits meal-induced increases in superior mesenteric artery blood flow and portal venous blood flow.
Lanreotide reduces prostaglandin E1-stimulated jejunal hydroelectrlytic secretion.
Lanreotide reduces prolactin levels in patients treated long term.
Lanreotide is far more potent than natural somatostatin and exerts its activity for far longer.
Pharmacokinetics: Pharmacokinetic parameters of lanreotide after intravenous administration in healthy volunteers are consistent with a short duration of action : steady-state volume of distribution of 13L, clearance of 20 L/h, terminal half-life of 2.5 hours and mean residence time of 0.68 hours. By contrast, the kinetic parameters of lanreotide administered in the form of Somatuline Autogel by the intramuscular or sub-cutaneous route explain its 28-day duration of action. In healthy volunteers, doses of 60 mg, 90 mg and 120 mg showed a terminal elimination half-life and mean residence time of approximately 4 weeks.
The route of administration (sub-cutaneous or intramuscular) has no significant influence on lanreotide pharmacokinetic profiles. Plasma concentrations plotted against the dose administered are almost log-linear with slight individual variations. Absolute bioavailability is approximately 60%.
After a single subcutaneous injection of Somatuline Augogel 60 mg in healthy volunteers, a maximum serum concentration (Cmax) of 5.8 ± 4 ng/ml was reached after 6 hours, followed by a slow decrease (mean residence time: 30 ± 6 days, apparent half-life: 33 ± 14 days). The absolute bioavailability was 63 ± 10%.
After a single intramuscular injection of Somatuline Autogel 60 mg in healthy volunteers, a maximum serum concentration (Cmax) of 6.8 ± 3 ng/ml was reached after 15 hours, followed by a slow decrease (mean residence time: 23 ± 11 days, apparent half-life: 23 ± 9 days). The absolute bioavailability was 79 ± 10%.
After a single intramuscular injection of Somatuline Autogel 90 mg in healthy volunteers, a maximum serum concentration (Cmax) of 9.8 ± 5 ng/ml was reached after 10 hours, followed by a slow decrease (mean residence time: 26 ± 4 days, apparent half-life: 31 ± 16 days). The absolute bioavailability was 58 ± 10%.
After a single intramuscular injection of Somatuline Autogel 120 mg in healthy volunteers, a maximum serum concentration (Cmax) of 12.8 ± 7 ng/ml was reached after 16 hours, followed by a slow decrease (mean residence time: 29 ± 3 days, apparent half-life: 28 ± 6 days). The absolute bioavailability was 55 ± 10%.
Trough lanreotide serum levels obtained after three deep subcutaneous injections of Somatuline Autogel 60, 90 or 120 mg given every 28 days are similar to the steady-state trough lanreotide serum levels obtained in acromegalic patients previously treated with intramuscular administrations of SOMATULINE P.R. 30 mg, powder and solvent for prolonged release suspension for injection (IM).
The supersaturated solution of lanreotide releases active substance over 28 days with an initial, dose-adjusted Cmax less than that obtained after the administration of SOMATULINE P.R. 30 mg, powder and solvent for prolonged release suspension for injection (I.M.).
Toxicology: Preclinical safety data: In vitro and animal toxicology studies have not shown any specific toxic potential for lanreotide. The observed effects are related to the pharmacological properties of lanreotide on the endocrine system.
Treatment of acromegaly when secretions of Growth Hormone (GH) and Insulin-like Growth Hormone (GH) and Insulin-like Growth Factor-1 (IGF-1) remain abnormal after surgery and/or radiotherapy.
Treatment of the clinical symptoms associated with acromegaly.
Treatment of the clinical symptoms of neuroendocrine (particularly carcinoid) tumours.
Initiation of treatment: Acromegaly: The recommended starting dose is 60 to 120 mg administered every 28 days.
For example: in patients previously treated with SOMATULINE P.R. 30 mg powder and solvent for prolonged-release suspension for injection (I.M.) every 14 days, the initial dose of Somatuline Autogel should be 60 mg every 28 days;
in patients previously treated with SOMATULINE P.R. 30 mg powder and solvent for prolonged-release suspension for injection (I.M.) every 10 days, the initial dose of Somatuline Autogel should be 90 mg every 28 days;
in patients previously treated with SOMATULINE P.R. 30 mg powder and solvent for prolonged-release suspension for injection (I.M.) every 7 days, the initial dose of Somatuline Autogel should be 120 mg every 28 days.
Neuroendocrine tumours: The recommended starting dose is 60 to 120 mg administered every 28 days. The dose should be adjusted according to the degree of symptomatic relief obtained.
Adaptation of treatment: The treatment should be adjusted for each patient in a specialised unit.
The dose should be individualised according to the response which is evaluated by monitoring plasma GH and IGF-1 levels and by assessing changes in symptoms.
Acromegaly: It is recommended: to reduce the dose when the concentrations are normalised (GH < 1 ng/ml and normalised IGF-1 and/or disappearance of clinical symptoms),
to maintain the dose when the concentrations of GH are between 2.5 ng/ml and 1 ng/ml,
to increase the dose when the concentrations of GH are higher than 2.5 ng/ml.
Patients well controlled on a somatostatin analogue can be treated with Somatuline Autogel 120 mg every 42 or 56 days.
Neuroendocrine tumours: In case of an insufficient response judged by clinical symptom (flushes and soft stools), the dose may be increased to 120 mg every 28 days (4 weeks).
In case of a sufficient response judged by clinical symptom (flushed and soft stools), the dose may be decreased to 60 mg every 28 days (4 weeks).
Method of administration: The solution should be injected via the deep sub-cutaneous route in the superior external quadrant of the buttock.
The injection is made by healthcare professional. However, for patients receiving stable dose of SOMATULINE the product may be administered either by the patient or by a person around him after appropriate training by a healthcare professional. In case of self-injection the injection should be given in the upper outer thigh.
The decision to allow administration by the patient or a trained person should be made by healthcare professional.
Regardless of the site of injection, the skin should not be folded and the needle should be inserted rapidly to its full length, perpendicularly to the skin.
The injection site should alternate between the right and left side.
In clinical trials, lanreotide has been administered in doses up to 15 mg per day without serious adverse events related to the treatment.
If overdosage occurs, symptomatic management is indicated.
Complicated, untreated lithiasis of the bile ducts, pregnancy and lactation, hypersensitivity to lanreotide or to products of the same class.
Pharmacological studies in an animals and humans show that lanreotide, like somatostatin and its analogues, may produce a transient inhibition of the secretion of insulin and glucagon. Thus, blood glucose levels should be monitored in diabetic patients in order to determine whether anti-diabetic treatment needs to be adjusted.
Lanreotide reduces gall bladder motility. Thus, the gall bladder echography may be advisable systemically in all patients who have not undergone cholecystectomy, and this both at the start and in the course of the treatment. The incidence of cholelithiasis and sludge bladder increases with the dose and the duration of treatment. If gallstones do occur, they are usually asymptomatic. Subjects with severe renal impairment have shown an approximate 2-fold decrease in total clearance of lanreotide with a consequent increase in half-life and AUC (area under the curve).
Subjects with hepatic impairment have shown an increase in volume of distribution and mean residence time, but without any modification in total clearance or AUC.
Elderly subjects have shown an increase in half-life and mean residence time compared with healthy young subjects. Due to the wide therapeutic window shown by lanreotide, it is not necessary to adapt the dose in these circumstances.
Effects on ability to drive and use machines: Not applicable.
Pregnancy: Studies in animals have not shown any teratogenic effects. Thus, no malformations are expected in humans since substances responsible for such malformations have been shown to produce teratogenic effects in animals during well-conducted studies in two different animal species.
In clinical practice, no relevant information is currently available to evaluate whether this medication causes malformations or foetotoxicity. However, in view of its pharmacological activity (growth hormone antagonism), this medication is contra-indicated in pregnant women.
In addition, effects on fertility have been noted in adult male animals receiving the treatment.
Lactation: Breast-feeding is contraindicated in women receiving this medication.
This adverse effects observed in clinical trials with Somatuline Autogel are consistent on a quantity and quality point of view with those seen with other prolonged release formulations of lanreotide, and are predominantly gastrointestinal.
In clinical trials of Somatuline Autogel in acromegalic patients, 80 % of patients experienced at least 1 adverse event. More than 50% of these adverse events were classified as gastro-intestinal system disorders. The most commonly reported adverse reactions are diarrhoea, abdominal pain and nausea. These reactions are usually mild and transient.
Very common adverse effects
(more than 10% of patients): diarrhoea, abdominal pain, nausea, cholelithiasis or gall bladder sludge.
Common adverse effects
(between 5 and 10% of patients): constipation, flatulence.
Less common adverse effects
(between 1 and 5% of patients): asthenia, fatigue, increased bilirubin.
Uncommon adverse effects
(less than 1% of patients): injection site pain, skin nodule, hot flushes, leg pain, malaise, headache, tenesmus, vomiting, abnormal glucose tolerance, hyperglycemia, decreased libido, somnolence, pruritus, increased sweating.
Some patients showed a reaction at the injection site 30 minutes after dosing, e.g. pain (up to 8% of cases), redness (up to 5 %), itching (up to 5 %) and induration (up to 19 %). After 3 injections, these clinical signs affected only 6 %, 2 %, 3 % and 9 % of patients respectively. In all cases, these signs were described as moderate.
Combinations requiring precautions for use: Cyclosporin (oral route): the concomitant injection of lanreotide with cyclosporin may decrease blood levels of cyclosporin. Blood concentration of cyclosporin should therefore be monitored during treatment with Somatuline Autogel and after the treatment has been withdrawn.
Insulin: risk of hypoglycaemia: decrease in the needs of insulin following the decrease in endogen glucagon secretion. The patient must be informed of the risk of hypoglycemia, the glycemic and urinary self-monitoring must be reinforced and the posology of insulin during treatment by lanreotide should be adapted.
Interactions with highly plasma bound drugs are unlikely in view of the moderate binding of lanreotide to serum proteins (78 % mean serum binding).
Instruction for use and handling: The Somatuline Autogel prolonged-release solution for injection in a pre-filled syringe is a ready-for use supersaturated lanreotide solution that forms a whitish, translucent autogel.
For immediate and single use following first opening.
It is important that the injection of the product is performed exactly according to the instruction in the package leaflet.
Do not use if the laminated pouch is damaged or opened.
Any unused product or waste material should be disposed of in accordance with local requirements.
The following instruction explain how to inject Lanreotide Autogel.
PLEASE READ ALL THE INSTRUCTIONS CAREFULLY BEFORE STARTING THE INJECTION.
Lanreotide Autogel is supplied in a ready to use pre-filled syringe fitted with an automatic safety system that automatically locks in place following administration of the product, to help prevent needle stick injury after use.
1. Remove Lanreotide Autogel from the refrigerator 30 minutes prior to administration. Keep pouch sealed until just prior to injection.
2. Before opening the pouch, check that it is intact and that the medication has not expired. The expiration date is printed on the outer carton and the pouch. DO NOT USE IF THE MEDICATION HAS EXPIRED OR IF THE LAMINATED POUCH IS DAMAGED IN ANY WAY.
3. Tear-open the pouch and take out the pre-filled syringe.
4. Select an injection site: 4a: the superior external quadrant of the buttock (for injection by healthcare professional (HCP) or someone else like a trained family member or friend),
4b: the upper outer part of your thigh (if you will be injecting yourself).
Alternate the injection site between the right and left side each time you receive an injection of Lanreotide Autogel.
5. Twist and pull off the plunger protector and discard it.
6. Remove the needle cap and discard it.
7. Hold the skin around the injection site flat using your thumb and index finger. Without folding or pressing on the skin at the injection site, rapidly insert the needle to its full length (deep subcutaneous injection), perpendicular (90°) to the skin.
8. Inject the drug slowly. Typically 20 seconds are needed. Inject the full dose until the plunger cannot be depressed any further. At this point, you will hear a "click".
Note: maintain pressure on the plunger with your thumb to avoid activation of the automatic safety system.
9. Without releasing the pressure on the plunger, withdraw the needle from the injection site.
10. Then release pressure on the plunger. The needle will automatically retract into the needle guard where it will be locked permanently.
11. 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.
12. Dispose of the used syringe as instructed by your doctor or healthcare provider. DO NOT dispose of the device in your general household rubbish.
Incompatibilities: Not applicable.
Store at + 2°C to + 8°C (refrigerator).
Shelf-Life: 2 years.
After opening the protective laminated pouch, the product should be administered immediately.
H01CB03 - lanreotide ; Belongs to the class of antigrowth hormone. Used in hypothalamic hormone preparations.
PR soln for inj (prolonged-release, white to pale yellow semi-solid formulation in pre-filled syringe) 60 mg x 0.5 mL x 1's. 90 mg x 0.5 mL x 1's. 120 mg x 0.5 mL x 1's.