Somatuline^® Autogel (Gel) Instructions for Use

ATC Code

H01CB03 (Lanreotide)

Active Substance

Lanreotide

Clinical-Pharmacological Group

Somatostatin analogue

Pharmacotherapeutic Group

Somatostatin (synthetic analogue)

Pharmacological Action

Synthetic analogue of natural somatostatin, a synthetic peptide.

Similar to natural somatostatin, Lanreotide suppresses a number of endocrine, exocrine, and paracrine mechanisms. A pronounced tropism of lanreotide for human somatostatin receptors (SSR)-2, 3, and 5, and low tropism for SSR-1 and 4 has been identified. It is believed that the activation of SSR-2 and 5 is the main mechanism underlying the suppression of growth hormone (GH) secretion.

Lanreotide, like somatostatin, has a general exocrine antisecretory effect. It suppresses the basal secretion of gastric inhibitory peptides and pancreatic polypeptides, but does not affect the secretion of digestive enzymes or gastric secretion. Lanreotide significantly suppresses the food-induced increase in blood flow in the upper mesenteric artery and portal vein. Lanreotide significantly reduces prostaglandin E1-stimulated secretion of water, sodium, potassium, and chlorides in the jejunum.

Lanreotide reduces prolactin levels in patients with acromegaly receiving long-term treatment.

Pharmacokinetics

Unlike the indicators after IV administration, the pharmacokinetic profiles of lanreotide in the prolonged-release dosage form administered IM or deep SC showed the duration of the drug’s action for 28 days.

The method of drug administration (SC or IM) does not have any effect on the pharmacokinetic parameters of lanreotide. The plasma concentration level showed dose-dependent linearity with minor deviations associated with individual characteristics of the study participants.

Absorption

After a single deep SC administration of Somatuline^® Autogel^® 120 mg to healthy volunteers, the C_max in serum was 6.79 ng/ml and was reached after 7 hours, followed by a slow decrease (mean T_1/2 was 30.1 days). After 4 weeks, the mean serum drug concentration was 1.69 ng/ml. The absolute bioavailability was 78.4%.

After a single deep SC administration of Somatuline^® Autogel^® 120 mg to patients with acromegaly, the C_max value was 3.1 ng/ml and was reached after 23.52 hours, followed by a slow decrease. After 4 weeks, the mean serum drug concentration was 1.4 ng/ml.

On average, after 4 injections administered every 4 weeks, the C_ss of lanreotide in plasma was achieved. The mean C_ss^max value was 7.7 ng/ml at a dose of 120 mg. The mean C_min value was 3.8 ng/ml.

Distribution

Pharmacokinetic parameters of lanreotide after IV administration to healthy volunteers revealed limited extravascular distribution with a V_d at steady state of 13 L.

Elimination

After IV administration to healthy volunteers, the total clearance was 20 L/h, T_1/2 was 2.5 hours, and the mean plasma residence time was 0.68 hours.

After injections of Somatuline^® Autogel^® 120 mg to healthy volunteers, the T_1/2 was approximately 28 days.

Indications

Acromegaly (to reduce the level of GH and insulin-like growth factor-1 /IGF-1/ and, if possible, normalize them)

• Long-term therapy of patients in whom the level of GH and/or insulin-like growth factor-1 (IGF-1) remains elevated after surgical treatment and/or radiation therapy;
• Long-term therapy of patients who require drug therapy (the goal of acromegaly therapy is to reduce GH and IGF-1 and, if possible, normalize these indicators).

Therapy of symptoms of carcinoid tumors.

ICD codes

Dosage Regimen

Gel

Acromegaly

The recommended initial dose is 120 mg every 28 days.

Patients who have achieved effective disease control with somatostatin analogue therapy may be prescribed Somatuline^® Autogel^® at a dose of 120 mg with an increased interval – every 42-56 days. In these patients, clinical symptoms and levels of GH and IGF-1 should be monitored regularly and in the long term.

All patients should have regular monitoring of clinical symptoms, GH and IGF-1 levels.

Carcinoid tumors

The recommended initial dose is 120 mg every 28 days. Subsequently, the dose should be adjusted depending on the achieved reduction in symptoms.

Patients who have achieved effective disease control with somatostatin analogue therapy may be prescribed Somatuline^® Autogel^® at a dose of 120 mg with an increased interval – every 42-56 days.

Drug Administration Rules

The prolonged-release gel for SC administration is supplied in a pre-filled syringe equipped with a safety device that automatically covers the needle immediately after injection, thereby helping to prevent accidental needle sticks after use.

The drug should be administered deep SC immediately after opening the package.

1 syringe with the drug is intended for single use only.

The drug is administered by medical personnel into the upper outer quadrant of the buttock.

If the patient is receiving a stable dose of Somatuline^® Autogel^®, injections can be administered at home by the patients themselves or their relatives after appropriate prior training by a doctor. When self-administering the injection by the patient, the drug should be injected into the upper thigh.

When administering the drug, the following instructions should be observed.

1. Remove Somatuline^® Autogel^® from the refrigerator 30 minutes before use.
2. Ensure a clean area for preparatory actions and wash your hands.
3. Before opening, check the integrity of the bag containing the syringe with the drug. Also, it is necessary to ensure that the drug has not expired. The expiration date is present on the bag label. Do not use the drug if the bag integrity is compromised or after the expiration date.
4. Open the bag and remove the syringe with the safety device from it.
5. Choose the site for the intended injection. Disinfect the intended injection site (upper thigh or upper outer quadrant of the buttock), avoiding rubbing the skin. The injection is given alternately each time, either in the left or right buttock or thigh.
6. Turn and pull the plunger rod safety device, then remove it.
7. Remove the needle cap.
8. Insert the needle into the upper thigh or upper outer quadrant of the buttock without pinching the skinfold, but holding the skin with the thumb and forefinger.

The needle should be inserted quickly, to its full length, perpendicular to the skin surface (deep subcutaneous injection).

1. Slowly inject the entire drug, applying constant, even pressure on the plunger, while keeping the needle stationary (usually about 20 seconds are required for complete drug administration). At the moment when the plunger completely passes through the entire syringe body and rests against the opposite end, a click is heard.

Note: continue to hold the plunger pressed to avoid activation of the safety device.

1. While holding the plunger, remove the needle from the injection site.
2. After that, release the plunger, the needle will automatically retract into the safety device tube and lock in it.
3. Gently apply a dry cotton pad or sterile wipe to the injection site to prevent bleeding. Do not rub or massage the drug injection site after injection.
4. Dispose of the used syringe according to instructions.

Adverse Reactions

Adverse reactions identified during clinical studies with the use of Somatuline^® Autogel^® are similar to those observed with the use of other prolonged-release dosage forms of lanreotide and are mainly disorders of the digestive system.

In clinical studies of Somatuline^® Autogel^® in the treatment of patients with acromegaly, at least 1 adverse event was observed in 80% of patients. More than 50% of these adverse events were attributed to disorders of the digestive system. These side effects are usually mild and transient.

Digestive system very often (> 10%) – diarrhea, abdominal pain, nausea, cholelithiasis or gallbladder sludge syndrome; often (> 5%, but < 10%) – constipation, flatulence, anorexia; infrequently (>1%, but < 5%) – increased bilirubin concentration; very rarely (< 1%) – tenesmus, vomiting, acute pancreatitis, steatorrhea.

Cardiovascular system often (> 5%, but < 10%) – sinus bradycardia.

Metabolism often (> 5%, but < 10%) – hypoglycemia; very rarely (< 1%) – worsening of diabetes mellitus, impaired glucose tolerance, hyperglycemia.

Dermatological reactions very rarely (< 1%) – hair loss, itching, increased sweating, skin reactions (non-specific).

Local reactions very rarely (< 1%) – pain at the injection site, skin swelling. 30 minutes after deep SC injection of Somatuline^® Autogel^®, pain, redness, itching, and induration may be observed in the injection area in 8%, 5%, 5%, and 19% of patients, respectively. After the 3rd injection, the frequency of these symptoms decreases and is observed in 6%, 2%, 3%, and 9% of patients. In all cases, the symptoms were mild.

Other often (> 5%, but < 10%) – dizziness, allergic skin reactions; infrequently (>1%, but < 5%) – weakness, fatigue; very rarely (< 1%) – feeling of heat, leg pain, malaise, headache, decreased libido, drowsiness.

Contraindications

• Complicated, untreated choledocholithiasis;
• Pregnancy;
• Lactation;
• Childhood (due to insufficient clinical data);
• Hypersensitivity to lanreotide or related peptides.

Use in Pregnancy and Lactation

Adequate and strictly controlled clinical studies on the safety of the drug during pregnancy have not been conducted.

In experimental studies on the effect on reproduction in rats and rabbits with the drug in doses 33 times higher than the doses used in humans, no risk to the fetus was identified. Since studies on reproduction in animals do not always predict the effect on reproduction in humans, this drug is contraindicated during pregnancy.

The use of the drug during lactation (breastfeeding) is contraindicated.

Pediatric Use

Contraindicated in childhood.

Special Precautions

Pharmacological studies in animals and humans have shown that Lanreotide, like somatostatin and its analogues, can cause transient inhibition of insulin and glucagon secretion. Therefore, in patients with diabetes mellitus receiving treatment with Somatuline^® Autogel^®, minor short-term changes in blood glucose levels may be observed. To determine the need for adjustment of antidiabetic therapy, blood glucose levels should be monitored.

During the treatment of patients with acromegaly, a slight decrease in thyroid function is possible, but clinical hypothyroidism is rare (<1%). In this regard, monitoring of thyroid function is indicated.

Lanreotide can cause the formation of gallstones, so an ultrasound of the gallbladder is indicated both at the beginning of treatment and during its course. Cholelithiasis is usually asymptomatic. If symptoms of gallstone disease appear, treatment is required.

In patients with severe renal impairment, an approximately 2-fold decrease in the total plasma clearance of lanreotide is observed with a consequent increase in T_1/2 and AUC. In case of liver dysfunction, an increase in the volume of distribution and mean plasma residence time of lanreotide is observed, but there are no changes in total clearance or AUC. In elderly patients, an increase in the half-life and mean plasma residence time of lanreotide was found compared to young healthy individuals. Due to the large therapeutic range of lanreotide, there is no need to change its dose in these cases.

Effect on ability to drive vehicles and mechanisms

It is unlikely that the ability to drive vehicles and work with mechanisms is impaired during treatment with Somatuline^® Autogel^®.

Overdose

Symptoms in clinical studies, Lanreotide was used in doses exceeding 15 mg/day, and no serious adverse events were identified during treatment. The description of lanreotide overdose in the prolonged-release dosage form in humans is limited to one case where, it was reported, a patient received Lanreotide IM at a dose of 30 mg in the prolonged-release form daily for 2 months (instead of 1 injection every 7 or 14 days). One week after the end of therapy, a 52-year-old man with acromegaly, diabetes mellitus, and arterial hypertension developed a fatal myocardial infarction.

Treatment in case of overdose, symptomatic therapy is indicated.

Drug Interactions

With simultaneous use of lanreotide and cyclosporine, a decrease in the plasma concentration of cyclosporine is possible, so its blood concentration should be monitored.

Interaction with drugs characterized by high binding to plasma proteins is unlikely due to the weak binding of lanreotide to plasma proteins (on average 78%).

Storage Conditions

The drug should be stored out of the reach of children at a temperature from 2°C (35.6°F) to 8°C (46.4°F) (in the refrigerator); do not freeze.

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.