Lanreotide - Mechanism of Action, Indications, Dosage, and Adverse Drug Reactions

Overview

Acromegaly, a disorder marked by excessive growth hormone release, is treated with Lanreotide. Lanreotide restores insulin-like growth factor-I (IGF-I) levels to normal and lowers growth hormone levels. Although Lanreotide treatment is not a cure, it offers long-term care and is utilized when radiation therapy or surgery is not practical or effective. In one-third of patients, it can return IGF-I levels to normal, and in individuals with acromegaly, it may cause tumor shrinkage. On August 30, 2007, the United States Food and Drug Administration (US FDA) approved Lanreotide for use.

Drug Group

Lanreotide is a long-acting analog of somatostatin or growth hormone inhibitor, functions as a somatostatin receptor ligand, and is used to treat acromegaly and certain neuroendocrine tumors.

What Is Lanreotide Injection Used For?

Lanreotide is indicated for the following conditions:

• Long-term management of patients with acromegaly who have not responded well to surgery and radiation therapy or who are not candidates for these treatments.

• The management of gastroenteropancreatic neuroendocrine tumors or GEP-NETs (tumors that arise from neuroendocrine cells), in adult patients who are unresectable, well-or moderately differentiated, locally progressed, or metastatic to enhance progression-free survival.

Contraindications

Patients with a history of Lanreotide hypersensitivity (an exaggerated immune response) are not advised to get Lanreotide injections due to the possibility of allergic reactions, such as angioedema (swelling under the skin) and anaphylaxis (severe allergic reactions).

Dosage Forms and Available Strengths

Single-dose, prefilled syringes containing semi-solid, white to pale yellow formulations containing Lanreotide acetate in dosages of 60 mg (milligrams) per 0.2 mL (milliliter), 90 mg per 0.3 mL, and 120 mg per 0.5 mL are available.

For Patients

What Is Acromegaly?

A hormonal condition known as acromegaly is brought on by the pituitary gland's overproduction of growth hormones during adulthood. Acromegaly causes a limited increase in bone growth and primarily affects the hands, feet, and face. Typical symptoms include enlarged hands and feet, altered facial features, thicker skin, profuse sweating, and joint pain. Prompt diagnosis of acromegaly is essential for appropriate management and minimizing consequences.

How Does Lanreotide Work?

Lanreotide manages acromegaly symptoms by lowering growth hormone secretion and cell proliferation, normalizing growth hormone levels, and binding to somatostatin receptors, lowering the risk of consequences like diabetes (high blood sugar) and heart disease.

What Are the Clinical Uses of Lanreotide?

Key clinical uses for Lanreotide consist of:

• Management of Acromegaly: Lanreotide helps regulate growth hormone levels by attaching to somatostatin receptors (SSTR2 and SSTR5) on pituitary tumor cells. As a result, symptoms, including larger hands, feet, and facial characteristics, are lessened, and growth hormone secretion decreases.

• Symptom Relief: Lanreotide reduces the symptoms of acromegaly, such as joint pain, fatigue, and sweating, by bringing growth hormone levels back to normal.

• Tumor Stabilization: Lanreotide has the potential to reduce tumor growth and stop pituitary adenomas (a non-cancerous growth on the pituitary) from getting bigger.

• Long-Acting Formulation: The long-acting form of Lanreotide is given as a deep subcutaneous injection every 28 days. Patients tolerate it well, and it offers prolonged growth hormone suppression.

How Is Lanreotide Administered?

• A doctor or nurse administers lanreotide injections subcutaneously, or beneath the skin, into the upper outer region of the buttock. Lanreotide is a long-acting solution (liquid). Typically, Lanreotide long-acting injections are given once every four weeks.

• Depending on the laboratory findings, the doctor will likely change the amount of medication people take or the intervals between doses.

What Are the Side Effects of Lanreotide?

The blood sugar levels may fluctuate while using Lanreotide. People need to understand the signs of high and low blood sugar and what to do if they experience them. Injections of Lanreotide may have adverse effects.

If any of these symptoms of Lanreotide are severe or persistent, let the physician know:

• Diarrhea or loose stools.

• Constipation.

• Gas issue.

• Vomiting.

• Drop in weight.

• Headache.

• Depression.

• Itching, pain, redness, or lump at the injection site.

Certain adverse effects of Lanreotide may be dangerous. Call the doctor right away if people taking Lanreotide have any of these symptoms, or seek emergency care:

• Back, shoulder, upper right stomach, or middle stomach ache.

• Soreness in the muscles

• Yellowing of the eyes and skin.

• Chills and fever.

• Nausea.

• Facial, throat, tongue, lip, or eye swelling.

• Throat tightness.

• Breathing difficulty and difficulty in swallowing.

• Wheezing (a high-pitched whistling sound while breathing).

• Hoarseness.

• Rash.

• Itching.

• Hives (skin rash).

• Dyspnea (shortness of breath).

• Slowed or erratic (irregular) heartbeat.

It is advised that people contact the doctor if they have any unusual side effects while using Lanreotide.

What Are the Things to Inform the Doctor Before Taking Lanreotide?

Inform the doctor of any existing medical problems before receiving Lanreotide, including if people possess

• Gallbladder issues.

• Diabetes.

• Cardiac issues.

• Thyroid issues.

• Issues with the kidneys.

• Liver issues.

Dietary Consideration

Unless advised differently by their physician, people taking Lanreotide can continue eating normally.

Missed Dose

Follow the doctor's instructions and contact them immediately if people need to remember to take the Lanreotide dosage. The doctor can assist in rescheduling the dose if people cannot schedule a visit. Doses should always be included, mainly when using long-acting injectables like Lanreotide.

Overdose

Call the poison control helpline if people overdose. Contact emergency services if the victim passes out, experiences seizures (uncontrolled electrical activity between the brain cells), has trouble breathing, or cannot be awakened.

Storage and Handling

Prefilled Lanreotide syringes should always be kept in the original container in the refrigerator and protected from light if people keep them at home until the doctor or nurse decides to inject them.

Disposal

Lanreotide that is outdated or unnecessary should be thrown away. For guidance on how to properly dispose of Lanreotide, consult a doctor.

For Doctors

Description

The synthetic octapeptide analog of somatostatin, Lanreotide acetate, is the active ingredient of Lanreotide injection, a long-acting deep subcutaneous injection formulation. Lanreotide comes in single-dose prefilled sterile syringes that are ready to use and contain a supersaturated bulk solution of 24.6 percent w/w (weight in weight) Lanreotide base.

[cyclo S-S]-3-(2-naphthyl)-D-alanyl-L-cysteinyl-L-tyrosyl-D-tryptophyl-L-lysyl-L-valyl-L-cysteinyl-L-threoninamide, acetate salt, is the chemical name for Lanreotide acetate. 1096.34 g/mol (gram mole) is its molecular weight (base).

What Are the Pharmacological Aspects of Lanreotide?

Pharmacodynamics

By suppressing cAMP (cyclic adenosine monophosphate) or activating ion currents like K+ (potassium) and Ca2+ (calcium), Lanreotide has antisecretory actions. This causes the membrane to become hyperpolarized and inhibits Ca2+-mediated depolarization. Moreover, Lanreotide significantly reduces cell proliferation by both direct and indirect mechanisms.

Mechanism of Action

The primary effects of Lanreotide, a somatostatin analog (SSA), are inhibitory and mediated through somatostatin receptors (SSTRs) 2 and 5. Lanreotide's mechanism of action includes inhibition of brain growth hormone release. Tumor SSTR activation reduces the production of chemicals that stimulate tumor growth and angiogenesis (blood vessel formation), as well as downstream cell cycle arrest and apoptosis (programmed cell death). This results in Lanreotide's anti-proliferative actions.

Pharmacokinetics

1. Absorption: Lanreotide's absorption at the injection site is divided into two phases due to the creation of a drug depot.

• The first rapid subcutaneous release occurs in the initial few days of treatment and is used to absorb the medication that has not precipitated quickly.

• Drugs are released from the depot gradually by passive diffusion. Dosage, gender, and body weight do not affect absorption.

2. Distribution: The estimated volume of distribution for Lanreotide injection is 15.1 L (3.98 gallons).

3. Excretion: The excretion of Lanreotide is biliary, with less than five percent eliminated in urine and 0.5 percent unchanged in feces. Its estimated clearance is 23.1 L/h (liters per hour), and its half-life is 22 days.

Toxicity

In 67 to 84 percent of patients, gastrointestinal (GI) problems are Lanreotide's most common side effects. These side effects are often mild to moderate, and diarrhea and stomach pain are common companions. Abdominal distension, nausea, and vomiting are other GI symptoms. 43 percent of patients experience injection site adverse effects; these problems are particularly prevalent in patients who self-inject. Some claim to have developed impaired glucose tolerance, diabetes mellitus, or fasting glucose. Due to suppression of GI and gallbladder motility, up to 30 percent of individuals may develop gallstones and sludge within the gallbladder after a year. Other side effects include alopecia, bradycardia, nasopharyngitis, and decreased left ventricular end-diastolic and end-systolic volumes.

What Are the Drug Interactions of Lanreotide?

• Cyclosporine: An injection of Lanreotide may reduce Cyclosporine's absorption. Cyclosporine dosage adjustments can be required.

• Bromocriptine: An injection of Lanreotide may increase Bromocriptine's absorption.

• Beta-Blockers: An injection of Lanreotide has the potential to lower heart rate (bradycardia). Modifying the dosage of the coadministered medication might be required.

Clinical Studies

• The effectiveness of Lanreotide 60, 90, or 120 mg in treating patients with active acromegaly was evaluated in this study. After a 12-week washout, patients were allocated to receive either a single injection of Lanreotide or a placebo. After four weeks, the patients underwent a fixed-dose phase, receiving four Lanreotide injections. This was followed by an eight-injection dose-titration phase for 13 injections over 52 weeks. During the dosage-titration phase, the dose was changed twice. One hundred-eight individuals were included in the first phase, which was placebo-controlled. During the double-blind phase, mean GH decreased by over 50 percent in 63 of 83 Lanreotide-treated patients and by more than 50 percent in 72 percent of all 107 Lanreotide-treated patients from baseline to Week 4. The efficacy attained in the first 16 weeks was retained throughout the study.

• Patients with elevated IGF-1 values in acromegalic patients were taken for a 48-week trial. Dopaminergic agonists or somatostatin analogs were used as a part of the treatment. Injections of 90 mg of Lanreotide were given to the patients every four weeks. After 48 weeks, 43 percent of patients exhibited normal IGF-1 readings. There was a correlation between the decline in mean GH concentrations and the decline in IGF-1 concentrations. Following the fixed-dose phase, the percentage of patients with mean GH concentrations less than 2.5 ng/mL (nanograms per milliliter) increased dramatically from 35 percent to 77 percent after the fixed-dose phase and ultimately to 85 percent at the end of the trial.

Warnings and Precautions

• Cholelithiasis and Complications of Cholelithiasis: Lanreotide may decrease gallbladder motility, which could result in gallstone development. To prevent complications, including pancreatitis, cholangitis, cholelithiasis, and cholecystitis, patients should be monitored periodically. If complications are suspected, treat appropriately and stop using Lanreotide injection.

• Hyperglycemia and Hypoglycemia: Patients may develop hypoglycemia or hyperglycemia due to Lanreotide's inhibition of insulin and glucagon release, similar to other somatostatin analogs. In patients who are at risk, use with caution since cardiovascular problems may arise. Throughout therapy, it is advised to monitor blood glucose levels and modify antidiabetic medication as necessary.

• Thyroid Function Abnormalities: Thyroid function tests are advised when clinically necessary, as Lanreotide medication in acromegalic individuals may result in mild reductions in thyroid function. However, clinical hypothyroidism is uncommon.

• Cardiovascular Abnormalities: The most frequent cardiac events in patients with acromegaly were sinus bradycardia, bradycardia, and hypertension, according to three pooled Lanreotide cardiac studies. The incidence of heart rates below 60 beats per minute (bpm) was 23 percent in 81 Lanreotide-treated patients with baseline heart rates of 60 bpm or above, compared to 16 percent in patients receiving a placebo. In each therapy group, one percent of reported instances of bradycardia and heart rates under 50 bpm were reported as adverse events. Lanreotide may cause a drop in heart rate in individuals without underlying cardiac illness, although it need not result in bradycardia. Patients with bradycardia should be cautious while starting treatment with Lanreotide injection.

Use in Specific Populations

• Pregnancy: As there is insufficient information on the effects of Lanereptide on expectant mothers, it is best to use the medication only if the advantages to the fetus outweigh the risks involved.

• Breastfeeding: It is unknown if Lanreotide is present in human milk, although it was found in rat milk. As breastfeeding may have negative consequences, it is not recommended during therapy or for six months following the final dosage.

• Pediatric Use: The safety and effectiveness of Lanreotide injection in pediatric patients have not been confirmed.

• Geriatric Use: Studies indicate that there are no age-specific difficulties that limit the use of Lanreotide in older individuals; however, age-associated problems relating to the liver, kidneys, or heart may require dose modifications and caution.

• Renal and Hepatic Impairment: The study recommends that patients with moderate to severe renal and hepatic impairment begin with a 60 mg Lanreotide injection and proceed cautiously with longer dosing intervals of 120 mg every six or eight weeks.