Leuprorelin Acetate - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Leuprorelin acetate is a nonapeptide synthetic drug that is used as a gonadotropin-releasing hormone receptor (GnRHR) agonist. Leuprorelin acetate acts by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone, which further suppresses gonadal sex steroid production.

It has various clinical applications, like the treatment of prostate cancer, uterine fibroids, endometriosis, central precocious puberty, and in vitro fertilization techniques. Several studies reveal that suppression of serum gonadotropins by GnRH agonists can be used in other important clinical applications, like the treatment of Alzheimer's disease, functional bowel disease, polycystic ovary syndrome, short stature, premenstrual syndrome, and as an alternative for contraception.

Uses of Leuprorelin Acetate:

Leuprolide is approved by the United States Food and Drug Administration for the management of:

• Advanced prostate cancer.

• Endometriosis.

• Uterine leiomyomata or uterine fibroids.

• Central precocious puberty in children.

In advanced prostate cancer, Leuprorelin acetate is used as a symptomatic treatment and helps to improve quality of life and reduce comorbidities. Leuprorelin acetate also reduces testosterone levels, which further minimizes the stimulatory effect on androgen-sensitive prostate cancer cells, leading to apoptosis of the cells.

Off-label uses of this medication include:

• Management of breast cancer.

• Hormone therapy for male-to-female transgender patients.

• Management of paraphilia (intense sexual desire for atypical situations, objects, and fantasies) and hypersexuality.

• Premenopausal ovarian suppression.

Warnings:

Before initiating the treatment with Leuprorelin acetate, pregnancy should be excluded. The safe use of Leuprorelin acetate in pregnancy has not been studied clinically yet. It is recommended to periodically monitor the serum testosterone and prostate-specific antigen (PSA) levels, particularly if the desired clinical or biochemical response to treatment has not been achieved.

Initially, Leuprorelin acetate, like other Luteinizing hormone-releasing hormone (LH-RH) agonists, leads to an increase in serum levels of testosterone. There is a transient worsening of symptoms along with the occurrence of a few signs and symptoms of prostate cancer that might develop during the first few weeks of Leuprorelin acetate treatment.

Few of the patients might experience a temporary increase in bone pain that is managed symptomatically. Isolated cases of ureteral obstruction and spinal cord compression have been documented, which might lead to paralysis with or without fatal complications.

Precautions:

Patients with the following conditions should be closely observed during the first few weeks of therapy:

• Metastatic vertebral lesions.

• Urinary tract obstruction.

For Patients:

What Is Leuprorelin Acetate Used For?

Leuprorelin acetate is used for treating advanced prostate cancer. and centrall precocious puberty. Leuprorelin acetate is used alone or with another medication for treating endometriosis, a condition where the tissue lining the uterus grows in other parts of the body, causing pain, and irregular or heavy menstruation. Leuprolide is also used with other medications to treat anemia caused by uterine fibroids or noncancerous uterine growth.

How Is Leuprorelin Acetate Used?

Leuprorelin acetate is available as a long-acting suspension. The medicine is injected intramuscularly by a nurse or a doctor in a clinic and is administered once a month or every three, four, or six months.

Leuprolide injection is also available as a long-acting suspension that is injected subcutaneously by a doctor or nurse in a clinic and is administered every one, three, four, or six months. The doctor informs the patient about the duration of the treatment.

When a long-acting suspension of Leuprolide is administered as a subcutaneous injection, a small bump might be noticed at the site of the injection, which resolves gradually.

Leuprolide can lead to elevated levels of certain hormones in the first few weeks after injection, and the doctor must carefully monitor any new or worsening symptoms during this time.

What Are the Drug Warnings and Precautions?

Allergies: Inform the doctor in case of allergy to Leuprolide, Histrelin, Goserelin, Nafarelin, Triptorelin, or any of the ingredients in the Leuprolide injection.

Drug History: The patient must inform the doctor about the prescription and nonprescription medications, nutritional supplements, herbal products, or vitamins that the patient is taking. The patient should inform the doctor about the following medications:

• Amiodarone.

• Disopyramide.

• Procainamide.

• Quinidine.

• Sotalol.

• Buproprion.

• Dexamethasone.

• Methylprednisolone.

• Prednisone.

• Citalopram.

• Scitalopram.

• Fluoxetine.

• Fluvoxamine

• Paroxetine.

• Sertraline.

Various medications interact with Leuprolide. Hence, it is advised that the patient must inform the doctor about all the medications that they are taking. The doctor might change the doses of the medications or monitor for side effects. Inform the doctor in case of any unusual vaginal bleeding. The doctor might stop the use of this medicine immediately.

Medical History: The patients must inform the doctor if they have or have ever had the following conditions:

• Osteoporosis.

• Depression.

• Brain tumors.

• Seizures.

• Cancer that has spread to the spine (backbone).

• Diabetes.

• Blood in the urine.

• Urinary obstruction (blockage that causes difficulty urinating).

• A prolonged QT interval (a rare heart problem leading to irregular heartbeat, or sudden death).

• Heart disease.

• Cerebrovascular disease.

• Low levels of calcium, potassium, or magnesium in the blood.

Alcohol:

The patient must inform the doctor about a history of drinking alcohol or using tobacco products for a long period of time.

Pregnant or Breastfeeding Women:

Leuprolide is not advised to be used in women who are pregnant, can become pregnant, or are breastfeeding. The patient must inform the doctor if she is pregnant, is planning to become pregnant, or is breastfeeding. The doctor usually performs a pregnancy test before starting this medication. A non-hormonal birth control method is suggested to patients to avoid conception during the treatment. The patient must inform the doctor immediately if she gets pregnant while taking this medication, as Leuprolide can be harmful to the fetus.

What Special Dietary Instructions Must Be Followed?

The normal diet must be continued unless the doctor says otherwise.

What Should Be Done in Case of a Missed Dose?

If the patient has missed an appointment for receiving an injection of Leuprolide, the healthcare provider right away reschedule the appointment.

What Are the Side Effects of Leuprorelin Acetate?

Leuprorelin acetate might cause the following side effects:

• Hot flashes, sweating, or clamminess.

• Tiredness.

• Breast tenderness, or alterations in breast size in both men and women.

• Spotting or menstruation.

• Vaginal discharge, itching, or dryness in women.

• Decrease in the size of testicles.

• Decrease in sexual ability or desire.

• Swelling of the hands, ankles, feet, or lower legs.

• Pain, bruising, burning, redness, or hardening at the site of injection.

• Pain, tingling, or burning in the hands or feet.

• Change in weight.

• Muscle or joint pain.

• Constipation.

• Runny nose, sore throat, cough, or flu-like symptoms.

• Fever.

• Difficulty with memory.

• Stomach pain.

• Headache.

• Acne.

• Depression.

• Unable to control emotions and frequent mood changes.

• A general feeling of discomfort or uneasiness.

• Nervousness.

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• Itching, rash, or hives.

• Difficulty breathing or swallowing.

• Pain in the arms, back, chest, neck, or jaw.

• Slow or difficult speech.

• Weakness, numbness, or inability to move an arm or leg.

• Dizziness or fainting.

• Blood in the urine.

• Bone pain.

• Frequent, painful, difficult urination.

• Extreme thirst.

• Weakness.

• Dry mouth

• Nausea.

• Sudden headache.

• Vomiting.

• Breath that smells fruity.

• Decreased consciousness.

• Blurred vision.

• Vision changes.

• Confusion.

• Seizures.

• Difficulty moving eyes.

• Drooping eyelids.

Leuprorelin acetate can reduce the density of the bones, which can increase the chance of broken bones. The doctor must inform the patient about the risks of using the medication and what must be done to decrease these risks.

What Should Be Done in Case of an Emergency or Overdose?

In case of an overdose, the poison control cell must be informed. Emergency services must be contacted if the following symptoms appear:

• Collapsing.

• Seizure.

• Trouble breathing.

Other Important Information:

• All the appointments with the doctor and the laboratory must be maintained adequately.

• The doctor might suggest blood tests to evaluate the body's response to Leuprorelin acetate before every injection.

• The blood sugar and glycosylated hemoglobin (HbA1c) of the patient should be monitored regularly.

• It is essential for the patient to keep a written list of all of the prescribed and nonprescribed (over-the-counter) medications that the patient is taking.

• The doctor must carry the list for every visit to the doctor or if admitted to a hospital in case of any emergencies.

For Doctors:

Leuprorelin acetate is a synthetic analog of naturally occurring gonadotropin-releasing hormone (GnRH). The analog has greater potency than the natural hormone.

Indications:

Leuprorelin acetate is indicated in advanced prostatic cancer for palliative treatment.

Leuprorelin Injection:

It is an aqueous, sterile, solution intended for subcutaneous injection. It comes in a 2.8-millimeter multiple-dose vial containing the following ingredients:

• Leuprorelin acetate - 5 milligrams per milliliter.

• Sodium chloride for tonicity adjustment - 6.3 milligrams per milliliter.

• Benzyl alcohol as a preservative - 9 milligrams per milliliter.

• Water for injection.

The pH is adjusted with sodium hydroxide and acetic acid.

Pharmacology:

Various animal and human studies prove that, after an initial stimulation of gonadotropins, chronic administration of Leuprorelin acetate suppresses the development of steroids in the ovaries and testes.

Leuprorelin acetate is a Luteinizing hormone-releasing hormone (LH-RH) agonist, that works as a potent inhibitor of gonadotropin secretion if it is administered continuously and in therapeutic doses.

This effect can be reversed by discontinuing the drug therapy. Leuprorelin acetate administration further leads to the inhibition of the growth of certain hormone-dependent tumors and the atrophy of the reproductive organs.

In humans, subcutaneous administration of single daily doses of Leuprorelin acetate causes an increase in circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) initially. This leads to a transient increase in levels of gonadal steroids:

• Testosterone and dihydrotestosterone in males.

• Estrone and estradiol in premenopausal females.

However, daily continuous administration of Leuprorelin acetate can lead to a decrease in the levels of LH and FSH. These decreased levels are observed within two to four weeks after starting the treatment. Leuprorelin acetate is not active if administered orally.

Pharmacokinetics

Distribution

The in vitro binding to human plasma proteins ranges between 43 to 49 percent. The mean steady-state volume of distribution of Leuprolide after intravenous bolus administration to healthy male volunteers was recorded to be 27 liters. Metabolism In healthy male volunteers, a 1-milligram bolus of Leuprolide given intravenously showed that the mean systemic clearance was 7.6 liters per hour, with a terminal elimination half-life of three hours (approximately) based on a two-compartment model.

In dogs and rats, administration of 14C-labeled Leuprolide was recorded to be metabolized to smaller, inactive peptides, a pentapeptide, tripeptides, and a dipeptide.

These fragments might be catabolized further. The major metabolite (M-I) plasma concentrations evaluated in five prostate cancer patients reached maximum concentrations two to six hours after dosing and were recorded to be approximately six percent of the peak parent drug concentration. After one week of dosing, mean plasma M-I concentrations were 20 percent (approximately) of mean Leuprolide concentrations.

Absorption

Bioavailability through subcutaneous administration is similar to that of intravenous administration.

Excretion

After the administration of Leuprorelin acetate 3.75 milligrams to three patients, less than five percent of the dosage was recovered as a parent and M-I metabolite in the urine.

Special Populations

The pharmacokinetics of this medicine was not studied in hepatically and renally impaired patients.

Drug Interactions

No pharmacokinetic-based drug interaction data is available for Leuprorelin acetate and no studies have been conducted. However, Leuprorelin acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes documented in specific studies. This medication is only about 46 percent bound to plasma proteins, and drug interactions are not expected to occur.

Clinical Studies:

In a controlled study comparing Leuprorelin acetate one milligram/day administered subcutaneously to three milligrams/day of DES (Diethylstilbestrol), the survival rate for the two groups after two years of treatment was comparable. The objective response to treatment was also similar for the two groups.

Contraindication:

• It is contraindicated in patients hypersensitive to GnRH, GnRH agonist analogs, or any of the excipients of Leuprorelin acetate.

• It is contraindicated in women who are pregnant or are planning to become pregnant while receiving the Leuprorelin acetate as it might cause fetal harm when administered to a pregnant woman. Therefore, spontaneous abortion might occur if the drug is given during pregnancy. If this drug is administered during pregnancy or if the patient becomes pregnant while taking the drug, the patient must be informed about the potential harm to the fetus.

Adverse Effects:

The medication might cause hypersensitivity in patients with allergies to benzyl alcohol, an ingredient of the medication, in the form of erythema and induration at the injection site.