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Leuprolide is a synthetic nonapeptide analogue of gonadotropin-releasing hormone. Leuprolide binds to and activates gonadotropin-releasing hormone (GnRH) receptors. Continuous, prolonged administration of leuprolide in males results in pituitary GnRH receptor desensitization and inhibition of pituitary secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), leading to a significant decline in testosterone production; in females, prolonged administration results in a decrease in estradiol production. This agent reduces testosterone production to castration levels and may inhibit androgen receptor-positive tumor progression.
Leuprorelin is a manufactured version of a hormone used to treat prostate cancer, breast cancer, endometriosis, uterine fibroids, and early puberty.It is given by injection into a muscle or under the skin.Leuprolide belongs to the general class of drugs known as hormones or hormone antagonists. It is a synthetic 9 residue peptide analog of gonadotropin releasing.
Mechanism of Action of Leuprorelin
Leuprorelin acts as an agonist at pituitary GnRH receptors. By interrupting the normal pulsatile stimulation of, and thus desensitizing, the GnRH receptors, it indirectly downregulates the secretion of gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), leading to hypogonadism and thus a dramatic reduction in estradiol and testosterone levels regardless of sex.Leuprolide provides a medical castration for the patient and deprives hormonally-dependent tumors of testosterone or estrogen. During short-term or intermittent therapy, leuprolide has the same stimulatory action as GnRH, but long-term therapy suppresses gonadotropin release from the pituitary gland and reduces steroidogenesis in the ovaries and testicles. Normally, GnRH is released in a pulsatile fashion, but the sustained activity of leuprolide leads to downregulation of the receptor and decreased production of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). In the male, this activity stops testosterone production in the testis. In the female, it stops estrogen production in the ovaries. In patients with endometriosis, this reversible hypoestrogenic state produces symptomatic relief of the pain of endometriosis and decreases the number of endometriotic lesions. Initially, there is a surge of FSH and LH, which can cause a flare reaction in prostate or breast carcinoma. Eventually, the flare reaction will diminish. Total castration can be expected in 1—2 weeks.
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Initial stimulation of gonadotropins form the anterior pituitary is followed by prolonged suppression. Gonadotropin release from the anterior pituitary transiently increases estrone and estradiol concentrations in females. However, continuous administration of leuprolide in the treatment of endometriosis produces a fall in estrogens to postmenopausal levels. As a consequence of suppression of ovarian function, both normal and ectopic endometrial tissues become inactive and atrophic. As a result, amenorrhea occurs.
Indications of Leuprorelin
- Female infertility
- Precocious puberty
- Breast cancer, adjuvant
- Endometriosis
- Hirsutism
- Prostate cancer
- Uterine fibroids
- Uterine leiomyomata
- Advanced prostate cancer
- Cancer, Breast
- Central precocious puberty
- Endometriosis
- Infertilities
- Paraphilia
- Uterine Leiomyomas
- Symptom recurrence
- Treatment of prostate cancer, endometriosis, uterine fibroids, and premature puberty
- Treatment of congenital hypogonadotropic hypogonadism
- Leuprolide is indicated for the palliative treatment of advanced prostatic cancer, especially as an alternative to orchiectomy or estrogen administration.
- Leuprolide is indicated for the management of endometriosis, including pain relief and reduction of endometriotic lesions.
Contra-Indications of Leuprorelin
- Spread of cancer to the spinal column
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- High cholesterol
- Low amount of magnesium in the blood
- Low amount of potassium in the blood
- Overweight
- Depression
- High blood pressure
- Heart attack
- prolonged QT interval on EKG
- Chronic heart Failure
- Abnormal EKG with QT changes from Birth
- Stroke
- Liver Problems
- Decreased calcification or density of bone
- Seizures
- High blood sugar
- Pregnancy
- A Mother who is producing milk and breastfeeding
- Obstruction of any part of the urinary tract
- Tobacco smoking
- Increased cardiovascular event risk
Dosages of Leuprorelin
Strengths: 22.5 mg/3 months; 7.5 mg/month; 45 mg/6 months; 30 mg/4 months; 65 mg; 11.25 mg/month; 15 mg/month; 3.75 mg/month; 11.25 mg/3 months; 30 mg/3 months; 5 mg/mL; 1 mg/0.2 mL; 7.5 mg; 3.75 mg
Prostate Cancer
- 1 mg injection subcutaneously once a day or
- 7.5 mg depot IM or depot subcutaneously once a month or
- 22.5 mg depot IM once every 3 months or
- 30 mg depot IM once every 4 months or
- 45 mg subcutaneous injection every 6 months or
- 65 mg subcutaneous implant once every 12 month
Endometriosis
- 3.75 mg IM once a month for up to 6 months or 11.25 mg depot every 3 months
Uterine Leiomyomata
- 3.75 mg IM once a month for up to 6 months or 11.25 mg depot every 3 months
Pediatric Precocious Puberty
Depot injection
- Body weight: Less than or equal to 25 kg: 7.5 mg IM once a month
- Body weight: Greater than 25 kg to 37.5 kg: 11.25 mg IM once a month
- Body weight: Greater than 37.5 kg: 15 mg IM once a month
Uterine fibroids
- Adult: As depot preparations: In combination with iron therapy for women with anaemia due to uterine fibroids, 3.75 mg every mth given as a single IM/SC inj or 11.25 mg every 3 mth as IM Inj. Treatment duration: Usually up to 3 mth.
Precocious puberty
- As aqueous soln inj: Initial: 50 mcg/kg daily by SC inj, may be titrated upwards by 10 mcg/kg/day if total down-regulation is not achieved.
- As depot preparations: Initial: 0.3 mg/kg/dose (minimum dose: 7.5 mg) given every 4 wk via IM inj; which equates to children ≤25 kg: 7.5 mg; >25-37.5 kg: 11.25 mg and >37.5 kg: 15 mg given every 4 wk.
- Maintenance: May titrate dose upwards in steps of 3.75 mg every 4 wk if down-regulation is not achieved. Consider discontinuing therapy before age 11 (females) and age 12 (males).
Side Effects of Leuprorelin
The most common
- chest pain
- anxiety
- irregular heartbeat
- certainly hair loss
- headache
- joint painPain
- dizziness
- nausea and vomiting
- Severe stomach ache
- epigastric pain,
- diarrhoea,
- anorexia,
- flatulence,
- headache,
- dizziness,
- fainting, fast or pounding heartbeats.
More common
- Fast or irregular heartbeat
- appetite loss
- changes in nails
- constipation
- fatigue
- fever
- Back pain
- dizziness
- headache
- increased cough
- Acid or sour stomach
- decreased appetite
- Agitation
- chest congestion
- chest pain
- cold sweats
- confusion
- decreased sexual ability or desire
- stomach or abdominal cramps, gas, or pain
- trouble sleeping
Less common
- bleeding gums
- blood in the urine or stools
- chest pain
- diarrhea
- Burning, crawling, itching, numbness, prickling, “pins and needles“, or tingling feelings
- difficulty in moving
- muscle stiffness
- redness of the face, neck, arms and occasionally, upper chest
- lack or loss of strength
- muscle spasm
- difficult or labored breathing
- dry mouth
- headache
- irritability
- lack or loss of strength
- loose stools
- loss of interest or pleasure
- muscle stiffness
- night sweats
- passing gas
- stomach discomfort, upset, or pain
- swollen joints
- trouble concentrating
- increased blood pressure
Drug Interactions of Leuprorelin
Leuprolide may interact with following drugs, supplements & may decrease the efficacy of the drug
- alpha blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin)
- anticancer medications (e.g., cabazitaxel, docetaxel, doxorubicin, etoposide, ifosfamide, irinotecan, vincristine)
- “azole” antifungal medications (e.g., fluconazole, itraconazole, ketoconazole)
- beta-blockers (e.g., atenolol, propranolol, metoprolol)
- barbiturates (e.g., butalbital, pentobarbital, phenobarbital)
- benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)
- calcium channel blockers (e.g., nifedipine, diltiazem, verapamil, amlodipine, felodipine)
- bupropion
- estrogen and estrogen-containing birth control (women)
- medications that promote loss of bone density (e.g., prednisone)
- testosterone and androgens (men)
- corticosteroids (e.g., dexamethasone, prednisone, methylprednisolone)
- cyclosporine
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- losartan
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- metronidazole
- montelukast
- norfloxacin
- ondansetron
- carbamazepine
- phenytoin
- proton pump inhibitors (PPIs; e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine,paroxetine, sertraline)
- sildenafil
- “statin” anticholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
- tadalafil
- tamoxifen
- tetracycline
- theophylline
- tocilizumab
- tolterodine
- tramadol
- other selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, sertraline)
- 5-HT3 antagonists (e.g., granisetron, ondansetron)
- tamsulosin
- tapentadol
- thiazide diuretics (e.g., hydrochlorothiazide, indapamide)
- tramadol
- tricyclic antidepressants (e.g., nortriptyline, amitriptyline, imipramine,
- trimethoprim
- other tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib, sunitinib)
- tetracycline
- tocilizumab
Pregnancy & Lactation of Leuprorelin
FDA Pregnancy Category X
Pregnancy
Leuprolide should not be used during pregnancy. A non-hormonal method of birth control (e.g., condom, diaphragm, IUD) should be used during treatment. If you become pregnant during treatment, notify your doctor as soon as possible.
Lactation
It is not known if leuprolide passes into breast milk. Women should not breast-feed while receiving leuprolide treatment due to risk of harm to the infant.
References
