Leuproreline Lutrate Depot
Leuproreline Lutrate Depot Uses, Dosage, Side Effects, Food Interaction and all others data.
Leuprorelin is a gonadotropin-releasing hormone (GnRH) analogue. Following an initial stimulation of gonadotrophins, continuous admin of Leuprorelin leads to down regulation of GnRH receptors and subsequently reduces pituitary gonadotrophin secretion. Reduced gonadotrophin levels lead to inhibition of sex hormone (testosterone and oestrogen) production. Within 2-4 wk after treatment initiation, testosterone levels in male may be reduced to below castrate threshold.
Leuproreline Lutrate Depot is a gonadotropin-releasing hormone (GnRH) analogue that functions as a GnRH receptor superagonist. After an initial spike in GnRH-mediated steroidal production, including testosterone and estradiol, prolonged use results in a significant drop in circulating steroid levels, in line with those produced through other forms of androgen-deprivation therapy (ADT). The corresponding hormonal/steroidal changes produce specific adverse effects in different patient populations.
In women undergoing treatment for endometriosis or uterine leiomyomata, careful consideration regarding pregnancy status is advised. The initial increase in estradiol levels may worsen symptoms such as pain and bleeding. Long-term use of leuprolide is associated with loss of bone mineral density. Patients co-administered with norethisterone may experience sudden vision loss, proptosis, diplopia, migraine, thrombophlebitis, and pulmonary embolism and may also be at higher risk of cardiovascular disease. Patients with a history of depression may experience severe recurrence of depressive symptoms.
In men undergoing palliative treatment for advanced/metastatic prostate cancer, short-term spikes in testosterone levels may cause tumour flare and associated symptoms such as bone pain, hematuria, neuropathy, bladder and/or ureteral obstruction, and spinal cord compression. In addition, patients are at increased risk of developing hyperglycemia, diabetes, and cardiovascular disease, which may manifest through myocardial infarction, stroke, cardiac death, or prolonged QT/QTc interval. In addition, Leuproreline Lutrate Depot may cause convulsions and embryo-fetal toxicity.
| Trade Name | Leuproreline Lutrate Depot |
| Availability | Prescription only |
| Generic | Leuprolide |
| Leuprolide Other Names | Leuprorelin, Leuprorelina, Leuproreline, Leuprorelinum |
| Related Drugs | Supprelin LA, estradiol, tamoxifen, Premarin, Lupron, norethindrone, medroxyprogesterone, Xtandi, Provera, Sprintec |
| Type | |
| Formula | C59H84N16O12 |
| Weight | Average: 1209.3983 Monoisotopic: 1208.645462232 |
| Protein binding | Leuprolide displays in vitro binding to human plasma proteins between 43% and 49%. |
| Groups | Approved, Investigational |
| Therapeutic Class | Drugs acting on the Uterus, Drugs affecting (inhibiting) gonadotrophin |
| Manufacturer | |
| Available Country | Netherlands |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
For treatment of prostate cancer, endometriosis, uterine fibroids and premature puberty
Leuproreline Lutrate Depot is also used to associated treatment for these conditions: Advanced Prostate Cancer, Anemia, Central Precocious Puberty (CPP), Endometriosis
How Leuproreline Lutrate Depot works
Gonadotropin-releasing hormone (GnRH) is a naturally occurring decapeptide that modulates the hypothalamic-pituitary-gonadal (HPG) axis. GnRH binds to corresponding receptors (GnRHRs) on the anterior pituitary gonadotropes, which in turn release luteinizing hormone (LH) and follicle-stimulating hormone (FSH); these, in turn, affect the downstream synthesis and release of the sex hormones testosterone, dihydrotestosterone, estrone, and estradiol.
Despite the variety of conditions indicated for treatment with leuprolide, the mechanism of action underlying efficacy is the same in all cases. As a GnRHR agonist, leuprolide binds to and initially activates downstream LH and FSH release; this initial spike in gonadotropin levels is responsible for some of the adverse effects associated with treatment. After 2-4 weeks of treatment, continuous stimulation of GnRHR results in feedback inhibition and significant downregulation of LH, FSH, and their corresponding downstream effects, producing a therapeutic benefit. These effects are reversible upon treatment discontinuation.
Dosage
Leuproreline Lutrate Depot dosage
Adult:Palliative treatment of advanced prostate cancer:1 mg as single daily dose by SC inj. Depot preparations may be given by IM or SC route, dosage and route may differ between different brands and countries. In the UK: As depot preparations: 3.75 mg every mth as single IM/SC inj; or 11.25 mg every 3 mth via SC inj. In the US: As depot preparations: 7.5 mg every mth, or 22.5 mg every 3 mth, or 30 mg every 4 mth via IM/SC inj depending on the preparations; or 45 mg every 6 mth via SC inj.
Endometriosis:As depot preparations: 3.75 mg every mth given as a single IM/SC inj or 11.25 mg every 3 mth as IM depot Inj. Initiate treatment during the 1st 5 days of menstrual cycle up to 6 mth. May be used with norethindrone acetate 5 mg daily for initial management of endometriosis and for management of recurrence symptoms. Duration of retreatment: Should not exceed one additional 6 mth course.
Uterine fibroids: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.
Preparation for intrauterine surgery:Endometrial preparation prior to intrauterine surgery: As depot preparations: 3.75 mg as a single inj via IM/SC given 5-6 wk before the procedure; therapy should be initiated during days 3-5 of the menstrual cycle.
Child: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
Treatment of precocious puberty: General pain, headache, acne, rash, seborrhoea, emotional lability, vaginitis, vaginal bleeding vaginal discharge
Treatment of prostate cancer: Transient worsening of signs and symptoms (usually increase in bone pain), ECG changes, high blood pressure, peripheral oedema, anorexia, constipation, nausea, vomiting, anaemia, myalgia, dizziness, general pain, headache, insomnia or sleep disorder, sinus congestion, urinary frequency/urgency, haematuria, UTI, asthaenia, physiological effects of decreased testosterone (e.g. gynaecomastia, breast tenderness, decreased testicular size, hot flashes, impotence).
Treatment of endometriosis and uterine fibroids treatment: General pain, headache, asthaenia, nausea, vomiting, oedema, weight changes, acne, hirsutism, dizziness, insomnia, sleep disturbance, paraesthesias, skin reactions, effects of hypoestrogenism such as hot flashes, joint disorder, myalgia, decreased libido, depression, emotional lability, nervousness, breast tenderness, vaginitis.
Toxicity
Leuproreline Lutrate Depot is considered extremely safe, with low dose-related toxicity and comparatively mild adverse effects. Prostate cancer patients treated with leuprolide at doses as high as 20 mg/day for two years showed no additional adverse effects compared to those receiving 1 mg/day.
Precaution
Vary inj site periodically. May cause transient elevation of testosterone levels during the first 1-2 wk, which may lead to worsening or onset of new symptoms (e.g. bone pain, neuropathy, haematuria) in prostate cancer patients. Ureteral obstruction and spinal cord compression have been reported; closely monitor patients with urinary obstruction and/or metastatic vertebral lesion. Leuprorelin is associated with increased risk of diabetes and certain CV diseases (heart attack, sudden cardiac death, stroke) when used in men for treatment of prostate cancer. For prostate cancer, monitor response by testosterone and prostate-specific antigen (PSA) levels. For precocious puberty in children, monitor response by GnRH stimulation test sex steroid levels 1-2 month after treatment initiation. Leuprorelin usually inhibits ovulation and stops menstruation in women, but does not incur contraception, non-hormonal contraception should be used as pregnancy is contraindicated. May cause adverse reactions associated with hypoestrogenism and loss in bone density.
Food Interaction
No interactions found.Leuproreline Lutrate Depot Drug Interaction
Unknown: aspirin, aspirin, calcium / vitamin d, calcium / vitamin d, bicalutamide, bicalutamide, tamsulosin, tamsulosin, levothyroxine, levothyroxine, cyanocobalamin, cyanocobalamin, pyridoxine, pyridoxine, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, abiraterone, abiraterone
Leuproreline Lutrate Depot Disease Interaction
Moderate: cardiovascular disease, diabetes, QT interval prolongation, bone mineral density, seizures
Volume of Distribution
Leuproreline Lutrate Depot has an apparent steady-state volume of distribution of 27 L following intravenous bolus administration to healthy males. The volume of distribution for indicated routes of subcutaneous or intramuscular injection has not been reported.
Elimination Route
Leuproreline Lutrate Depot is typically administered as a single-dose long-acting formulation employing either microsphere or biodegradable solid depot technologies. Regardless of the exact formulation and initial dose strength, the Cmax is typically achieved by 4-5 hours post-injection and displays large variability in the range of 4.6 - 212 ng/mL. Eventual steady-state kinetics are typically achieved by four weeks, with a narrower range of 0.1 - 2 ng/mL. No studies on the effects of food on absorption have been carried out.
Half Life
Leuproreline Lutrate Depot has a terminal elimination half-life of approximately three hours.
Clearance
Leuproreline Lutrate Depot administered as a 1 mg intravenous bolus in healthy males has a mean systemic clearance between 7.6 and 8.3 L/h.
Elimination Route
Following administration of 3.75 mg leuprolide depot suspension to three patients, less than 5% of the initial dose was recovered as unchanged or pentapeptide metabolite in the urine.
Pregnancy & Breastfeeding use
Category X: Studies in animals or human beings have demonstrated foetal abnormalities or there is evidence of foetal risk based on human experience or both, and the risk of the use of the drug in pregnant women clearly outweighs any possible benefit. The drug is contraindicated in women who are or may become pregnant.
Contraindication
Pregnancy, lactation; hypersensitivity to GnRH, GnRH agonist analogs or product excipients; undiagnosed abnormal vaginal bleeding.
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