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Special Alerts
GnRH Agonists: Canadian Labeling Updated to Include Increased Risk of Cardiovascular Disease in Males
September 2011
Health Canada has issued notice to Canadian healthcare professionals and patients that the product labeling for Gonadotropin-Releasing Hormone (GnRH) agonists (eg, goserelin, leuprolide, buserelin, triptorelin, histrelin) has been updated with warnings regarding possible increased risks for cardiovascular events (eg, MI, stroke) in males receiving GnRH agonist therapy for prostate cancer. Although the risk for adverse events appears to be low, healthcare providers are advised to weigh known benefits/risks of GnRH agonists and patient risk factors prior to initiating therapy and to carefully monitor for signs/symptoms of cardiovascular disease during therapy. Patients should be advised to continue with therapy until discussing treatment options with their healthcare provider.
The U.S. prescribing information for these agents has been previously updated with this information.
Further information may be found at
U.S.: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm230334.htm
Canada: http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2011/2011_122-eng.php
Pronunciation
(loo PROE lide)
Generic Available (U.S.)
Yes: Injection (solution)
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Palliative treatment of advanced prostate cancer; management of endometriosis; treatment of anemia caused by uterine leiomyomata (fibroids); central precocious puberty
Use: Unlabeled
Treatment of breast cancer; infertility
Pregnancy Risk Factor
X
Pregnancy Considerations
Pregnancy must be excluded prior to the start of treatment. Although leuprolide usually inhibits ovulation and stops menstruation, contraception is not ensured and a nonhormonal contraceptive should be used. Fetal abnormalities and increased fetal mortality have been noted in animal studies.
Lactation
Excretion in breast milk unknown/contraindicated
Contraindications
Hypersensitivity to leuprolide, GnRH, GnRH-agonist analogs, or any component of the formulation; undiagnosed abnormal vaginal bleeding; pregnancy; breast-feeding
Lupron Depot® 22.5 mg, 30 mg, and 45 mg are also not indicated for use in women
Warnings/Precautions
Special handling:
• Hazardous agent: Use appropriate precautions for handling and disposal.
Concerns related to adverse effects:
• Abnormal menses: Females treated for precocious puberty may experience menses or spotting during the first 2 months of treatment; notify healthcare provider if bleeding continues after the second month.
• Cardiovascular disease: Androgen-deprivation therapy (ADT) may increase the risk for cardiovascular disease (Levine, 2010). Sudden cardiac death and stroke have been reported in men receiving GnRH agonists. Long-term ADT may prolong the QT interval; consider the benefits of ADT versus the risk for QT prolongation in patients with a history of QTc prolongation, with medications known to prolong the QT interval, or with pre-existing cardiac disease.
• Decreased bone density: Has been reported when used for ≥6 months. Use caution in patients with additional risk factors for bone loss (eg, chronic alcohol use, corticosteroid therapy).
• Endometriosis: Exacerbation of endometriosis or uterine leiomyomata may occur initially.
• Hyperglycemia: Diabetes and/or worsening of glycemic control have been reported in men receiving GnRH agonists.
• Pituitary apoplexy: Rare cases of pituitary apoplexy (frequently secondary to pituitary adenoma) have been observed with leuprolide administration (onset from 1 hour to usually <2 weeks); may present as sudden headache, vomiting, visual or mental status changes, and infrequently cardiovascular collapse; immediate medical attention required.
• Spinal cord compression: Has been reported when used for prostate cancer; closely observe patients for weakness and paresthesias in first few weeks of therapy. Observe patients with metastatic vertebral lesions closely.
• Tumor flare: Transient increases in testosterone (~50% above baseline) can lead to tumor flare, bone pain, hematuria, bladder outlet obstruction and neuropathy in prostate cancer patients during the first few weeks of therapy.
• Urinary tract obstruction: Has been reported when used for prostate cancer; closely observe patients for urinary tract obstruction and hematuria in first few weeks of therapy. Observe patients with urinary obstruction closely.
Disease-related concerns:
• Prostate cancer: Androgen deprivation therapy may increase the risk for cardiovascular disease, diabetes, insulin resistance, obesity, alterations in lipids, and fractures.
• Psychiatric illness: Use with caution in patients with a history of psychiatric illness; alteration in mood, memory impairment, and depression have been associated with use.
Dosage form specific issues:
• Benzyl alcohol: Some dosage forms may contain benzyl alcohol which has been associated with “gasping syndrome” in neonates. Patients with benzyl alcohol allergy may demonstrate a hypersensitivity reaction (usually local) in the form of erythema and induration at the injection site.
• Depot formulations: Vehicle used in injectable (polylactide-co-glycolide microspheres) has rarely been associated with retinal artery occlusion in patients with abnormal arteriovenous anastomosis (eg, patent foramen ovale). Due to different release properties, combinations of dosage forms or fractions of dosage forms should not be interchanged.
Adverse Reactions
Children (percentages based on 1-month and 3-month pediatric formulations combined):
>10%: Local: Injection site pain (≤20%)
2% to 10%:
Cardiovascular: Vasodilation (2%)
Central nervous system: Emotional lability (5%), mood altered (5%), headache (3% to 5%), pain (3%)
Dermatologic: Acne (3%), rash (3% including erythema multiforme), seborrhea (3%)
Gastrointestinal: Weight gain (≤7%)
Genitourinary: Vaginal bleeding (3%), vaginal discharge (3%), vaginitis (3%)
Local: Injection site reaction (≤9%)
<2%: Allergic reaction, alopecia, appetite decreased/increased, arthralgia, asthma, body odor, bradycardia, cervix disorder, constipation, cough, crying, depression, dizziness, dysmenorrhea, dyspepsia, dysphagia, epistaxis, extremity pain, feminization, fever, flu-like syndrome, gait disturbance, gingivitis, goiter, growth retarded, gynecomastia, hirsutism, hyperhidrosis, hyperkinesias, hypertension, infection, leukoderma, musculoskeletal pain, myalgia, myopathy, nausea, nervousness, obesity, pallor, peripheral edema, personality disorder, pharyngitis, purpura, rhinitis, sexual maturity accelerated, sinusitis, skin striae, somnolence, syncope, tearfulness, urinary incontinence, vision decreased, vomiting, weakness
Adults:
Note: For prostate cancer treatment, an initial rise in serum testosterone concentrations may cause “tumor flare” or worsening of symptoms, including bone pain, neuropathy, hematuria, or ureteral or bladder outlet obstruction during the first 2 weeks. Similarly, an initial increase in estradiol levels, with a temporary worsening of symptoms, may occur in women treated with leuprolide.
Delayed release formulations:
>10%:
Cardiovascular: Edema (≤14%)
Central nervous system: Headache (≤65%), pain (<2% to 33%), depression (≤31%), insomnia (≤31%), fatigue (≤17%), dizziness/vertigo (≤16%)
Dermatologic: Skin reaction (≤12%)
Endocrine & metabolic: Hot flashes (25% to 98%), testicular atrophy (≤20%), hyperlipidemia (≤12%), libido decreased (≤11%)
Gastrointestinal: Nausea/vomiting (≤25%), bowel function altered (≤14%), weight gain/loss (≤13%)
Genitourinary: Vaginitis (11% to 28%), urinary disorder (13% to 15%)
Local: Injection site burning/stinging (transient: ≤35%)
Neuromuscular & skeletal: Weakness (≤18%), joint disorder (≤12%)
Miscellaneous: Flu-like syndrome (≤12%)
1% to 10% (limited to important or life-threatening):
Cardiovascular: Angina (<5%), arrhythmia (<5%), atrial fibrillation (<5%), bradycardia (<5%), CHF (<5%), deep thrombophlebitis (<5%), hyper-/hypotension (<5%), palpitation (<5%), syncope (<5%), tachycardia (<5%)
Central nervous system: Nervousness (≤8%), anxiety (≤6%), confusion (<5%), delusions (<5%), dementia (<5%), fever (<5%), seizure (<5%)
Dermatologic: Acne (≤10%), alopecia (≤5%), bruising (≤5%), cellulitis (<5%), pruritus (≤3%), rash (≤2%), hirsutism (<2%)
Endocrine & metabolic: Dehydration (≤8%), gynecomastia (≤7%), breast tenderness/pain (≤6%), bicarbonate decreased (≥5%), hyper-/hypocholesterolemia (≥5%), hyperglycemia (≥5%), hyperphosphatemia (≥5%), hyperuricemia (≥5%), hypoalbuminemia (≥5%), hypoproteinemia (≥5%), lactation (<5%), testicular pain (≤4%), menstrual disorder (≤2%)
Gastrointestinal: Dysphagia (<5%), gastrointestinal hemorrhage (<5%), intestinal obstruction (<5%), ulcer (<5%), constipation (≤3%), gastroenteritis/colitis (≤3%), diarrhea (≤2%)
Genitourinary: Prostatic acid phosphatase increased/decreased (≥5%), urine specific gravity increased/decreased (≥5%), impotence (≤5%), balanitis (<5%), incontinence (<5%), penile/testis disorder (<5%), urinary tract infection (<5%), nocturia (≤4%), polyuria (2% to 4%), dysuria (≤2%), bladder spasm (<2%), erectile dysfunction (<2%), hematuria (<2%), urinary retention (<2%), urinary urgency (<2%)
Hematologic: Eosinophilia (≥5%), leukopenia (≥5%), platelets increased (≥5%), anemia
Hepatic: Liver function tests abnormal (≥5%), partial thromboplastin time increased (≥5%), prothrombin time increased (≥5%), hepatomegaly (<5%)
Local: Injection site pain (2% to 5%), injection site erythema (1% to 3%)
Neuromuscular & skeletal: Myalgia (≤8%), paresthesia (≤8%), neuropathy (<5%), paralysis (<5%), pathologic fracture (<5%), bone pain (<2%), arthralgia (≤1%)
Renal: BUN increased (≥5%), creatinine increased (≥5%)
Respiratory: Emphysema (<5%), epistaxis (<5%), hemoptysis (<5%), pleural effusion (<5%), pulmonary edema (<5%), dyspnea (≤2%), cough (≤1%)
Miscellaneous: Diaphoresis (≤5%), allergic reaction (<5%), infection (5%), lymphadenopathy (<5%)
Immediate release formulation:
>10%:
Cardiovascular: ECG changes/ischemia (19%), peripheral edema (12%)
Central nervous system: Pain (13%)
Endocrine & metabolic: Hot flashes (55%)
1% to 10% (limited to important or life-threatening):
Cardiovascular: Hypertension (8%), murmur (3%), thrombosis/phlebitis (2%), CHF (1%), angina, arrhythmia, MI, syncope
Central nervous system: Headache (7%), insomnia (7%), dizziness/lightheadedness (5%), anxiety, depression, fatigue, fever, nervousness
Dermatologic: Dermatitis (5%), alopecia, bruising, itching, lesions, pigmentation
Endocrine & metabolic: Gynecomastia/breast tenderness/pain (7%), testicular size decreased (7%), diabetes, hypercalcemia, hypoglycemia, libido decreased, thyroid enlarged
Gastrointestinal: Constipation (7%), anorexia (6%), nausea/vomiting (5%), diarrhea, dysphagia, gastrointestinal bleeding, peptic ulcer, rectal polyps
Genitourinary: Urinary frequency/urgency (6%), impotence (4%), urinary tract infection (3%), bladder spasm, dysuria, incontinence, testicular pain, urinary obstruction
Hematologic: Anemia (5%)
Local: Injection site reaction
Neuromuscular & skeletal: Weakness (10%), bone pain (5%), peripheral neuropathy
Ocular: Blurred vision
Renal: Hematuria (6%), BUN increased, creatinine increased
Respiratory: Dyspnea (2%), cough, pneumonia, pulmonary embolus, pulmonary fibrosis
Miscellaneous: Infection, inflammation
Children and Adults: Any formulations: Postmarketing and/or case reports: Abdominal pain, anaphylactic/anaphylactoid reactions, asthmatic reactions, bone density decreased, coronary artery disease, diabetes; fibromyalgia-like symptoms (arthralgia/myalgia, headaches, GI distress); flushing, hemoptysis, hepatic dysfunction, hypokalemia, hypoproteinemia, injection site induration/abscess, liver injury, MI, pelvic fibrosis, penile swelling, peripheral neuropathy, photosensitivity; pituitary apoplexy (cardiovascular collapse, mental status altered, ophthalmoplegia, sudden headache, visual changes, vomiting); prostate pain, pulmonary embolism, pulmonary infiltrate, seizure, spinal fracture/paralysis, stroke, suicidal ideation/attempt (rare), tenosynovitis-like symptoms, thrombocytopenia, transient ischemic attack, uric acid increased, urticaria, WBC decreased/increased
Metabolism/Transport Effects
None known.
Drug Interactions
Antidiabetic Agents: Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Storage
Eligard®: Store at 2°C to 8°C (36°F to 46°C). Allow to reach room temperature prior to using; once mixed, must be administered within 30 minutes.
Lupron Depot®, Lupron Depot-Ped®: Store at room temperature of 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Upon reconstitution, the suspension does not contain a preservative and should be used immediately; discard if not used within 2 hours.
Leuprolide acetate 5 mg/mL solution: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light and store vial in carton until use. Do not freeze.
Reconstitution
Eligard®: Packaged in two syringes; one contains the Atrigel® polymer system and the second contains leuprolide acetate powder; follow package instructions for mixing
Lupron Depot®, Lupron Depot-Ped®: Reconstitute only with diluent provided
Mechanism of Action
Leuprolide, is an agonist of luteinizing hormone-releasing hormone (LHRH). Acting as a potent inhibitor of gonadotropin secretion; continuous administration results in suppression of ovarian and testicular steroidogenesis due to decreased levels of LH and FSH with subsequent decrease in testosterone (male) and estrogen (female) levels. In males, testosterone levels are reduced to below castrate levels. Leuprolide may also have a direct inhibitory effect on the testes, and act by a different mechanism not directly related to reduction in serum testosterone.
Pharmacodynamics/Kinetics
Onset of action: Following transient increase, testosterone suppression occurs in ~2-4 weeks of continued therapy
Distribution: Males: Vd: 27 L
Protein binding: 43% to 49%
Metabolism: Major metabolite, pentapeptide (M-1)
Bioavailability: SubQ: 94%
Excretion: Urine (<5% as parent and major metabolite)
Dosage
Children: Precocious puberty (consider discontinuing by age 11 for females and by age 12 for males):
I.M.:
Lupron Depot-Ped® (monthly):
≤25 kg: 7.5 mg every month
>25-37.5 kg: 11.25 mg every month
>37.5 kg: 15 mg every month
Titrate dose upward in increments of 3.75 mg every 4 weeks if down-regulation is not achieved.
Lupron Depot-Ped® (3 month): 11.25 mg or 30 mg every 12 weeks
SubQ (leuprolide acetate 5 mg/mL solution): Initial: 50 mcg/kg/day; titrate dose upward by 10 mcg/kg/day if down-regulation is not achieved. Note: Higher mg/kg doses may be required in younger children.
Adults:
Prostate cancer, advanced:
I.M.:
Lupron Depot® 7.5 mg (monthly): 7.5 mg every month or
Lupron Depot® 22.5 mg (3 month): 22.5 mg every 12 weeks or
Lupron Depot® 30 mg (4 month): 30 mg every 16 weeks or
Lupron Depot® 45 mg (6 month): 45 mg every 24 weeks
SubQ:
Eligard®: 7.5 mg monthly or 22.5 mg every 3 months or 30 mg every 4 months or 45 mg every 6 months
Leuprolide acetate 5 mg/mL solution: 1 mg/day
Endometriosis: I.M.: Initial therapy may be with leuprolide alone or in combination with norethindrone; if retreatment for an additional 6 months is necessary, concomitant norethindrone should be used. Retreatment is not recommended for longer than one additional 6-month course.
Lupron Depot®: 3.75 mg every month for up to 6 months or
Lupron Depot®-3 month: 11.25 mg every 3 months for up to 2 doses (6 months total duration of treatment)
Uterine leiomyomata (fibroids): I.M. (in combination with iron):
Lupron Depot®: 3.75 mg every month for up to 3 months or
Lupron Depot®-3 month: 11.25 mg as a single injection
Breast cancer, premenopausal ovarian ablation (unlabeled use): I.M.:
Lupron Depot®: 3.75 mg every 28 days for up to 24 months (Boccardo, 1999) or
Lupron Depot®-3 month: 11.25 mg every 3 months for up to 24 months (Boccardo, 1999; Schmid, 2007)
Dosage: Combination Regimens
Prostate cancer:
Bicalutamide-Leuprolide
FL
Administration: I.M.
Lupron Depot®, Lupron Depot-Ped®: Administer as a single injection. Vary injection site periodically
Administration: Other
SubQ:
Eligard®: Vary injection site; choose site with adequate subcutaneous tissue (eg, upper or mid-abdomen, upper buttocks); avoid areas that may be compressed or rubbed (eg, belt or waistband)
Leuprolide acetate 5 mg/mL solution: Vary injection site; if an alternate syringe from the syringe provided is required, insulin syringes should be used
Monitoring Parameters
Bone mineral density
Precocious puberty: GnRH testing (blood LH and FSH levels), measurement of height and bone age every 6-12 months, testosterone in males and estradiol in females (I.M. [monthly] and SubQ formulations: 1-2 months after initiation of therapy or with dosage change; I.M. [3 month] formulation: 2-3 months after initiation of therapy, month 6, and as clinically indicated thereafter); Tanner staging
Prostatic cancer: LH and FSH levels, serum testosterone (~4 weeks after initiation of therapy), PSA; weakness, paresthesias, and urinary tract obstruction in first few weeks of therapy. Screen for diabetes (blood glucose and Hb A1c) and cardiovascular risk prior to initiating and periodically during treatment.
Test Interactions
Interferes with pituitary gonadotropic and gonadal function tests during and up to 3 months after monthly administration of leuprolide therapy.
Patient Education
This medication may be administered on a regular schedule; keep all appointments. If you have diabetes, monitor blood sugar frequently; can cause alteration in glycemic control. You may experience disease flare (increased bone pain) and urinary retention during early treatment (usually resolves); dizziness, headache, lethargy, or faintness; nausea or vomiting; constipation; hot flashes or flushing; breast swelling or tenderness; or decreased libido or impotence. Instruct patient to notify prescriber of chest pain; swelling of extremities; difficulty urinating; CNS changes (change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or blurred eyesight); behavioral changes, such as depression, mood swings, or insomnia; severe headache; menstruation over 2 months; severe nausea or vomiting; increase in bone pain after 2-4 weeks of care; severe back pain; feeling very tired or weak; or increased thirst, weight loss, or urination.
Geriatric Considerations
No dosage adjustments are needed in the elderly. Monitoring for bone density changes, serum lipid, hemoglobin A1c, blood pressure, and serum calcium changes is recommended.
Additional Information
Eligard® Atrigel®: A nongelatin-based, biodegradable, polymer matrix
Oncology Comment: Guidelines from the American Society of Clinical Oncology (ASCO) for hormonal management of advanced prostate cancer which is androgen-sensitive (Loblaw, 2007) recommend either orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonists as initial treatment for androgen deprivation.
Anesthesia and Critical Care Concerns/Other Considerations
Eligard® is a nongelatin-based, biodegradable, polymer matrix.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Gum hemorrhage, gingivitis, dry mucous membranes, and dysphagia.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause alteration in mood or memory impairment. Depression, insomnia, and dizziness are common; may also cause anxiety, nervousness, confusion, or delusions
Mental Health: Effects on Psychiatric Treatment
None reported; however, response to psychotropic agents may be altered given the effects on mental status
Nursing: Physical Assessment/Monitoring
Assess carefully for use-related cautions prior to therapy. If self-administered, teach patient or caregiver proper storage, injection technique, and syringe/needle disposal. Wash hands before and after injection. Monitor patients for development of diabetes; manage cardiovascular risk factors.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as acetate [depot formulation, preservative free]:
Eligard®: 7.5 mg (monthly), 22.5 mg (3 month), 30 mg (4 month), 45 mg (6 month) [contains polylactide-co-glycolide; supplied with diluent]
Lupron Depot-Ped®: 7.5 mg (monthly), 11.25 mg (3 month), 11.25 mg (monthly), 15 mg (monthly), 30 mg (3 month) [contains polylactide-co-glycolide, polysorbate 80]
Lupron Depot®: 3.75 mg (monthly), 7.5 mg (monthly), 11.25 mg (3 month), 22.5 mg (3 month), 30 mg (4 month), 45 mg (6 month) [contains polylactide-co-glycolide, polysorbate 80]
Injection, solution, as acetate: 5 mg/mL (2.8 mL)
Pricing: U.S. (www.drugstore.com)
Kit (Lupron Depot)
3.75 mg (1): $720.98
7.5 mg (1): $927.00
11.25 mg (1): $2208.91
22.5 mg (1): $2756.06
30 mg (1): $3394.87
Kit (Lupron Depot-Ped)
7.5 mg (1): $960.04
References
Adjuvant Breast Cancer Trials Collaborative Group, “Ovarian Ablation or Suppression in Premenopausal Early Breast Cancer: Results From the International Adjuvant Breast Cancer Ovarian Ablation or Suppression Randomized Trial,” J Natl Cancer Inst, 2007, 99(7):516-25.
Boccardo F, Rubagotti A, Amoroso D, et al, “Endocrinological and Clinical Evaluation of Two Depot Formulations of Leuprolide Acetate in Pre- and Perimenopausal Breast Cancer Patients,” Cancer Chemother Pharmacol, 1999, 43(6):461-6.
Crawford ED, Eisenberger MA, McLeod DG, et al, “A Controlled Trial of Leuprolide With and Without Flutamide in Prostatic Carcinoma,” N Engl J Med, 1989, 321(7):419-24.
Kappy MS, Stuart T, and Perelman A, “Efficacy of Leuprolide Therapy in Children With Central Precocious Puberty,” Am J Dis Child, 1988, 142(10):1061-4.
Keating NL, O'Malley AJ, and Smith MR, “Diabetes and Cardiovascular Disease During Androgen Deprivation Therapy for Prostate Cancer,” J Clin Oncol, 2006, 24(27):4448-56.
Lee PA and Page JG, “Effects of Leuprolide in the Treatment of Central Precocious Puberty,” J Pediatr, 1989, 114(2):321-4.
Levine GN, D'Amico AV, Berger P, et al, “Androgen-Deprivation Therapy in Prostate Cancer and Cardiovascular Risk. A Science Advisory from the American Heart Association, American Cancer Society, and American Urological Association,” Circulation, 2010, 121:831-38.
Loblaw DA, Virgo KS, Nam R, et al, “Initial Hormonal Management of Androgen-Sensitive Metastatic, Recurrent, or Progressive Prostate Cancer: 2006 Update of an American Society of Clinical Oncology Practice Guideline,” J Clin Oncol, 2007, 25(12):1596-605.
Plosker GL and Brogden RN, “Leuprorelin. A Review of Its Pharmacology and Therapeutic Use in Prostate Cancer, Endometriosis and Other Sex Hormone-Related Disorders,” Drugs, 1994, 48(6):930-67.
Schmid P, Untch M, Kossé V, et al, “Leuprorelin Acetate Every-3-Months Depot versus Cyclophosphamide, Methotrexate, and Fluorouracil as Adjuvant Treatment in Premenopausal Patients With Node-Positive Breast Cancer: the TABLE Study,” J Clin Oncol, 2007, 25(18):2509-15.
Schmid P, Untch M, Wallwiener D, et al, “Cyclophosphamide, Methotrexate and Fluorouracil (CMF) Versus Hormonal Ablation With Leuprorelin Acetate as Adjuvant Treatment of Node-Positive, Premenopausal Breast Cancer Patients: Preliminary Results of the TABLE-Study (Takeda Adjuvant Breast Cancer Study With Leuprorelin Acetate),” Anticancer Res, 2002, 22(4):2325-32.
Spry NA, Galvão DA, Davies R, et al, “Long-Term Effects of Intermittent Androgen Suppression on Testosterone Recovery and Bone Mineral Density: Results of a 33-Month Observational Study,” BJU Int, 2009, 104(6):806-12.
Tanaka T, Niimi H, Matsuo N, et al, “Results of Long-Term Follow-Up After Treatment of Central Precocious Puberty With Leuprorelin Acetate: Evaluation of Effectiveness of Treatment and Recovery of Gonadal Function. The TAP-144-SR Japanese Study Group on Central Precocious Puberty,” J Clin Endocrinol Metab, 2005, 90(3):1371-6.
Tang J, and Weiter JJ, “Branch Retinal Artery Occlusion After Injection of a Long-Acting Risperidone Preparation,” Annals Intern Med, 2007, 147(4): 283-3.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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