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Special Alerts
GnRH Agonists: Prescribing Information to Include Increased Risk of Diabetes and Cardiovascular Disease - October 2010
In October 2010, the U.S. Food and Drug Administration (FDA) announced that manufacturers of gonadotropin-releasing hormone (GnRH) agonists will be required to update their prescribing information to include the increased risk of diabetes and cardiovascular disease in men receiving these agents for prostate cancer treatment. In May 2010, the FDA issued a notice regarding initiation of a safety review of GnRH agonists (eg, goserelin, leuprolide) for the treatment of prostate cancer and a possible increased risk of diabetes and cardiovascular disease (ie, heart attack, sudden cardiac death, or stroke). The FDA evaluated preliminary data from one randomized, controlled clinical trial and several observational studies. A Science Advisory statement from the American Heart Association, the American Cancer Society, and the American Urological Association was also considered in the evaluation. Some of these studies demonstrated a small, but statistically significant increased risk of diabetes and/or cardiovascular disease in men receiving GnRH agonist therapy versus men receiving alternative therapy for prostate cancer. The decision to update current labeling was based on the Agency's review of these data.
The FDA believes that although the risk for diabetes and cardiovascular disease appears to be low, patients should be evaluated for these risks. Healthcare providers are also encouraged to:
- Follow prescribing recommendations for GnRH agonists
- Carefully weigh known benefits/risks of GnRH agonists when determining appropriate treatment for prostate cancer
- Monitor patients receiving GnRH-agonist therapy for diabetes (periodic blood glucose and/or glycosylated hemoglobin) and signs/symptoms of cardiovascular disease
- Manage cardiovascular risk factors (blood pressure, weight, cholesterol, blood sugar, smoking) according to current clinical practice
Although GnRH agonists may be used in women and children, there are no known comparable studies evaluating this same risk in either of these populations.
Further information may be found at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm230334.htm
Pronunciation
(loo PROE lide)
Generic Available (U.S.)
Yes: Injection (solution)
Index Terms
U.S. Brand Names
Canadian Brand Names
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/Investigational
Treatment of breast cancer; infertility; prostatic hyperplasia
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®-4 month (30 mg) is not indicated for use in women
Eligard® is contraindicated in women and children
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.
• 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.
• 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 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:
• Cardiovascular disease: Androgen-deprivation therapy may increase the risk for cardiovascular disease (Levine, 2010).
• 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.
• 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).
Adverse Reactions
Children:
2% to 10%:
Central nervous system: Pain (2%)
Dermatologic: Acne (2%), rash (2% including erythema multiforme), seborrhea (2%)
Genitourinary: Vaginitis (2%), vaginal bleeding (2%), vaginal discharge (2%)
Local: Injection site reaction (5%)
<2%: Alopecia, body odor, cervix disorder, dysphagia, emotional lability, epistaxis, fever, gingivitis, gynecomastia, headache, nausea, nervousness, peripheral edema, personality disorder, sexual maturity accelerated, skin striae, somnolence, syncope, urinary incontinence, vasodilation, vomiting, weight gain
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%), hirsutism (<2%), rash (<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%), gastroenteritis/colitis (≤3%), diarrhea (≤2%), constipation (≤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%), bladder spasm (<2%), dysuria (<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%)
Renal: BUN increased (≥5%), creatinine increased (≥5%)
Respiratory: Emphysema (<5%), epistaxis (<5%), hemoptysis (<5%), pleural effusion (<5%), pulmonary edema (<5%), dyspnea (≤2%)
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 (limited to important or life-threatening): Anaphylactic/anaphylactoid reactions, asthmatic reactions, bone density decreased; fibromyalgia-like symptoms (arthralgia/myalgia, headaches, GI distress); hemoptysis, hepatic dysfunction, hypokalemia, hypoproteinemia, injection site induration/abscess, MI, pelvic fibrosis, penile swelling, photosensitivity; pituitary apoplexy (cardiovascular collapse, mental status altered, ophthalmoplegia, sudden headache, visual changes, vomiting); prostate pain, pulmonary embolism, pulmonary infiltrate, spinal fracture/paralysis, stroke, tenosynovitis-like symptoms, thrombocytopenia, transient ischemia attack, uric acid increased, urticaria, WBC increased
Drug Interactions
Antidiabetic Agents: Luteinizing Hormone-Releasing Hormone Analogs may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Storage
Lupron®: Lupron®: Store below 25°C (77°F). Protect from light and store vial in carton until use. Do not freeze.
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® may be stored at room temperature of 15°C to 30°C (59°F to 86°F). Upon reconstitution, the suspension does not contain a preservative and should be used immediately.
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®: 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: Oral: None; 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):
SubQ (Lupron®): Initial: 50 mcg/kg/day (per manufacturer, doses of 20-45 mcg/kg/day have also been reported); 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.
I.M. (Lupron Depot-Ped®): 0.3 mg/kg/dose given every 28 days (minimum dose: 7.5 mg)
≤25 kg: 7.5 mg
>25-37.5 kg: 11.25 mg
>37.5 kg: 15 mg
Titrate dose upward in increments of 3.75 mg every 4 weeks if down-regulation is not achieved.
Adults:
Advanced prostate cancer:
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
Lupron®: 1 mg/day
I.M.:
Lupron Depot®: 7.5 mg/dose given monthly (every 28-33 days) or
Lupron Depot®-3: 22.5 mg every 3 months or
Lupron Depot®-4: 30 mg every 4 months
Breast cancer, premenopausal ovarian ablation (unlabeled use; Boccardo, 1999): I.M.:
Lupron Depot®: 3.75 mg every 28 days or
Lupron Depot®-3: 11.25 mg every 3 months
Endometriosis: I.M.: Initial therapy may be with leuprolide alone or in combination with norethindrone; if retreatment for an additional 6 months is necessary, norethindrone should be used. Retreatment is not recommended for longer than one additional 6-month course.
Lupron Depot®: 3.75 mg/month for up to 6 months or
Lupron Depot®-3: 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/month for up to 3 months or
Lupron Depot®-3: 11.25 mg as a single injection
Dosage: Combination Regimens
Prostate cancer:
Bicalutamide-Leuprolide
FL
Administration: I.M.
Lupron Depot®: Vary injection site periodically
Administration: Other
SubQ:
Eligard®: Vary injection site; choose site with adequate subcutaneous tissue (eg, abdomen, upper buttocks)
Lupron®: 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 bone age every 6-12 months, testosterone in males and estradiol in females; Tanner staging
Prostatic cancer: LH and FSH levels, serum testosterone (2-4 weeks after initiation of therapy), PSA; weakness, paresthesias, and urinary tract obstruction in first few weeks of therapy. Screen for diabetes and cardiovascular risk prior to initiating 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
Do not take any new prescriptions, OTC medications, or herbal products during therapy without consulting prescriber. If self-administered, follow exact direction for use and do not discontinue without consulting prescriber. 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 (use caution when driving or engaging in tasks that require alertness until response to drug is known); nausea or vomiting (small frequent meals, frequent mouth care, lozenges, or chewing gum may help); constipation (increased bulk and water in diet or stool softener may help); hot flashes or flushing (cold cloth and cool environment may help); breast swelling or tenderness; or decreased libido or impotence. Report chest pain; palpitations; irregular heart beat; swelling of extremities; weight gain; shortness of breath; difficulty urinating; weakness or numbness in hands, feet, or legs; CNS changes (depression, mood swings, insomnia); continuation of menstruation; pain, swelling, or redness at injection site; or any other persistent adverse reaction.
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. Evaluate results of laboratory tests, therapeutic effectiveness (according to use), and adverse response in first few weeks and periodically thereafter during therapy. Instruct patients with diabetes to monitor glucose levels closely; may impact effectiveness of antidiabetic agents. Teach patient (or caregiver) proper use if self-administered (eg, storage, injection technique, syringe/needle disposal), possible side effects/appropriate interventions, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution, as acetate [depot formulation]:
Eligard®: 7.5 mg [contains polylactide-co-glycolide; released over 1 month]
Eligard®: 22.5 mg [contains polylactide-co-glycolide; released over 3 months]
Eligard®: 30 mg [contains polylactide-co-glycolide; released over 4 months]
Eligard®: 45 mg [contains polylactide-co-glycolide; released over 6 months]
Lupron Depot-Ped®: 7.5 mg, 11.25 mg, 15 mg [contains polylactide-co-glycolide, polysorbate 80; released over 1 month]
Lupron Depot®: 3.75 mg, 7.5 mg [contains polylactide-co-glycolide, polysorbate 80; released over 1 month]
Lupron Depot®-3 Month: 11.25 mg, 22.5 mg [contains polylactide-co-glycolide, polysorbate 80; released over 3 months]
Lupron Depot®-4 Month: 30 mg [contains polylactide-co-glycolide, polysorbate 80; released over 4 months]
Injection, solution, as acetate: 5 mg/mL (2.8 mL)
Lupron®: 5 mg/mL (2.8 mL) [contains benzyl alcohol]
Pricing: U.S. (www.drugstore.com)
Kit (Leuprolide Acetate)
1 mg/0.2 mL (1): $339.98
Kit (Lupron Depot)
3.75 mg (1): $639.96
22.5 mg (1): $2172.25
30 mg (1): $2879.59
Kit (Lupron Depot-Ped)
7.5 mg (1): $730.55
References
Adjei AL and Hsu L, “Leuprolide and Other LH-RH Analogues,” Pharm Biotechnol, 1993, 5:159-99.
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.
Chrisp P and Sorkin EM, “Leuprorelin. A Review of Its Pharmacology and Therapeutic Use in Prostatic Disorders,” Drugs Aging, 1991, 1(6):487-509.
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.
Drago JR, Rohner T, Santen R, et al, "Leuprolide: A Review of its Effects in Animals and Man," Br J Clin Pract Suppl, 1985, 37:4-7, 16-9.
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.
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Breast Cancer,” Version 1.2009. Available at http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf.
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Prostate Carcinoma,” Version 2.2009. Available at http://www.nccn.org/professionals/physician_gls/PDF/prostate.pdf
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, 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.
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 February 2011
Content last modified February 2011
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