No

Antineoplastic Agent, Miscellaneous; Luteinizing Hormone-Releasing Hormone Analog

Palliative treatment of advanced prostate carcinoma (alternative when orchiectomy or estrogen administration are not indicated or are unacceptable to the patient); combination therapy with flutamide for treating metastatic prostatic carcinoma; endometriosis (3.75 mg depot only); central precocious puberty (may be used an agent to treat precocious puberty because of its effect in lowering levels of LH and FSH, testosterone, and estrogen).

X

Hypersensitivity to leuprolide; spinal cord compression (orchiectomy suggested); undiagnosed abnormal vaginal bleeding; women who are or may be pregnant should not receive Lupron® Depot®

Use with caution in patients hypersensitive to benzyl alcohol; after 6 months use of Depot® leuprolide, vertebral bone density decreased (average 13.5%); long-term safety of leuprolide in children has not been established; urinary tract obstruction may occur upon initiation of therapy. Closely observe patients for weakness, paresthesias, and urinary tract obstruction in first few weeks of therapy. Tumor flare and bone pain may occur at initiation of therapy; transient weakness and paresthesia of lower limbs, hematuria, and urinary tract obstruction in first week of therapy; animal studies have shown dose-related benign pituitary hyperplasia and benign pituitary adenomas after 2 years of use.

>10%:

Central nervous system: Depression, pain

Endocrine & metabolic: Hot flashes

Gastrointestinal: Weight gain, nausea, vomiting

1% to 10%:

Cardiovascular: Cardiac arrhythmias, edema

Central nervous system: Dizziness, lethargy, insomnia, headache

Dermatologic: Rash

Endocrine: Estrogenic effects (gynecomastia, breast tenderness)

Gastrointestinal: Nausea, vomiting, diarrhea, GI bleed

Hematologic: Decreased hemoglobin and hematocrit

Neuromuscular & skeletal: Paresthesia, myalgia

Ocular: Blurred vision

<1%: Myocardial infarction, thrombophlebitis, pulmonary embolism

General supportive care

Store unopened vials of injection in refrigerator, vial in use can be kept at room temperature ( less than or equal to 30°C/86°F) for several months with minimal loss of potency. Protect from light and store vial in carton until use. Do not freeze.

Depot® may be stored at room temperature. Upon reconstitution, the suspension is stable for 24 hours; does not contain a preservative.

Continuous daily 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

Onset of action: Serum testosterone levels first increase within 3 days of therapy

Duration: Levels decrease after 2-4 weeks with continued therapy

Metabolism: Destroyed within the GI tract

Bioavailability: Orally not bioavailable; S.C. and I.V. doses are comparable

Half-life: 3-4.25 hours

Elimination: Not well defined

Requires parenteral administration

S.C.: 20-45 mcg/kg/day

I.M. (Depot®) formulation: 0.3 mg/kg/dose given every 28 days

less than or equal to 25 kg: 7.5 mg

>25-37.5 kg: 11.25 mg

>37.5 kg: 15 mg

Adults:

Male: Advanced prostatic carcinoma:

Implant (Viadur®): One subcutaneous implant for 12 months; must be removed after 12 months of hormonal therapy; another implant may be inserted to continue therapy

S.C.: 1 mg/day or

I.M., Depot® (suspension): 7.5 mg/dose given monthly (every 28-33 days)

Female: Endometriosis: I.M., Depot® (suspension): 3.75 mg monthly for up to 6 months

When administering the Depot® form, do not use needles smaller than 22-gauge; reconstitute only with diluent provided

Precocious puberty: GnRH testing (blood LH and FSH levels), testosterone in males and estradiol in females; closely monitor patients with prostatic carcinoma for weakness, paresthesias, and urinary tract obstruction in first few weeks of therapy

Interferes with pituitary gonadotropic and gonadal function tests during and up to 4-8 weeks after therapy

Depression is common; may cause drowsiness, dizziness, or insomnia

None reported

No information available to require special precautions

No effects or complications reported

Use as directed. Do not discontinue abruptly; consult prescriber. 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 or analgesics may help), hot flashes - flushing or redness (cold clothes and cool environment may help). Report irregular or rapid heartbeat, unresolved nausea or vomiting, numbness of extremities, breast swelling or pain, difficulty breathing, or infection at injection sites. Pregnancy/breast-feeding precautions: Do not get pregnant; females must use use barrier contraceptives during and for a time following therapy. Breast-feeding is not recommended.

Patient must be taught aseptic technique and S.C. injection technique. Rotate S.C. injection sites frequently. Disease flare (increased bone pain, urinary retention) can briefly occur with initiation of therapy.

Implant (Viadur®): 65 mg leuprolide

Injection: 5 mg/mL (2.8 mL)

Powder for injection (depot):

Depot®: 3.75 mg, 7.5 mg

Depot-3® Month: 11.25 mg, 22.5 mg

Depot-4® Month: 30 mg

Depot-Ped™: 7.5 mg, 11.25 mg, 15 mg

Adjei AL and Hsu L, "Leuprolide and Other LH-RH Analogues," Pharm Biotechnol, 1993, 5:159-99.

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.

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.

Kavanagh JJ, Roberts W, Townsend P, et al, "Leuprolide Acetate in the Treatment of Refractory or Persistent Epithelial Ovarian Cancer," J Clin Oncol, 1989, 7(1):115-8.

Lee PA and Page JG, "Effects of Leuprolide in the Treatment of Central Precocious Puberty," J Pediatr, 1989, 114(2):321-4.

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.