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Leuprolide Acetate

Pronunciation

Pronunciation: loo-PRO-lide ASS-uh-TATE
Class: Gonadotropin-releasing hormone analog

Trade Names

Eligard
- Injection 22.5 (3-month depot)
- Injection 30 mg (4-month depot)
- Injection 45 mg (6-month depot)
- Powder for injection, lyophilized 7.5 mg

Leuprolide Acetate
- Injection 5 mg/mL

Lupron Depot
- Microspheres for injection, lyophilized 3.75 mg
- Microspheres for injection, lyophilized 7.5 mg/mL

Lupron Depot-3 Month
- Microspheres for injection, lyophilized 11.25 mg
- Microspheres for injection, lyophilized 22.5 mg

Lupron Depot-4 Month
- Microspheres for injection, lyophilized 30 mg

Lupron Depot-Ped
- Microspheres for injection, lyophilized 7.5 mg
- Microspheres for injection, lyophilized 11.25 mg
- Microspheres for injection, lyophilized 15 mg

Lupron for Pediatric Use
- Injection 5 mg/mL

Lupron Depot 3.75 mg/11.25 mg (Canada)
Lupron/Lupron Depot 3.75 mg/7.5 mg (Canada)
Lupron/Lupron Depot 7.5 mg/22.5 mg/30 mg (Canada)

Pharmacology

A synthetic luteinizing hormone-releasing hormone (LHRH) agonist that acts as a potent inhibitor of gonadotropin secretion when given continuously and in therapeutic doses. After initial stimulation, chronic administration results in suppression of ovarian and testicular steroidogenesis.

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Pharmacokinetics

Absorption

Not active orally.

Injection Daily

Bioavailability subcutaneous is comparable with IV.

Monthly

C max is 4.6 to 25.3 ng/mL. T max is 4 to 5 h.

Every 3 mo

C max is 36.3 to 127 ng/mL. T max is 4 to 5 h.

Every 4 mo

C max is 59.3 to 150 ng/mL. T max is 3.3 to 4 h.

Every 6 mo

C max is 82 to 102 ng/mL. T max is 4.5 h.

Distribution

Protein binding is 43% to 49%. Mean Vd ss is 27 L.

Metabolism

Inactive metabolites are pentapeptide (metabolite Ι), tripeptides (metabolite ΙΙ and ΙΙΙ), and dipeptide (metabolite ΙV).

Elimination

Plasma half-life is 3 h.

Special Populations

Renal Function Impairment

Pharmacokinetics have not been determined.

Hepatic Function Impairment

Pharmacokinetics have not been determined.

Elderly

Majority of patients studied were 65 y and older.

Indications and Usage

Palliative treatment of advanced prostatic cancer; management of endometriosis in women older than 18 y (depot preparation); treatment of children with central precocious puberty (CPP [pediatric injection or depot pediatric]); uterine leiomyomata (depot preparation).

Contraindications

Pregnancy; lactation; hypersensitivity to GnRH, GnRH agonist analogs, or product components; undiagnosed vaginal bleeding. Eligard is contraindicated in children.

Dosage and Administration

Advanced Prostate Cancer
Adults

Injection; subcutaneous 1 mg/day. Depot; subcutaneous ( Eligard only) 7.5 mg/mo, 22.5 mg every 3 mo, 30 mg every 4 mo, or 45 mg every 6 mo. IM ( Lupron only) 7.5 mg/mo, 22.5 mg every 3 mo, 30 mg every 4 mo.

CPP
Children

Injection; subcutaneous Starting dose: 50 mcg/kg/day as single injection. If total downregulation not achieved, titrate upward by 10 mcg/kg/day, which will be considered the maintenance dose. Depot; IM Starting dose: 25 kg or less, 7.5 mg every 4 wk; 26 to 37.5 kg, 11.25 mg every 4 wk; greater than 37.5 kg, 15 mg every 4 wk. If total downregulation not achieved, titrate upward in 3.75 mg increments every 4 wk, which will be considered the maintenance dose.

Endometriosis
Adults

IM 3.75 mg as single monthly injection or 11.25 mg every 3 mo (depot preparation).

Uterine Leiomyomata
Adults

IM 3.75 mg/mo or one 11.25 mg injection with concomitant iron therapy. Recommended duration of therapy is 3 mo or less.

General Advice

Depot
  • Because of different release characteristics, a fractional dose of the 3-, 4-, or 6-mo depot formulations is not equivalent to the same dose of the monthly formulation and should not be given.
  • Prefilled dual-chamber syringe and single-use kit with 2-syringe mixing system
  • Allow Eligard to reach room temperature before using.
  • Prepare injection following manufacturer's instructions. If microspheres (particles) adhere to the stopper, tap the syringe against finger; remove needle guard and advance plunger to expel air from the syringe. Inject entire contents of syringe IM ( Lupron ) or subcutaneous ( Eligard ). Mix and administer immediately because suspension settles very quickly; reshake suspension if settling occurs.
Injection
  • Prepare injection following manufacturer's instructions.
  • Use syringes included in the kit or low-dose insulin syringes.
  • Do not administer if solution is cloudy, discolored, or contains particulate matter.
  • Rotate injection sites.

Storage/Stability

Store injection below 77°F. Protect from freezing and light; store vial in carton until use.

Store Lupron Depot at controlled room temperature (59° to 86°F). Does not contain a preservative; discard if not used immediately after reconstitution.

Refrigerate Eligard between 35.6° and 46.4°F. Administer within 30 min of mixing.

Drug Interactions

None well documented.

Laboratory Test Interactions

Diagnostic tests of pituitary gonadotropic and gonadal functions during treatment and up to 12 wk after discontinuing depot preparation may be misleading.

Adverse Reactions

Cardiovascular

Vasodilation (68%); ECG changes/ischemia, heart failure, hypertension, murmur, phlebitis/thrombosis (at least 5%); angina, arrhythmia, atrial fibrillation, bradycardia, deep thrombophlebitis, hypotension, MI, tachycardia, varicose vein (less than 5%); syncope (less than 2%); pulmonary embolism (postmarketing).

CNS

Headache/Migraine (65%); depression, insomnia/sleep disorders (31%); asthenia (18%); dizziness/vertigo (16%); decreased libido (11%); neuromuscular disorders (10%); nervousness, paresthesia (8%); anxiety, memory disorder/amnesia (6%); abnormal thinking, confusion, convulsion, delusions, dementia, fatigue, hypesthesia, lethargy, malaise, mood swings, numbness, paralysis, peripheral nephropathy, personality disorder, syncope or blackouts (less than 5%); emotional lability, personality disorder, somnolence (less than 2%); paralysis, spinal fracture (postmarketing).

Dermatologic

Hot flashes/sweats (98%); skin reaction (12%); acne/seborrhea (10%); dermatitis (at least 5%); carcinoma of the skin or ear, clamminess, dry skin, ecchymosis, hair loss, herpes zoster, itching, local skin reactions, nail disorders, night sweats, pigmentation/melanosis, skin lesions (less than 5%); rash including erythema multiforme (2%); hirsutism, skin striae (less than 2%); hair growth, photosensitivity, rash, urticaria (postmarketing).

EENT

Abnormal vision, amblyopia, blurred vision, carcinoma of the ear, conjunctivitis, dry eyes, epistaxis, pharyngitis, tinnitus (less than 5%).

GI

Nausea, vomiting (25%); GI disorder (16%); altered bowel function (14%); anorexia, constipation (at least 5%); colitis, diarrhea, duodenal ulcer, dysphagia, enlarged abdomen, eructation, GI bleeding, gastroenteritis, gingivitis, gum hemorrhage, hepatomegaly, hernia, increased appetite, increased sputum, intestinal obstruction, peptic ulcer, periodontal abscess, rectal polyps, taste disorders, thirst or dry mouth (less than 5%); abdominal pain, dysphagia, gingivitis (less than 2%).

Genitourinary

Vaginitis (28%); testicular atrophy (20%); urinary disorders (17%); breast enlargement, gynecomastia (7%); breast pain or tenderness, impotence (at least 5%); urinary retention, urinary frequency (5%); vaginal bleeding or discharge (2%); balanitis, bladder carcinoma, bladder spasms, dysuria, epididymitis, incontinence, lactation, menstrual disorders, nocturia, penis disorders, testicular pain, testis disorders, UTI (less than 5%); cervix disorder, prostate disorder (less than 2%); prostate pain (postmarketing).

Hematologic-Lymphatic

Anemia (at least 5%); leukopenia, lymphedema, lymphadenopathy (less than 5%).

Lab Tests

Increased triglycerides (12%); increased total cholesterol (7%); abnormal LFTs, decreased albumin, decreased bicarbonate, decreased and increased platelets, decreased and increased prostatic acid phosphatase, decreased and increased urine specific gravity, decreased HDL, decreased Hgb/Hct/RBC, decreased potassium, decreased total protein, eosinophilia, hyperglycemia, hyperlipidemia, hyperphosphatemia, hyperuricemia, increased BUN, increased calcium, increased creatinine, increased PT, increased PTT, increased WBC, thrombocytopenia, uricaciduria (at least 5%).

Local

Injection-site reaction (38%); abscess at injection site (5%).

Metabolic-Nutritional

Edema (21%); weight gain or loss (13%); dehydration (8%); peripheral edema (at least 5%); abnormal healing, diabetes, hypoglycemia, hypoxia, thyroid enlargement (less than 5%).

Musculoskeletal

Joint disorder (16%); myalgia (8%); bone pain (at least 5%); joint pain, leg cramps, neck pain (less than 5%); extremity pain (3%); arthritis (less than 2%); decreased bone density, fibromyalgia, tenosynovitis-like symptoms (postmarketing).

Respiratory

Respiratory disorders (11%); dyspnea, sinus congestion (at least 5%); asthma, bronchitis, cough, emphysema, epistaxis, hemoptysis, lung edema, pharyngitis, pleural effusion, pleural rub, pneumonia, pulmonary fibrosis, rhinitis (less than 5%).

Miscellaneous

Pain (33%); fatigue or malaise (21%); edema (14%); flu syndrome (12%); allergic reaction, androgen-like effects, cellulitis, chills, cyst, enlarged abdomen, enlarged thyroid, fever, infection or inflammation, hiccup, lung disorder, neoplasm, sinusitis, temporal bone swelling, voice alteration, weakness (less than 5%); accelerated muscle maturity, body odor, dry mucous membranes, rigors (less than 2%); anaphylactoid reactions, asthma, pituitary apoplexy (postmarketing).

Precautions

Monitor

Closely observe prostatic cancer patients with metastatic vertebral lesions or with urinary tract obstruction during first few wk of therapy. Monitor therapeutic response by measuring testosterone serum levels, prostate-specific antigen (PSA), and prostatic acid phosphatase. After 1 to 2 mo of initiating CPP therapy or changing doses, monitor GnRH stimulation test, sex steroids, and Tanner staging to confirm downregulation. Verify downregulation in patients whose weight has increased significantly while on therapy. Monitor measurements of bone age for advancement every 6 to 12 mo.


Pregnancy

Category X . Exclude pregnancy before initiating therapy in women of childbearing potential; use nonhormonal method of contraception during treatment.

Lactation

Undetermined.

Children

The safety and efficacy of leuprolide, apart from the pediatric formulations for treatment of CPP, have not been established.

Hypersensitivity

Injection contains benzyl alcohol, which can cause local hypersensitivity reactions. Depot preparation is preservative-free.

Bone density changes

Use of depot preparation may result in decreased bone density. Decreased bone mineral content risk factors may cause additional bone loss with long-term use.

Duration of therapy

Consider discontinuation of CPP therapy before 11 y of age in women and before 12 y of age in men.

Ureteral obstruction/spinal cord compression

Has occurred in prostatic cancer patients treated with LHRH agonists.

Worsening of symptoms

Increase in clinical signs and symptoms of CPP, prostatic cancer, endometriosis, and uterine leiomyomata may occur during early phase of therapy because of transient increases in gonadotropins and sex steroids.

Overdosage

Symptoms

None noted.

Patient Information

  • Review dosing schedule with patient.
  • Advise patient to review information pamphlet that comes with product before starting therapy and periodically thereafter during prolonged treatment.
  • Advise patient that leuprolide depot will be prepared and administered by health care professionals in a medical setting.
  • Advise patient, family, or caregiver of patient receiving leuprolide injection that the medication will usually be prepared and administered by health care professionals in a medical setting, but that home administration is possible if health care provider believes that it is appropriate and safe.
  • If patient will be administering at home, teach patient how to store, prepare, and administer the dose, and dispose of used equipment and supplies. Advise patient to review the patient information leaflet before starting therapy and to read and check for new information each time the medication is refilled.
  • Instruct patient being treated for prostatic cancer to immediately report difficulty urinating, leg weakness, or abnormal sensations in legs.
  • Advise patient that symptoms of the condition may temporarily worsen during the first few wk of treatment and to notify health care provider if symptoms become intolerable or persist for more than a few wk, or if unusual signs or symptoms develop.
  • Advise patients that injection-site reactions (eg, burning, itching, swelling) can occur, but that these are usually mild and go away. Instruct patients to notify their health care provider if injection-site reactions are bothersome or do not go away.
  • Instruct women of childbearing potential to use effective nonhormonal method of contraception.

Copyright © 2009 Wolters Kluwer Health.

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