leuprolide (Lupron, Lupron Depot, Lupron Depot 3 Month, Lupron Depot 4 Month, Lupron Depot 6 Month, Lupron Depot-Ped, Eligard)

Dosing and uses of Lupron, Lupron Depot (leuprolide)

• Adult
• Pediatric

 

Adult dosage forms and strengths

Eligard

• 7.5mg (monthly)
• 22.5mg (3 months)
• 30mg (4 months)
• 45mg (6 months)

Lupron Depot

• 3.75mg (monthly)
• 7.5mg (monthly)
• 11.25mg (3 months)
• 22.5mg (3 months)
• 30mg (4 months)
• 45mg (6 months)

Leuprolide acetate

• 5mg/mL

 

Advanced Prostate Cancer

Lupron: 7.5 mg IM monthly, 22.5 mg IM every 3 months, 30 mg IM every 4 months, or 45 mg IM every 6 months 

Eligard: 7.5 mg SC monthly, 22.5 mg SC every 3 months, 30 mg SC every 4 months, 45 mg SC every 6 months

Leuprolide acetate: 1 mg/0.2 mL/day SC

Monitoring

• Measure prostate-specific antigen (PSA) in first few weeks of therapy; measure luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels and serum testosterone after 4 weeks of therapy

 

Endometriosis

3.75 mg IM monthly for up to 6 months or 11.25 mg IM every 3 months for 2 doses (6 months total) 

Recommended duration of treatment is 6 months; may treat again for additional 6 months, but with concomitant administration of norethindrone 

 

Uterine Leiomyomata (Fibroids)

3.75 mg IM monthly for up to 3 months or 11.25 mg IM once 

Use concomitant iron treatment

 

Breast Cancer in Premenopausal Ovarian Ablation (Off-label)

3.75 mg IM every 28 days or 11.25 mg IM every 3 months for up to 24 months

 

Administration

Evaluate cardiovascular risk before initiating therapy and routinely thereafter

Routinely check for diabetes (blood glucose and Hb A1C) before initiating therapy and during treatment

Rotate SC injection sites frequently

In men, recommend calcium, vitamin D, exercise to prevent osteoporosis

Monitor serum PSA, testosterone, prostatic acid phosphatase (PAP)

 

Pediatric dosage forms and strengths

Lupron Depot-Ped

• 7.5mg (monthly)
• 11.25mg (monthly)
• 15mg (monthly)
• 11.25mg (3 months)
• 30mg (3 months)

Leuprolide acetate

• 5mg/mL

 

Central Precocious Puberty

Indicated when signs of sexual maturity begin to develop in girls <8 years old and boys <9 years old; may be discontinued at appropriate age of onset of puberty (eg, 11 years in females and 12 years in males), at physician's discretion

<2 years old: Safety and efficacy not established

Lupron Depot-Ped (monthly dose)

• <25 kg: 7.5 mg IM monthly
• >25 kg to 37.5 kg: 11.25 mg IM monthly
• >37.5 kg: 15 mg IM monthly
• Assess response 1-2 months after initial injection; if adequate hormonal and clinical suppression not achieved with starting doses, increase next monthly dose to the next higher level

Lupron Depot-Ped (3-month dose)

• 11.25 mg or 30 mg as single IM injection every 3 months (dose not based on weight)
• Regardless of dose chosen, goals are to suppress pituitary gonadotropins and peripheral sex steroids and to arrest progression of secondary sexual characteristics
• Assess response 2-3 months after initial injection and 6 months after injection

Leuprolide acetate

• 50 mcg/kg/day SC; may be titrated upward by 10 mcg/kg/day if downregulation not achieved

 

Administration

Do not use partial syringes or combination of syringes to achieve particular dose

Vary injection site periodically

Monitor response with gonadotropin-releasing hormone (GnRH) stimulation test; measure testosterone in males and estradiol in females, Tanner staging

Check height and bone age every 6-12 months while using Lupron Depot-Ped

Measure bone mineral density 

 

Lupron, Lupron Depot (leuprolide) adverse (side) effects

>10%

Hot flashes (57%)

Cardiovascular changes or ischemia (19%)

Fatigue (18%)

Pain (13%)

Peripheral edema (12%)

 

1-10%

Asthenia (10%)

Gynocomastia (7%)

Headache (7%)

Testicular atrophy (7%)

Anorexia (6%)

Anemia (5%)

Bone pain (5%)

Constipation (7%)

Urinary frequency (6%)

Dermatitis (5%)

Dizziness (5%)

Nausea and vomiting (5%)

Gastroenteritis (3%)

Myalgia (3%)

UTI (3%)

Dyspnea (2%)

 

Frequency not defined

Convulsion

Depression

Neuropathy

Decreased bone density

Hematuria

Obstruction of ureter or bladder

Impotence

Sweating

Implant site reactions (pain, bruising, edema)

Spinal cord compression (rare)

 

Postmarketing Reports

Anaphylactoid or asthmatic reaction

Rash, urticaria, photosensitivity reactions

Localized reactions (eg, induration, abscess)

Mood swings, including depression; rare reports of suicidal ideation and attempts (many, but not all, of these patients had history of depression)

Fibromyalgia (eg, joint and muscle pain, headaches, sleep disorder, GI distress, shortness of breath)

Reduced WBC count

Hepatobiliary: Serious liver injury (rare)

Injury/poisoning/procedural complications: Spinal fracture

Musculoskeletal/connective tissue: Tenosynovitislike symptoms

Neurologic: Convulsion, peripheral neuropathy, paralysis

Cardiovascular: Hypotension

Pituitary apoplexy: Symptoms include sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, cardiovascular collapse; immediate medical attention required

 

Warnings

Contraindications

Hypersensitivity to GnRH or GnRH-agonist analogues

Undiagnosed vaginal bleeding

Pregnancy

Eligard not to be used in children

Breastfeeding

 

Cautions

Urinary tract obstruction, vertebral metastases, or psychiatric disorder may occur

May cause development or worsening of depression

Females treated for precocious puberty may experience abnormal menses; inform healthcare provider if bleeding continues

Decrease in bone density reported when drug used for >6 months

Worsening of endometriosis or uterine leiomyomata symptoms with therapy reported initially

Worsening of glycemic control reported in men receiving GnRH agonists; monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes

Prostate cancer symptoms may worsen during initial treatment period

Convulsions reported

Androgen deprivation therapy may prolong the QT/QTc interval; consider whether benefits of androgen deprivation outweighs potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and patients taking drugs known to prolong the QT interval; correct electrolyte abnormalities and monitor ECG and electrolytes periodically

Men receiving GnRH agonists for prostate cancer have slightly increased risk of diabetes, heart attack, stroke, and sudden death

In women, duration of treatment with GnRH agonists not to exceed 1 year, except in treatment of breast cancer

Transient increase in serum levels of testosterone during treatment may result in worsening of symptoms or onset of new signs and symptoms during first few weeks of treatment, including bone pain, neuropathy, hematuria, bladder outlet obstruction, ureteralobstruction, or spinal cord compression; monitor patients at risk closely and manage as appropriate

 

Pregnancy and lactation

Pregnancy category: X

Lactation: Contraindicated; not known if drug is excreted in breast milk; make decision to either discontinue nursing or discontinue drug, taking into account risk and benefits to the mother

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Lupron, Lupron Depot (leuprolide)

Mechanism of action

Agonist analogue of luteinizing hormone-releasing hormone (LHRH)

When administered continuously, decreases LH and FSH levels by acting as potent inhibitor of gonadotropin secretion; decrease in LH and FSH levels followed by suppression of ovarian and testicular steroidogenesis; testosterone levels reduced to below castrated levels in males

 

Absorption

Bioavailability: SC, 80-94%

 

Distribution

Protein bound: 43-49%

Vd: Males, 27 L

 

Metabolism

Metabolized to smaller inactive peptides, a pentapeptide (metabolite I), tripeptides (metabolites II and III), and a dipeptide (metabolite IV); these fragments may be further catabolized

 

Elimination

Half-life: 3 hr

Clearance: 8.34 L/hr

Excretion: Urine (<5% as parent and major pentapeptide metabolite)