leuprolide

(effect on hormone levels)

ROUTE	ONSET†	PEAKdhara	DURATIONi
SUBQ	within 1st wk	2–4 wk	4–12 wk
IM	within 1st wk	2–4 wk	4–12 wk
IM-depot	within 1st wk	2–4 wk	4–12 wk

†Initial transient ↑ in testosterone and estradiol levels.

†Maximum decline in testosterone and estradiol levels.

iRestoration of normal pituitary-gonadal function; in amenorrheic patients, normal menses usually returns 60–90 days after treatment is discontinued.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to GnRH agonists
OB: Pregnancy
Lactation: Lactation.

Use Cautiously in:

Hypersensitivity to benzyl alcohol (results in induration and erythema at SUBQ site)
Congenital long QT syndrome, HF, electrolyte abnormalities, or concurrent use of other drugs known to prolong the QT interval
Seizures, cerebrovascular disorders, CNS tumor, or concurrent use of bupropion or SSRIs
Women of reproductive potential
Pedi: Children <1 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: angina, arrhythmias, MI.
Depot: QT interval prolongation, vasodilation.

Derm: Depot: hair growth, rash, ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS (AGEP), DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN).
SUBQ: dry skin, hair loss, pigmentation, skin cancer, skin lesions.

EENT: blurred vision.
Depot: epistaxis, throat nodules.
SUBQ: hearing disorder.

Endo: breast swelling, breast tenderness, hot flushes, hyperglycemia.

F and E: hypercalcemia, lower extremity edema.

GI: anorexia, diarrhea, dysphagia, nausea, vomiting.
Depot: gingivitis, HEPATOTOXICITY, nonalcoholic fatty liver disease.
SUBQ: GI BLEEDING, hepatic impairment, peptic ulcer, rectal polyps.

GU: ↓fertility (males), ↓ libido, ↓ testicular size, dysuria, incontinence, testicular pain.
Depot: cervix disorder.
SUBQ: bladder spasm, penile swelling, prostate pain, urinary obstruction.

Local: burning, itching, swelling at injection site.

Metab: Depot: ↓bone density, hyperlipidemia, hyperuricemia.

MS: fibromyalgia, transient ↑ in bone pain (prostate cancer only).
SUBQ: ankylosing spondylitis, joint pain, pelvic fibrosis, temporal bone pain.

Neuro: SUBQ: aggression, anger, anxiety, dizziness, dysgeusia, headache, impatience, intracranial hypertension (children), irritability, lethargy, memory disorder, mood swings, peripheral neuropathy, SEIZURES, STROKE, syncope.
Depot: depression, drowsiness, intracranial hypertension (children), personality disorder.

Resp: hemoptysis, PULMONARY EMBOLISM.
SUBQ: cough, pleural rub, pulmonary fibrosis, pulmonary infiltrate.
Misc: chills, fever, tumor flare.
Depot: body odor.

Interactions ⬆ ⬇

Drug-Drug:

↑antineoplastic effects with antiandrogens (megestrol, flutamide).
Bupropion or SSRIs may ↑ risk of seizures.
QT interval prolonging drugs may ↑ risk of QT interval prolongation.

Route/Dosage ⬆ ⬇

Advanced Prostate Cancer

SC (Adults): Leuprolide acetate: 1 mg/day; Eligard: 7.5 mg once monthly, 22.5 mg every 3 mo, 30 mg every 4 mo, or 45 mg every 6 mo. Camcevi: 42 mg every 6 mo.
IM (Adults): Lupron Depot: 7.5 mg once monthly or 22.5 mg every 3 mo or 30 mg every 4 mo or 45 mg every 6 mo.

Endometriosis

IM (Adults): Lupron Depot: 3.75 mg once monthly for up to 6 mo or 11.25 mg every 3 mo for up to 2 doses; if symptoms recur after initial course of therapy, may administer a 2nd course of therapy.

Uterine Fibroids

IM (Adults): Lupron Depot: 3.75 mg once monthly for up to 3 mo or 11.25 mg single injection.

Central Precocious Puberty

SC (Children 2 yr): Leuprolide acetate: 50 mcg/kg/day, may ↑ by 10 mcg/kg/day as required. Fensolvi: 45 mg every 6 mo.
IM (Children 1 yr and >37.5 kg): Lupron Depot-Ped (monthly formulation): 15 mg every 4 wk; may ↑ by 3.75 mg every 4 wk as required.
IM (Children 1 yr and 26–37.5 kg): Lupron Depot-Ped (monthly formulation): 11.25 mg every 4 wk; may ↑ by 3.75 mg every 4 wk as required.
IM (Children 1 yr and 25 kg): Lupron Depot-Ped (monthly formulation): 7.5 mg every 4 wk; may ↑ by 3.75 mg every 4 wk as required.
IM (Children 1 yr): Lupron Depot-Ped (3-month formulation)11.25 or 30 mg every 3 mo.
IM (Children 1 yr): Lupron Depot-Ped (6-month formulation)45 mg every 6 mo.

Availability ⬆ ⬇

(Generic available)

Emulsion for injection (Camcevi) (prefilled syringe): 42 mg;
Lyophilized microspheres for depot injection (Lupron Depot): 3.75 mg; 7.5 mg; 11.25 mg; 22.5 mg; 30 mg; 45 mg;
Lyophilized microspheres for depot injection (Lupron Depot-Ped): 7.5 mg; 11.25 mg; 15 mg; 30 mg; 45 mg;
Lyophilized powder for injection (Fensolvi): 45 mg/vial;
Polymeric matrix injectable formulation for injection (Eligard): 7.5 mg; 22.5 mg; 30 mg; 45 mg;
Solution for injection (leuprolide acetate): 1 mg/0.2 mL;

Assessment ⬆ ⬇

Monitor ECG periodically in patients at risk for QT interval prolongation. Assess patient for palpitations, change in heartbeat, dizziness, short of breath, and fainting.
Assess skin for AGEP (small red-white or red elevations with pus). Assess for DRESS (rash with fever, lymphadenopathy, hepatitis, hematologic abnormalities). Assess for TEN (red, painful raw skin near eyes, mouth/throat, and gentials/urethra/anus). Assess for SJS (flu-like symptoms, rash with blisters).
Prostate Cancer: Assess for an ↑ in bone pain, especially during the first few wk of therapy. Monitor patients with vertebral metastases for ↑ back pain and ↓ sensory/motor function.
- Monitor intake and output ratios; assess for bladder distention in patients with urinary tract obstruction during initiation of therapy.
Fibroids: Assess for severity of symptoms (bloating, pelvic pain, pressure, excessive vaginal bleeding) periodically during therapy.
Endometriosis: Assess for endometrial pain prior to and periodically during therapy.
Central Precocious Puberty: Prior to therapy, confirm diagnosis of central precocious puberty by onset of secondary sex characteristics in girls <8 yr or boys <9 yr. A complete physical and endocrinologic examination, including height, weight, and hand and wrist x-ray; total sex steroid level (estradiol or testosterone); adrenal steroid level; beta human chorionic gonadotropin level; GnRH stimulation test; and computerized tomography of the head must be performed. These parameters are monitored after 1–2 mo and every 3–6 mo during therapy.
- Assess for signs of precocious puberty (menses, breast development, testicular growth) periodically during therapy. Dose is ↑ until no progression of the disease is noted either clinically or by lab test parameters, then usually maintained throughout therapy. Discontinuation of therapy should be considered before age 11 in girls and age 12 in boys.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.Initially ↑, then ↓ luteinizing hormone and follicle-stimulating hormone. This leads to castration levels of testosterone in boys 2–4 wk after initial ↑ in concentrations.
- Monitor testosterone, prostatic acid phosphate, and prostate-specific antigen levels to evaluate response to therapy. Transient ↑ in levels may occur during the 1st mo of therapy for prostate cancer.
- Monitor electrolytes before starting and periodically during therapy. May cause ↑ BUN, serum calcium, uric acid, hypoproteinemia, LDH, alkaline phosphatase, AST, hyperglycemia, hyperlipidemia, hyperphosphatemia, WBC, PT, or aPTT. May also cause ↓ platelets and serum potassium.
- Monitor blood sugar and A1c periodically during therapy.

Implementation ⬆ ⬇

Do not confuse Lupron Depot with Lupron Depot-Ped.
- Norethindrone acetate 5 mg daily may be used to prevent bone density loss from leuprolide.
- Correct electrolyte abnormalities before starting therapy.
SC
- Camcevi: Must be administered by a health care professional. Allow prefilled syringe to stand at room temperature for 30 min before injection. Wear gloves during preparation and administration. Inject into upper- or mid-abdominal area with sufficient soft or loose SUBQ tissue that has not recently been used. Clean the injection site with an alcohol swab. Do NOT inject in areas with brawny or fibrous SUBQ tissue or locations that can be rubbed or compressed (with a belt or clothing waistband). Avoid applying heat directly to the site of injection. Pinch skin and inject at 90° angle; release skin and inject full contents of syringe.
- Eligard SUBQ formulation: Bring to room temperature before mixing. Reconstitution: Assemble the Eligard kit and reconstitute solution using syringes provided, as directed by manufacturer. Wearing gloves, mix in syringes as directed by manufacturer; do not shake. Solution must reach room temperature before administration and must be administered within 30 min of mixing or discarded. Solution is light tan to tan in color. Inject into abdomen, upper buttocks, or anywhere that has adequate amounts of SUBQ tissue without excessive pigment, nodules, lesions, or hair. Vary site with each injection. Store in refrigerator; may also be stored at room temperature in original packing for up to 8 wk before mixing.
- Fensolvi: Must be administered by a health care professional. Allow to reach room temperature before reconstitution. Reconstitution: Follow manufacturer's instructions for assembling syringes and mixing.45 mg/0.375 mL. Administer within 30 min or discard. Inject into abdomen or upper buttocks. Avoid areas that have excessive pigment, nodules, lesions, or hair. Pinch skin and inject at 90° angle. Release skin and inject slowly. Rotate injection sites.
IM: Use syringe supplied by manufacturer. Rotate sites.
- Leuprolide depot is only for IM injection.
- Lupron Depot formulationand Lupron Depot-Ped must be administered by a health care professional. Reconstitution: To prepare for injection, screw white plunger into end stopper until stopper begins to turn. Hold syringe upright; release diluent by slowly pushing, over 6–8 sec, until the first stopper is at the blue line in the middle of the barrel. Keep syringe upright. Mix microspheres by shaking syringe until power forms a unified suspension. Tap syringe if caking or clumping occurs. Do not combine syringes or partial syringes to arrive at a dose of Lupron Depot-Ped. Suspension will appear milky. Do not use if powder does not go into suspension. Keep syringe upright; remove cap and expel air. Inject at 90° angle in gluteal area, anterior thigh, or deltoid; aspirate and discard if blood in syringe. Suspension settles very quickly; mix and administer immediately. Administer within 2 hr or discard. Rotate injection sites.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of leuprolide to patient.
Advise patient to readPatient Information before starting therapy.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patient that medication may cause hot flushes. Notify health care professional if these become bothersome.
Leuprolide depot usually causes a temporary discontinuation of menstruation. Advise patient to notify health care professional if menstruation persists or if intermittent bleeding occurs.
Inform patient of the possibility of the development or worsening of depression and occurrence of memory disorders.
May cause fetal harm. Advise females of reproductive potential to use effective contraception during therapy. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise patient that leuprolide may impair fertility.
Prostate Cancer: Instruct patient and family on SUBQ injection technique. Review patient insert provided with leuprolide patient administration kit.
- Instruct patient to take medication exactly as directed. Take missed doses as soon as remembered unless not remembered until next day.
- Inform patient that bone pain may ↑ at initiation of therapy, but will resolve with time. Advise patient to discuss use of analgesics to control pain with health care professional.
- Instruct patient to notify health care professional promptly if difficulty urinating, weakness, or numbness occurs.
Endometriosis: Advise patient to use a form of contraception other than oral contraceptives during therapy. Inform patient that amenorrhea is expected but does not guarantee contraception. Advise patient that breastfeeding should be avoided during therapy.
Central Precocious Puberty: Instruct patient and family on the proper technique for SUBQ injection. Emphasize the importance of administering the medication at the same time each day. Rotate injection sites periodically.
- Inform patient and parents that if injections are not given daily, pubertal process may be reactivated.
- Advise patient and parents that during the first 2 mo of therapy, patient may experience a light menstrual flow or spotting. Health care professional should be notified if this continues beyond 2nd mo.
- Instruct patient and parents to notify health care professional immediately if irritation at the injection site or unusual signs or symptoms occur.

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇