Leuprolide Acetate

As with other GnRH agonists, patients may experience hot flashes. During the first few weeks of treatment, patients may also experience increased bone pain, increased difficulty in urinating, and the onset or aggravation of weakness or paralysis. Patients should notify their doctor if they develop new or worsened symptoms after beginning ELIGARD®  treatment. Patients should be told about the injection site related adverse reactions, such as transient burning/stinging, pain, bruising, and redness. These injection site reactions are usually mild and reversible. If they do not resolve, patients should tell their doctor. If the patient experiences an allergic reaction, they should contact their doctor immediately.

General

Prostate Cancer

• In patients with stage B2 or C prostate cancer, initiate leuprolide and antiandrogen 8 weeks prior to and continue during radiation therapy.200

• In patients with stage D2 metastatic prostate cancer, initiate leuprolide and antiandrogen therapy concomitantly and continue until disease progression.200

Uterine Leiomyomata

• Lupron Depot: Release characteristics of a fractional dose of the 11.25-mg (3-month) injectable suspension formulation are not equivalent to the same dose of the 3.75-mg (once-monthly) formulation and should not be used for monthly doses.116 191

• Use of the 3-month formulation of leuprolide acetate injectable suspension (Lupron Depot-3 month 11.25 mg) recommended only when 3 months of hormonal suppression is necessary.191

• Prior to initiating leuprolide therapy, consider 1-month trial of iron therapy alone, since some patients may respond adequately to iron alone.116 181 191

Precocious Puberty: Baseline Evaluation Prior to Initiating Therapy

• Measure height and weight.155 156

• Determine serum testosterone or estrogen concentrations in boys or girls, respectively.155 156

• Determine adrenal steroid and β-human chorionic gonadotropin concentrations to rule out congenital adrenal hyperplasia and chorionic gonadotropin secreting tumors, respectively.155 156

• Perform pelvic, adrenal, or testicular ultrasound examination to rule out steroid secreting tumors and cranial CT to rule out intracranial tumors.155 156

Administration

Administer by IM injection100 101 116 155 180 187 190 191 or sub-Q injection.99 156 192 193 194

Leuprolide acetate injection and suspension (Lupron Depot) have comparable efficacy and safety in the treatment of advanced prostate cancer.100 101 In most patients, use of the suspension may be preferred to use of the injection because of greater convenience of administration and patient compliance with therapy.101 121

IM Administration

Administer leuprolide acetate suspension (Lupron Depot) by IM injection once monthly as the 3.75- or 7.5-mg depot 1-month formulation;100 101 116 155 180 187 once every 3 months as the 11.25- or 22.5-mg long-acting 3-month formulation;100 101 116 155 180 187 190 191 once every 4 months as the 30-mg long-acting 4-month formulation,100 101 116 155 180 187 190 or once every 24 weeks as the 45-mg long-acting 6-month formulation.190

Release characteristics of a fractional dose of the 22.5-mg (3-month), 30-mg (4-month), or 45-mg (6-month) suspension formulation (Lupron Depot) are not equivalent to the same dose of the 7.5-mg (once-monthly) formulation and should not be used for monthly doses for treatment of prostate cancer.180 187 190

Release characteristics of a fractional dose of the 11.25-mg (3-month) suspension formulation (Lupron Depot) are not equivalent to the same dose of the 3.75-mg (once-monthly) formulation and should not be used for monthly doses for treatment of endometriosis or uterine leiomyomata.116 191

Administer leuprolide acetate suspension (Lupron Depot-Ped) by IM injection once every 4 weeks as a 3.75-, 7.5-, or 15-mg depot 1-month formulation.155

Rotate injection sites periodically.100 101 116 155 156

Suspension is not intended for self-administration;104 administer under the supervision of a clinician.100 101 104 116 155 180 187 190 191

Reconstitution

Leuprolide acetate powder for injectable suspension (Lupron Depot) is available in a dual-chamber, disposable, single-use syringe;100 116 155 190 191 chamber 1 of the system contains leuprolide acetate lyophilized powder, and chamber 2 contains the sterile diluent supplied by the manufacturer.100 116 155 190 191

Reconstitute dual-chamber, disposable, single-use syringes containing 3.75, 7.5, 11.25, 15, 22.5, 30, or 45 mg of leuprolide acetate extended-release for injectable suspension with the accompanying diluent in accordance with the instructions provided by the manufacturer.100 116 155 190 191

While keeping the syringe upright, gently mix to thoroughly disperse the particles and obtain a uniform milky suspension.100 116 155 190 191

Following reconstitution, immediately inject entire contents of the syringe to provide a 3.75-, 7.5-, 11.25-, 15-, 22.5-, 30-mg, or 45-mg dose, depending on the labeled concentration of the syringe used.100 116 155 190 191

Sub-Q Administration

Administer leuprolide acetate injection by sub-Q injection once daily.99 156 193 194

Administer leuprolide acetate suspension (Eligard) by sub-Q injection once monthly as a 7.5-mg formulation, once every 3 months as a 22.5-mg formulation, once every 4 months as a 30-mg formulation, or once every 6 months as a 45-mg formulation.192

Administer leuprolide acetate suspension (Eligard) in an area with sufficient soft or loose sub-Q tissue (e.g., upper- or mid-abdominal area, upper buttocks).192 Avoid areas with excessive pigment, hair, or brawny or fibrous sub-Q tissue (nodules, lesions) or locations that could be rubbed or compressed (e.g., with a belt or clothing waistband).192

Rotate injection sites periodically.1 99 192 193 194

When substitution of another syringe for the one provided by the manufacturer for use with leuprolide acetate injection is required, a disposable, low-dose, U-100 insulin syringe is the only syringe that should be used.98 104 193

Reconstitution

Leuprolide acetate powder for injectable suspension (Eligard) is available in a single-use kit, containing 2 separate disposable syringes;192 syringe 1 of the system contains leuprolide acetate powder, and syringe 2 contains the polymeric (non-gelatin-containing) delivery system (Atrigel).192

Allow the kit to reach room temperature before reconstituting.192

Reconstitute single-use syringes containing 7.5, 22.5, 30, or 45 mg of leuprolide acetate powder for injectable suspension with the accompanying polymeric delivery system in accordance with the instructions provided by the manufacturer.192

Following reconstitution, administer within 30 minutes.192 Inject the entire contents of the syringe to provide a 7.5-, 22.5-, 30-, or 45-mg dose, depending on the labeled concentration used.192

Dosage

Available as leuprolide acetate; dosage of injection and suspension expressed in terms of the salt.1 100 116 155 156 180 187 190 191 192 193 194

Pediatric Patients

Central Precocious Puberty

Individualize dosage according to actual body weight;155 156 161 younger children (i.e., children weighing <25 kg) generally appear to require higher dosages on a mg/kg basis than older children (i.e., children weighing ≥25 kg).155 156

Confirm inhibition of gonadotropin secretion and suppression of ovarian or testicular steroidogenesis after 1–2 months of initial therapy or when changing dosage by evaluation of GnRH stimulation test, Tanner staging, and sex steroid concentrations.155 156 159

Prior to initiation of therapy, perform baseline evaluations.155 156 (See Baseline Evaluation prior to Initiating Therapy under Dosage and Administration.)

In most children, the first dosage found to adequately inhibit gonadotropin secretion and suppress ovarian or testicular steroidogenesis can be maintained for the duration of therapy.155 156

Data currently are insufficient for specific dosage recommendations in children in whom therapy was initiated at a low dosage and at a very young age and whose weight has changed such that the patient would be in a different weight range/dose category.155 156 The manufacturer recommends that inhibition of gonadotropin secretion and suppression of ovarian or testicular steroidogenesis be monitored closely in children whose weight has increased considerably while receiving therapy.155 156

IM

Leuprolide acetate suspension (Lupron Depot-Ped): Initially, 0.3-mg/kg (minimum 7.5 mg) every 4 weeks in girls <8 years of age or boys <9 years of age.155 158

Initial Dosage for Children (Girls <8 Years of Age or Boys <9 Years of Age)155

Weight	Dosage of leuprolide acetate suspension (Lupron Depot-Ped)
≤25 kg	7.5 mg every 4 weeks
25–37.5 kg	11.25 mg every 4 weeks
>37.5 kg	15 mg every 4 weeks

Titrate dose upward in increments of 3.75 mg every 4 weeks until clinical or laboratory tests indicate no disease progression.155

Therapy usually is continued until fusion of the epiphyses157 or attainment of appropriate chronologic pubertal age (e.g., consideration made at 11 and 12 years of age in girls and boys, respectively).155 156 157

Sub-Q

Leuprolide acetate injection (Lupron for Pediatric Use): Initially 50 mcg/kg once daily for girls <8 years of age or boys <9 years of age.156 158 If total suppression of ovarian or testicular steroidogenesis is not achieved, titrate dosage upward by 10 mcg/kg daily to establish maintenance dosage.156

Adults

Advanced Prostate Cancer Daily Therapy with Leuprolide Acetate Injection Sub-Q

Usually, 1 mg daily.1 99

Dosages up to 20 mg daily have been used by some clinicians; however, dosages >1 mg daily have not resulted in a greater incidence of remission.2 10 22 23 33

For patients at risk of serious adverse affects, consider initiating therapy with daily administration of leuprolide acetate injection for 2 weeks prior to IM administration of leuprolide acetate suspension (Lupron Depot) to permit discontinuance of therapy if warranted.101 180 187 (See Endocrine Effects under Cautions.)

Therapy with Extended-release Suspension IM

7.5 mg once monthly as the monthly formulation (Lupron Depot),100 101 or 22.5 mg every 12 weeks as the 3-month formulation (Lupron Depot 22.5 mg for 3-month administration),180 190 or 30 mg once every 16 weeks as the 4-month formulation (Lupron Depot 30 mg for 4-month administration),187 190 or 45 mg once every 24 weeks as the 6-month formulation (Lupron Depot 45 mg for 6-month administration).190

If a monthly dose is missed, a delay of ≤12 days may or may not compromise the patient’s treatment; however, if a monthly dose is missed by ≥2 weeks, serum testosterone concentrations will increase substantially.101

Sub-Q

Eligard: 7.5 mg once monthly as the monthly formulation, or 22.5 mg once every 3 months as the 3-month formulation, or 30 mg once every 4 months as the 4-month formulation, or 45 mg once every 6 months as the 6-month formulation.192

Endometriosis Initial Treatment IM

3.75 mg once monthly as the monthly formulation (Lupron Depot) for 6 consecutive months116 or 11.25 mg every 3 months as the 3-month formulation (Lupron Depot-3 month 11.25 mg) for a total of 6 months.191 Administer with or without norethindrone acetate (5 mg daily).116 191

Retreatment If Symptoms Recur after Initial Treatment

Retreatment with additional courses of leuprolide alone is not recommended; if retreatment is considered, administer a single 6-month course of leuprolide acetate suspension in conjunction with norethindrone acetate (and elemental calcium 1 g daily).116 191

Assess BMD prior to therapy to ensure that values are within normal limits.116 191 (See Musculoskeletal Effects under Cautions.)

IM

3.75 mg once monthly as the monthly formulation (Lupron Depot) for a total of 6 months or 11.25 mg every 3 months as the 3-month formulation (Lupron Depot-3 month 11.25 mg) for a total of 6 months.116 191 Administer in conjunction with oral norethindrone acetate (5 mg daily).116 191

Additional courses of treatment after a single 6-month retreatment course are not recommended.116 191

Uterine Leiomyomata IM

3.75 mg once monthly as the monthly formulation (Lupron Depot) for up to 3 consecutive months in conjunction with iron therapy.116

11.25 mg of the 3-month formulation (Lupron Depot-3 month 11.25 mg) as a single injection in conjunction with iron therapy.191 Use of the 3-month formulation recommended only when 3 months of hormonal suppression is necessary.191

If additional therapy is considered, assess BMD prior to therapy to ensure that values are within normal limits.116 191 (See Musculoskeletal Effects under Cautions.)

Prescribing Limits

Adults

Endometriosis Initial Treatment IM

Limit initial course of therapy to 6 months.116 191

Retreatment If Symptoms Recur after Initial Treatment IM

Limit retreatment of symptom recurrence to 6 months; retreatment with leuprolide alone is not recommended.116 191

Additional courses of treatment after a single 6-month retreatment course are not recommended.116 191

Uterine Leiomyomata IM

Lupron Depot 3.75 mg monthly formulation: Maximum 3 consecutive months of therapy recommended.116

Lupron Depot 11.25 mg (3-month formulation): A single injection of 11.25 mg recommended.191

Safety and efficacy of >6 months of therapy not evaluated.191