Leuprolide

Leuprolide is a prescription medication used for the treatment of advanced prostate cancer, endometriosis, fibroids, and central precocious puberty.

• Leuprolide is available under the following different brand names: Lupron, Lupron Depot, Lupron Depot 3 Month, Lupron Depot 4 Month, Lupron Depot 6 Month, Lupron Depot-Ped, Eligard, Fensolvi, Camcevi

Adult dosage

Injection, powder for reconstitution (Eligard)

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

Injection, powder for reconstitution (Fensolvi)

• 45mg/syringe in kit

Injection, suspension (Lupron Depot)

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

Injection, emulsion (Camcevi)

• 42mg/prefilled syringe (6 months)

Injection, solution (generic leuprolide acetate)

• 5mg/mL vial (daily) 

Pediatric dosage

Injection, lyophilized powder for reconstitution

Reconstitution results in suspension for IM injection 

Monthly

• 7.5 mg (Lupron Depot-Ped)
• 11.25 mg (Lupron Depot-Ped)
• 15 mg (Lupron Depot-Ped)
• 3-month
• 11.25 mg (Lupron Depot-Ped)
• 30 mg (Lupron Depot-Ped)

Kit, injectable suspension

• Reconstitution results in suspension for IM injection

Kit contains 2 syringes (Fensolvi)

• Syringe AS contains diluent for reconstitution
• Syringe B contains 45 mg lyophilized leuprolide acetate powder

Injectable solution

• 5mg/mL (generic)

Advanced Prostate Cancer

Adult dosage

• 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
• Camcevi: 42 mg SC every 6 months

Endometriosis

Adult dosage

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

Uterine Leiomyomata (Fibroids)

Adult dosage

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

Central Precocious Puberty

Pediatric dosage

• Children less than 2 years old: Safety and efficacy not established

Lupron Depot-Ped (monthly dose)

• Children weighing less than 25 kg: 7.5 mg IM monthly
• Children weighing above 25 kg to 37.5 kg: 11.25 mg IM monthly
• Children weighing above 37.5 kg: 15 mg IM monthly

Lupron Depot-Ped (3-month dose)

• 11.25 mg or 30 mg as single IM injection every 3 months (dose not based on weight)

Leuprolide acetate

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

Fensolvi

• 45 mg SC once every 6 months

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Leuprolide include:

• hot flashes,
• sweating,
• acne,
• rash,
• itching,
• scaly skin,
• mood changes,
• headache,
• general pain,
• vaginal swelling, itching or discharge,
• breakthrough bleeding,
• weight gain,
• decreased testicle size, and
• redness, pain, swelling, or oozing at the injection site

Serious side effects of Leuprolide include:

• bone pain,
• loss of movement in any part of your body,
• swelling,
• rapid weight gain,
• convulsions (seizures),
• unusual changes in mood or behavior (crying spells, anger, feeling irritable),
• sudden chest pain or discomfort,
• wheezing,
• dry cough or hack,
• painful or difficult urination,
• increased thirst,
• increased urination,
• hunger,
• dry mouth,
• fruity breath odor,
• pain or unusual sensations in the back,
• numbness,
• weakness,
• a tingly feeling in the legs or feet,
• muscle weakness,
• loss of bowel or bladder control,
• chest pain or pressure,
• pain spreading to the jaw or shoulder,
• nausea,
• sweating,
• sudden numbness or weakness (especially on one side of the body),
• sudden severe headache, and
• slurred speech 

Rare side effects of Leuprolide include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Leuprolide has severe interactions with at least 30 other drugs.
• Leuprolide has serious interactions with the following drugs:
  • amisulpride
  • desflurane
  • deutetrabenazine
  • encorafenib
  • entrectinib
  • fexinidazole
  • glasdegib
  • inotuzumab
  • lefamulin
  • panobinostat
  • pitolisant
• Leuprolide has moderate interactions with at least 67 other drugs.
• Leuprolide has minor interactions with the following drugs:
  • maitake
  • taurine

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions, concerns.

Contraindications

• Hypersensitivity
• Pregnancy 

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Leuprolide?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Leuprolide?”

Cautions

• May cause fetal harm when administered to pregnant females
• Children and young adults
  • During the early phase of therapy, gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug; therefore, an increase in clinical signs and symptoms of puberty including vaginal bleeding may be observed during the first weeks of therapy or after subsequent doses
  • Psychiatric adverse events or emotional lability, including crying, irritability, impatience, anger, and aggression were reported; many, but not all, patients had a history of psychiatric illness or other comorbidities with an increased risk of depression
  • Postmarketing reports of convulsions reported, including patients with or without a history of seizures, epilepsy, cerebrovascular disorders, central nervous system anomalies, and patients on concomitant medications associated with convulsions such as bupropion and SSRIs
• Adults
• Spinal cord compression reported; observe patients closely for weakness and paresthesias in first few weeks of therapy; observe patients with metastatic vertebral lesions closely
• Tumor flare resulting from transient increases in testosterone, leading to bone pain, hematuria, bladder outlet obstruction, and neuropathy in prostate cancer patients reported during the first few weeks of therapy
• Closely observe patients for urinary tract obstruction and hematuria in the first few weeks of therapy
• Orchiectomy or luteinizing hormone agonists are recommended as initial treatment for androgen deprivation in patients with advanced androgen-sensitive prostate cancer
• Decrease in bone density reported when the drug is used for more than 6 months; use caution if there are additional risk factors for bone loss, including corticosteroid therapy or chronic alcohol use
• Worsening of endometriosis or uterine leiomyomata symptoms with therapy reported initially
• Rare cases of pituitary apoplexy, frequently secondary to pituitary adenoma reported (onset 1hr to usually less than 2 weeks): may present as sudden headache, vomiting, visual or mental status changes, and cardiovascular collapse (rare), requiring immediate medical attention
• 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 the treatment of hyperglycemia or diabetes
• Prostate cancer symptoms may worsen during the initial treatment period
• Androgen deprivation therapy may prolong the QT/QTc interval; consider whether benefits of androgen deprivation outweigh 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 a slightly increased risk of diabetes, heart attack, stroke, and sudden death
• In women, the duration of treatment with GnRH agonists does not exceed 1 year, except in the treatment of breast cancer
• Therapy for hormone receptor-positive breast cancer
• Ovarian suppression recommended for the following
  • Premenopausal women with the higher-risk disease in addition to adjuvant endocrine therapy,
  • Addition to adjuvant chemotherapy in premenopausal women with stage II or stage III breast cancers
  • Stage I or II breast cancers at higher risk of recurrence in addition to endocrine therapy, who might consider chemotherapy
  • Women with stage I disease, which does not require chemotherapy should receive endocrine therapy but not ovarian suppression
  • Women with node-negative cancers less than 1 cm (T1A is less than T1B) should receive endocrine therapy, but not ovarian suppression 

Pregnancy and Lactation

• Pregnancy
• Contraindicated
• Based on animal data and mechanism of action, fetal harm may occur
• Insufficient data available to assess the risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Exclude pregnancy in females of reproductive potential before initiation
• Contraception
  • Females of reproductive potential: Not a contraceptive; if contraception is indicated, use nonhormonal contraception during treatment
• Infertility
  • Based on its pharmacodynamic effects of decreasing secretion of gonadal steroids, fertility is expected to be decreased during treatment
  • Clinical and pharmacologic studies in adults (above 18 years) with leuprolide acetate and similar analogs have shown reversibility of fertility suppression when discontinued after continuous administration for periods of up to 24 weeks
  • There is no evidence that pregnancy rates are affected following discontinuation
  • Animal studies (prepubertal and adult rats and monkeys) with leuprolide acetate and other GnRH analogs have shown functional recovery of fertility suppression 
• Lactation
  • No data available on the presence of leuprolide acetate in either animal or human milk, effects on breastfed infants, or effects on milk production
  • Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed infant therapy or from underlying maternal conditions