Leuprolide Acetate
Kit · Subcutaneous
Uses
Leuprolide acetate injection is indicated in the palliative treatment of advanced prostatic cancer.
Dosage and administration
The recommended dose is 1 mg (0.2 mL or 20 unit mark) administered as a single daily subcutaneous injection. As with other drugs administered chronically by subcutaneous injection, the injection site should be varied periodically. Each 0.2 mL contains 1 mg of leuprolide acetate, sodium chloride for tonicity adjustment, 1.8 mg of benzyl alcohol as preservative and water for injection. The pH may have been adjusted with sodium hydroxide and/or acetic acid. Follow the pictorial directions on this package insert for administration. NOTE: As with all parenteral products, inspect the solution for discoloration and particulate matter before each use.
Contraindications
Leuprolide acetate injection is contraindicated in patients known to be hypersensitive to GnRH, GnRH agonist analogs or any of the excipients in leuprolide acetate injection. Reports of anaphylactic reactions to GnRH agonist analogs have been reported in the medical literature.
Warnings
Initially, leuprolide acetate injection, like other LH-RH agonists, causes increases in serum levels of testosterone. Transient worsening of symptoms, or the occurrence of additional signs and symptoms of prostate cancer, may develop during the first few weeks of leuprolide acetate injection treatment. Patients may experience a temporary increase in bone pain, which can be managed symptomatically. As with other LH-RH agonists, ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications. Safe use of leuprolide acetate in pregnancy has not been established clinically. Leuprolide acetate injection may cause fetal harm. Periodic monitoring of serum testosterone and prostate-specific antigen (PSA) levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. It should be noted that results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions. Severe Cutaneous Adverse Reactions Leuprolide acetate can cause severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). SCARs, including SJS/TEN, DRESS, and AGEP, occurred in patients receiving leuprolide acetate; including cases with visceral involvement and/or requiring skin grafts (see ADVERSE REACTIONS ). Monitor patients for the development of SCARs. If a SCAR is suspected, interrupt leuprolide acetate until the etiology of the reaction has been determined. Consultation with a dermatologist is recommended. If a SCAR is confirmed, or for other grade 4 skin reactions, permanently discontinue leuprolide acetate.
Precautions
Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy (see WARNINGS and ADVERSE REACTIONS sections). Patients with known allergies to benzyl alcohol, an ingredient of the drug's vehicle, may present symptoms of hypersensitivity, usually local, in the form of erythema and induration at the injection site. Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. 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. Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice. Based on findings in animal studies, leuprolide acetate injection may cause fetal harm when administered to a pregnant woman. In animal developmental and reproductive toxicology studies, administration of the monthly formulation of leuprolide acetate on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-fetal toxicity in animals at doses less than the human dose, based on body surface area, using an estimated daily dose. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus. Effect on QT/QTc Interval Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes. Information for Patients See INFORMATION FOR PATIENTS which appears after the REFERENCE section. Laboratory Tests Response to leuprolide acetate should be monitored by measuring serum levels of testosterone and prostate-specific antigen (PSA). In the majority of patients, testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment. Castrate levels were reached within two to four weeks and once attained were maintained for as long as drug administration continued. Drug Interactions See CLINICAL PHARMACOLOGY, Pharmacokinetics section. Drug/Laboratory Test Interactions Administration of leuprolide acetate in therapeutic doses results in suppression of the pituitary-gonadal system. Normal function is usually restored within 4 to 12 weeks after treatment is discontinued. Carcinogenesis, Mutagenesis, Impairment of Fertility Two-year carcinogenicity studies were conducted with leuprolide acetate in rats and mice. In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 mg/kg to 4 mg/kg). There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group). In mice, no pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years. Patients have been treated with leuprolide acetate for up to three years with doses as high as 10 mg/day and for two years with doses as high as 20 mg/day without demonstrable pituitary abnormalities. Mutagenicity studies have been performed with leuprolide acetate using bacterial and mammalian systems. These studies provided no evidence of a mutagenic potential. Leuprolide acetate injection may reduce male and female fertility. Administration of leuprolide acetate to male and female rats at dose of 0.024 mg/kg, 0.24 mg/kg, and 2.4 mg/kg as monthly depot formulation for up to 3 months (approximately as low as 1/30 of the human dose based on body surface area using an estimated daily dose in animals and humans) caused atrophy of the reproductive organs, and suppression of reproductive function. These changes were reversible upon cessation of treatment. Pregnancy Risk Summary Based on findings in animal studies and mechanism of action, leuprolide acetate injection may cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. In animal developmental and reproductive toxicology studies, administration of a monthly formulation of leuprolide acetate on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-fetal toxicity in animals at doses less than the human dose based on body surface area using an estimated daily dose (see data) . Advise pregnant patients and females of reproductive potential of the potential risk to the fetus. Data Animal Data Major fetal malformations were observed in developmental and reproductive toxicology studies in rabbits after a single administration of the monthly formulation of leuprolide acetate administered on day 6 of pregnancy at test dosages of 0.00024 mg/kg, 0.0024 mg/kg, and 0.024 mg/kg (approximately 1/600 to 1/6 the human dose based on body surface area using an estimated daily dose in animals and humans).
Side effects
Clinical Trials In the majority of patients testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment. This transient increase was occasionally associated with a temporary worsening of signs and symptoms, usually manifested by an increase in bone pain (see WARNINGS section). Cases of temporary worsening of existing hematuria and urinary tract obstruction have occurred during the first week. Temporary weakness and paresthesia of the lower limbs have been reported. Potential exacerbations of signs and symptoms during the first few weeks of treatment is a concern in patients with vertebral metastases and/or urinary obstruction which, if aggravated, may lead to neurological problems or increase the obstruction. In a comparative trial of leuprolide acetate injection versus DES, in 5% or more of the patients receiving either drug, the following adverse reactions were reported to have a possible or probable relationship to drug as ascribed by the treating physician. Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug related are excluded. Leuprolide Acetate Injection (N = 98) DES (N = 101) Number of Reports Cardiovascular System Congestive heart failure 1 5 ECG changes/ischemia 19 22 High blood pressure 8 5 Murmur 3 8 Peripheral edema 12 30 Phlebitis/thrombosis 2 10 Gastrointestinal System Anorexia 6 5 Constipation 7 9 Nausea/vomiting 5 17 Endocrine System *Decreased testicular size 7 11 *Gynecomastia/breast tenderness or pain 7 63 *Hot flashes 55 12 *Impotence 4 12 Hemic and Lymphatic System Anemia 5 5 Musculoskeletal System Bone pain 5 2 Myalgia 3 9 Central/Peripheral Nervous System Dizziness/lightheadedness 5 7 General pain 13 13 Headache 7 4 Insomnia/sleep disorders 7 5 Respiratory System Dyspnea 2 8 Sinus congestion 5 6 Integumentary System Dermatitis 5 8 Urogenital System Frequency/urgency 6 8 Hematuria 6 4 Urinary tract infection 3 7 Miscellaneous Asthenia 10 10 * Physiologic effect of decreased testosterone. In this same study, the following adverse reactions were reported in less than 5% of the patients on leuprolide acetate injection. Cardiovascular System – Angina, Cardiac arrhythmias, Myocardial infarction, Pulmonary emboli. Gastrointestinal System – Diarrhea, Dysphagia, Gastrointestinal bleeding, Gastrointestinal disturbance, Peptic ulcer, Rectal polyps. Endocrine System – Libido decrease, Thyroid enlargement. Musculoskeletal System – Joint pain. Central/Peripheral Nervous System – Anxiety, Blurred vision, Lethargy, Memory disorder, Mood swings, Nervousness, Numbness, Paresthesia, Peripheral neuropathy, Syncope/blackouts, Taste disorders. Respiratory System – Cough, Pleural rub, Pneumonia, Pulmonary fibrosis. Integumentary System – Carcinoma of skin/ear, Dry skin, Ecchymosis, Hair loss, Itching, Local skin reactions, Pigmentation, Skin lesions. Urogenital System – Bladder spasms, Dysuria, Incontinence, Testicular pain, Urinary obstruction. Miscellaneous – Depression, Diabetes, Fatigue, Fever/chills, Hypoglycemia, Increased BUN, Increased calcium, Increased creatinine, Infection/inflammation, Ophthalmologic disorders, Swelling (temporal bone). In an additional clinical trial and from long-term observation of both studies, the following additional adverse reactions were reported for patients receiving leuprolide acetate injection. Cardiovascular System – Bradycardia, Carotid bruit, Extrasystole, Palpitations, Perivascular cuffing (eyes), Ruptured aortic aneurysm, Stroke, Tachycardia, Transient ischemic attack. Gastrointestinal System – Flatus, Dryness of mouth and throat, Hepatitis, Hepatomegaly, Occult blood (rectal exam), Rectal fistula/erythema. Endocrine System – Libido increase, Thyroid nodule. Musculoskeletal System – Ankylosing spondylosis, Arthritis, Blurred disc margins, Bone fracture, Muscle stiffness, Muscle tenderness, Pelvic fibrosis, Spasms/cramps. Central/Peripheral Nervous System – Auditory hallucinations/tinnitus, Decreased hearing, Decreased reflexes, Euphoria, Hyperreflexia, Loss of smell, Motor deficiency. Respiratory System – Chest tightness, Decreased breathing sounds, Hemoptysis, Pleuritic chest pain, Pulmonary infiltrate, Rales/rhonchi, Rhinitis, Strep throat, Wheezing/bronchitis. Integumentary System – Boil (pubic), Bruises, Hives, Keratosis, Mole, Shingles, Spiders. Urogenital System – Blisters on penis, Inguinal hernia, Penile swelling, Post void residual, Prostatic pain, Pyuria. Miscellaneous – Abdominal distention, Facial swelling/edema, Feet burning, Flu, Eyelid growth, Hypoproteinemia, Accidental injury, Knee effusion, Mass, Pallid, Sallow, Weakness. Post-marketing During post-marketing surveillance which includes other dosage forms and other patient populations, the following adverse reactions were reported. Symptoms consistent with an anaphylactoid or asthmatic process have been rarely (incidence rate of about 0.002%) reported. Symptoms consistent with fibromyalgia (e.g., joint and muscle pain, headaches, sleep disorders, gastrointestinal distress and shortness of breath) have been reported individually and collectively. Cardiovascular System – Hypotension, Myocardial infarction, Pulmonary embolism. Endocrine System – Diabetes. Gastrointestinal System – Hepatic dysfunction. Hepato-biliary disorder – Serious drug-induced liver injury. Hemic and Lymphatic System – Decreased WBC. Skin and Subcutaneous Tissue Disorders – Rash, Urticaria, Photosensitivity, Hair growth, SJS/TEN, DRESS, AGEP, Dermatitis exfoliative, Bullous dermatitis, Erythema multiforme. Central/Peripheral Nervous System – Convulsion, Peripheral neuropathy, Spinal fracture/paralysis, Hearing disorder. Miscellaneous – Hard nodule in throat, Weight gain, Increased uric acid. Musculoskeletal System – Tenosynovitis-like symptoms. Respiratory System – Respiratory disorders, Interstitial lung disease.
Pregnancy
Drug Interactions See CLINICAL PHARMACOLOGY, Pharmacokinetics section. Pregnancy Risk Summary Based on findings in animal studies and mechanism of action, leuprolide acetate injection may cause fetal harm when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. In animal developmental and reproductive toxicology studies, administration of a monthly formulation of leuprolide acetate on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-fetal toxicity in animals at doses less than the human dose based on body surface area using an estimated daily dose (see data) . Advise pregnant patients and females of reproductive potential of the potential risk to the fetus. Data Animal Data Major fetal malformations were observed in developmental and reproductive toxicology studies in rabbits after a single administration of the monthly formulation of leuprolide acetate administered on day 6 of pregnancy at test dosages of 0.00024 mg/kg, 0.0024 mg/kg, and 0.024 mg/kg (approximately 1/600 to 1/6 the human dose based on body surface area using an estimated daily dose in animals and humans). Since a depot formulation was utilized in the study, a sustained exposure to leuprolide was expected throughout the period of organogenesis and to the end of gestation. Similar studies in rats did not demonstrate an increase in fetal malformations, however, there was increased fetal mortality and decreased fetal weights with the two higher doses of the monthly formulation of leuprolide acetate in rabbits and with the highest dose in rats.
Geriatric use
Geriatric Use In the clinical trials for leuprolide acetate injection, the majority (69%) of subjects studied were at least 65 years of age. Therefore, the labeling reflects the pharmacokinetics, efficacy and safety of leuprolide acetate injection in this population.
Overdosage
In rats subcutaneous administration of 250 to 500 times the recommended human dose, expressed on a per body weight basis, resulted in dyspnea, decreased activity and local irritation at the injection site. There is no evidence at present that there is a clinical counterpart of this phenomenon. In early clinical trials with leuprolide acetate doses as high as 20 mg/day for up to two years caused no adverse effects differing from those observed with the 1 mg/day dose.
Description
Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin releasing hormone (GnRH or LH-RH). The analog possesses greater potency than the natural hormone. The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl- N -ethyl-L-prolinamide acetate (salt). It has a molecular formula C 59 H 84 N 16 O 12 and the molecular weight 1209.4. The chemical structure is: Leuprolide Acetate Injection is a sterile, aqueous, clear, colorless solution intended for subcutaneous injection. It is available in a 2.8 mL multiple-dose vial containing leuprolide acetate USP, 5 mg/mL (equivalent to 4.75 mg leuprolide free base), sodium chloride (6.3 mg/mL) for tonicity adjustment, benzyl alcohol as a preservative (9 mg/mL), and water for injection. The pH may have been adjusted with sodium hydroxide and/or acetic acid. 1
How supplied
Leuprolide Acetate Injection is a sterile, clear, colorless solution supplied in a 2.8 mL multiple-dose vial. The vial is packaged as follows: 14 Day Patient Administration Kit with 14 disposable syringes with fixed needles and 28 alcohol swabs. The packaging is available as below: One Leuprolide Acetate Injection 2.8 mL Multiple-Dose Vial is packaged in a 14 Days Kit: NDC 70121-2537-6 Store below 77°F (25°C). Do not freeze. Protect from light; store vial in carton until use.
Patient information
Be sure to consult your physician with any questions you may have or for information about leuprolide acetate injection and its use. WHAT IS LEUPROLIDE ACETATE INJECTION? Leuprolide acetate injection is chemically similar to gonadotropin releasing hormone (GnRH or LH-RH) a hormone which occurs naturally in your body. Normally, your body releases small amounts of LH-RH and this leads to events which stimulate the production of sex hormones. However, when you inject leuprolide acetate injection, the normal events that lead to sex hormone production are interrupted and testosterone is no longer produced by the testes. Leuprolide acetate injection must be injected because, like insulin which is injected by diabetics, leuprolide acetate is inactive when taken by mouth. If you were to discontinue the drug for any reason, your body would begin making testosterone again. DIRECTIONS FOR USING LEUPROLIDE ACETATE INJECTION 1. Wash hands thoroughly with soap and water. 2. When using a new vial of leuprolide acetate injection flip off the plastic cover to expose the grey rubber stopper. Wipe metal ring and rubber stopper with an alcohol wipe each time you use leuprolide acetate injection. Check the liquid in the vial for particulate matter and discoloration prior to use. DO NOT USE if the liquid is not clear or has particles and replace with a new vial. 3. Remove needle cap and inject the needle in the center of the rubber stopper on the leuprolide acetate injection vial. 4. Take cover off needle. Push the needle through the center of the rubber stopper on the leuprolide acetate injection vial. 5. Push the plunger all the way in to inject air into the vial. 6. Keep the needle in the vial and turn the vial upside down. Check to make sure the tip of the needle is in the liquid. Slowly pull back on the plunger, until the syringe fills to the 0.2 mL or 20 unit mark. 7. Toward the end of a two-week period, the amount of leuprolide acetate injection left in the vial will be small. Take special care to hold the vial straight and to keep the needle tip in liquid while pulling back on the plunger. 8. Keeping the needle in the vial and the vial upside down, check for air bubbles in the syringe. If you see any, push the plunger slowly in to push the air bubble back into the vial. Keep the tip of the needle in the liquid and pull the plunger back again to fill to the 0.2 mL or 20 unit mark. 9. Do this again if necessary to eliminate air bubbles. 10. To protect your skin, inject each daily dose at a different injection site. 11. Choose an injection site. Cleanse the injection site with another alcohol wipe. 12. Hold the syringe in one hand. Hold the skin taut, or pull up a little flesh with the other hand, as you were instructed. 13. Holding the syringe as you would a pencil, inject the needle all the way into the skin at a 90° angle. Push the plunger to administer the injection. 14. Hold an alcohol wipe down on your skin where the needle is inserted and withdraw the needle at the same angle it was inserted. 15. Use the disposable syringe only once and dispose of it properly as you were instructed. Needles thrown into a garbage bag could accidentally stick someone. NEVER LEAVE SYRINGES, NEEDLES OR DRUGS WHERE CHILDREN CAN REACH THEM. SOME SPECIAL ADVICE You may experience hot flashes when using leuprolide acetate injection. During the first few weeks of treatment you may experience increased bone pain, increased difficulty in urinating, and less commonly but most importantly, you may experience the onset or aggravation of nerve symptoms. In any of these events, discuss the symptoms with your doctor. Like other treatment options, leuprolide acetate injection may cause impotence. Notify your doctor if you develop new or worsened symptoms after beginning leuprolide acetate injection treatment. You may experience some irritation at the injection site, such as burning, itching or swelling. These reactions are usually mild and go away. If they do not, tell your doctor. If you have experienced an allergic reaction to other drugs like leuprolide acetate injection, you should not use this drug. Do not stop taking your injections because you feel better. You need an injection every day to make sure leuprolide acetate injection keeps working for you. If you need to use an alternate to the syringe supplied with leuprolide acetate injection, low-dose insulin syringes should be utilized. When the drug level gets low, take special care to hold the vial straight up and down and to keep the needle tip in liquid while pulling back on the plunger. Do not try to get every last drop out of the vial. This will increase the possibility of drawing air into the syringe and getting an incomplete dose. Some extra drug has been provided so that you can withdraw the recommended number of doses. Tell your pharmacist when you will need leuprolide acetate injection so it will be at the pharmacy when you need it. Store below 77°F (25°C). Do not store near a radiator or other very warm place. Do not freeze. Protect from light; store vial in carton until use. Do not leave your drug or hypodermic syringes where anyone can pick them up. Keep this and all other medications out of reach of children. To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Manufactured by: Amneal Pharmaceuticals Pvt. Ltd. Ahmedabad 382213, INDIA Or Amneal Pharmaceuticals Pvt. Ltd. Ahmedabad 382110, INDIA Distributed by: Amneal Pharmaceuticals LLC Bridgewater, NJ 08807 Rev. 05-2026-05
Label text from the FDA structured product label by Amneal Pharmaceuticals LLC (revised May 28, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Leuprolide Acetate in 1 product
Leuprolide Acetate NDC products (12)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 70121-2537 | Kit | Amneal Pharmaceuticals LLC | ANDA |
| 42023-259 | Leuprolide Acetate 1 mg/.2mL Injection | Endo USA, Inc. | ANDA |
| 55150-478 | Kit | Eugia US LLC | ANDA |
| 71288-569 | Kit | Meitheal Pharmaceuticals Inc | ANDA |
| 72603-344 | Kit | NorthStar RxLLC | ANDA |
| 0121-2106 | Kit | PAI Holdings, LLC dba PAI Pharma | ANDA |
| 0781-4003 | Kit | Sandoz Inc | ANDA |
| 47335-936 | Kit | Sun Pharmaceutical Industries, Inc. | ANDA |
| 72843-591 | Kit | UBI Pharma Inc. | ANDA |
| 72664-611 | Kit | VGYAAN Pharmaceuticals LLC | ANDA |
| 70771-1687 | Kit | Zydus Lifesciences Limited | ANDA |
| 70710-1769 | Kit | Zydus Pharmaceuticals USA Inc. | ANDA |
Frequently asked questions
What is Leuprolide Acetate used for?
Leuprolide acetate injection is indicated in the palliative treatment of advanced prostatic cancer.
What are the side effects of Leuprolide Acetate?
Clinical Trials In the majority of patients testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment. This transient increase was occasionally associated with a temporary worsening of signs and symptoms, usually manifested by an increase in bone pain (see WARNINGS section). Cases of temporary… See the full label for the complete list.
Who makes Leuprolide Acetate?
Leuprolide Acetate is listed by 12 labelers in the FDA NDC directory, including Amneal Pharmaceuticals LLC, Endo USA, Inc., Eugia US LLC, Meitheal Pharmaceuticals Inc.