Lupron Depot-Ped

Leuprolide injection: 5 mg/ml and 3.75 mg . Lupron Depot microspheres for injection: 3.75, 7.5, 15, 11.25, 22.5, 30, and 45 mg/vial.

Leuprolide should be stored at room temperature, between 15 C to 30 C (59 F to 86 F).

You should not use this medicine if you are allergic to leuprolide or similar medicines such as buserelin, goserelin, histrelin, nafarelin, or if you have abnormal vaginal bleeding that has not been checked by a doctor.

Certain brands or strengths of leuprolide are used to treat only men and should not be used in women or children. Always check your medicine to make sure you have received the correct brand and strength.

Leuprolide can cause birth defects. Do not use if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

To make sure leuprolide is safe for you, tell your doctor if you have ever had:

• depression, mental illness or psychosis;

• seizures or epilepsy;

• a brain tumor or blood vessel disorder;

• heart disease, congestive heart failure, long QT syndrome;

• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood); or

• risk factors for bone loss (personal or family history of osteoporosis, smoking, alcohol use, taking steroid or seizure medicines long term).

Leuprolide usually causes women to stop ovulating or having menstrual periods. However, you may still be able to get pregnant. Use a barrier form of birth control (condom or diaphragm with spermicide). Hormonal contraception (birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective enough to prevent pregnancy during your treatment.

Call your doctor if your periods continue while you are being treated with this medicine.

It is not known whether leuprolide passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Leuprolide injection is a synthetic (man-made) hormone that is similar to a natural hormone that is produced in the brain. It is used to treat a number of medical problems including:

• Anemia caused by bleeding from uterine leiomyomas (fibroid tumors in the uterus), or
• Cancer of the prostate that is advanced or late-stage, or
• Central precocious puberty, a condition which causes early puberty in boys (before 9 years of age) and girls (before 8 years of age), or
• Pain due to endometriosis.

When given regularly to men, leuprolide decreases testosterone levels. Reducing the amount of testosterone in the body helps treat cancer of the prostate.

When given regularly to women, leuprolide decreases estrogen levels. Reducing the amount of estrogen in the body helps treat endometriosis. Leuprolide will also shrink tumors in the uterus, which decreases vaginal bleeding and helps prevent anemia.

When given regularly to boys and girls who have early puberty, leuprolide slows the development of the genital area for both sexes. Leuprolide will also slow breast development in girls. This medicine will delay puberty only as long as the child continues to receive it.

This medicine is available only with your doctor's prescription.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of leuprolide pediatric injection in children. However, use is not recommended in children younger than 2 years of age. Leuprolide pediatric injection will stop having an effect for central precocious puberty soon after the child stops using it, and puberty will advance normally.

Appropriate studies have not been performed on the relationship of age to the effects of Eligard®, Lupron®, Lupron Depot®, Lupron Depot®-3 month, Lupron Depot®-4 month, Lupron Depot®-6 month, or Viadur® in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Eligard®, Lupron®, Lupron Depot®, Lupron Depot®-3 month, Lupron Depot®-4 month, or Lupron Depot®-6 month in the elderly.

No information is available on the relationship of age to the effects of Lupron Depot-Ped® or Viadur® in the elderly.

Pregnancy

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Mesoridazine
• Pimozide
• Piperaquine
• Saquinavir
• Sparfloxacin
• Terfenadine
• Thioridazine
• Ziprasidone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfuzosin
• Amiodarone
• Amitriptyline
• Anagrelide
• Apomorphine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Asenapine
• Astemizole
• Atazanavir
• Azithromycin
• Bedaquiline
• Chloroquine
• Chlorpromazine
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clozapine
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Dasatinib
• Delamanid
• Desipramine
• Deutetrabenazine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Droperidol
• Ebastine
• Efavirenz
• Eribulin
• Erythromycin
• Escitalopram
• Famotidine
• Felbamate
• Fingolimod
• Flecainide
• Fluconazole
• Fluoxetine
• Formoterol
• Foscarnet
• Fosphenytoin
• Galantamine
• Gatifloxacin
• Gemifloxacin
• Granisetron
• Halofantrine
• Haloperidol
• Hydroquinidine
• Hydroxychloroquine
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Itraconazole
• Ivabradine
• Ketoconazole
• Lapatinib
• Levofloxacin
• Lumefantrine
• Mefloquine
• Methadone
• Metronidazole
• Mifepristone
• Mizolastine
• Moxifloxacin
• Nelfinavir
• Nilotinib
• Norfloxacin
• Octreotide
• Ofloxacin
• Olanzapine
• Ondansetron
• Paliperidone
• Panobinostat
• Paroxetine
• Pasireotide
• Pazopanib
• Pentamidine
• Perphenazine
• Pimavanserin
• Pipamperone
• Pitolisant
• Posaconazole
• Probucol
• Procainamide
• Prochlorperazine
• Promethazine
• Propafenone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Ranolazine
• Ribociclib
• Rilpivirine
• Risperidone
• Ritonavir
• Sertindole
• Sevoflurane
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Solifenacin
• Sorafenib
• Sotalol
• Sulpiride
• Sunitinib
• Tacrolimus
• Tamoxifen
• Telaprevir
• Telavancin
• Telithromycin
• Tetrabenazine
• Tizanidine
• Tolterodine
• Toremifene
• Trazodone
• Trimipramine
• Vandetanib
• Vardenafil
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vinflunine
• Voriconazole
• Vorinostat
• Zuclopenthixol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Benzyl alcohol allergy—One of the Lupron® injection products for children may cause an allergic reaction.

• Brain tumors, history of or
• Congestive heart failure or
• Electrolyte imbalance (eg, low magnesium, potassium, or calcium) or
• Heart attack, history of or
• Heart or blood vessel disease or
• Heart rhythm problems (eg, congenital long QT syndrome)
• Seizures or epilepsy, history of or
• Stroke, history of—Use with caution. May cause side effects to become worse.

• Depression, history of or
• Diabetes or
• Hyperglycemia (high sugar in the blood) or
• Mental illness, history of or
• Osteoporosis (thinning of the bones)—Use with caution. May make these conditions worse.

The most common adverse reactions with GnRH agonists including Lupron Depot-PED 7.5 mg, 11.25 mg, or 15 mg for 1-month administration and Lupron Depot-PED 11.25 mg or 30 mg for 3-month administration are injection site reactions/pain including abscess, general pain, headache, emotional lability and hot flushes/sweating.

During the early phase of therapy, gonadotropins and sex steroids rise above baseline because of the initial stimulatory effect of the drug (hormonal flare effect). Therefore, an increase in clinical signs and symptoms of puberty may be observed [see Warnings and Precautions (5.1)].

Lupron Depot-PED 7.5 mg, 11.25 mg, or 15 mg for 1-month administration - Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

In two studies of children with central precocious puberty, in 2% or more of the patients receiving the drug, the following adverse reactions were reported to have a possible or probable relationship to drug as ascribed by the treating physician. Reactions which are not considered drug-related are excluded.

Less Common Adverse Reactions

The following treatment-emergent adverse reactions were reported in less than 2% of the patients and are listed below by body system.

Body as a Whole – aggravation of preexisting tumor and decreased vision, allergic reaction, body odor, fever, flu syndrome, hypertrophy, infection; Cardiovascular System – bradycardia, hypertension, peripheral vascular disorder, syncope; Digestive System – constipation, dyspepsia, dysphagia, gingivitis, increased appetite, nausea/vomiting; Endocrine System – accelerated sexual maturity, feminization, goiter; Hemic and Lymphatic System – purpura; Metabolic and Nutritional Disorders – growth retarded, peripheral edema, weight gain; Musculoskeletal System – arthralgia, joint disorder, myalgia, myopathy; Nervous System – hyperkinesia, somnolence; Psychiatric System – depression, nervousness; Respiratory System – asthma, epistaxis, pharyngitis, rhinitis, sinusitis; Integumentary System (Skin and Appendages) – alopecia, hair disorder, hirsutism, leukoderma, nail disorder, skin hypertrophy; Urogenital System – cervix disorder/neoplasm, dysmenorrhea, gynecomastia/breast disorders, menstrual disorder, urinary incontinence.

Laboratory: The following laboratory events were reported as adverse reactions: antinuclear antibody present and increased sedimentation rate.

Lupron Depot-PED 11.25 mg or 30 mg for 3-month administration - Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Less Common Adverse Reactions

The following treatment-emergent adverse reactions were reported in one patient and are listed below by system organ class:

Gastrointestinal Disorders – abdominal pain, nausea; General Disorders and Administration Site Conditions – asthenia, gait disturbance, injection site abscess sterile, injection site hematoma, injection site induration, injection site warmth, irritability; Metabolic and Nutritional Disorders – decreased appetite, obesity; Musculoskeletal and Connective Tissue Disorders - musculoskeletal pain, pain in extremity; Nervous System Disorders – dizziness; Psychiatric Disorders – crying, tearfulness; Respiratory, Thoracic and Mediastinal Disorders – cough; Skin and Subcutaneous Tissue Disorders – hyperhidrosis; Vascular Disorders – pallor.

Postmarketing

The following adverse events have been observed with this or other formulations of leuprolide acetate injection. As leuprolide has multiple indications, and therefore patient populations, some of these adverse events may not be applicable to every patient.

Allergic reactions (anaphylactic, rash, urticaria, and photosensitivity reactions) have also been reported.

Gastrointestinal Disorders: nausea, abdominal pain, vomiting;

General Disorders and Administration Site Conditions: chest pain, injection site reactions including induration and abscess have been reported;

Investigations: decreased WBC, weight increased;

Metabolism and Nutrition Disorders: diabetes mellitus;

Musculoskeletal and Connective Tissue Disorders: tenosynovitis-like symptoms;

Psychiatric Disorders: Emotional lability, such as crying, irritability, impatience, anger, and aggression has been observed with GnRH agonists, including Lupron Depot-PED [see Warnings and Precautions (5.2)]; Depression, including rare reports of suicidal ideation and attempt, has been reported for GnRH agonists, including Lupron Depot-PED, in children treated for central precocious puberty. Many, but not all, of these patients had a history of psychiatric illness or other comorbidities with an increased risk of depression.

Nervous System Disorders: neuropathy peripheral, convulsion [see Warnings and Precautions (5.3)], spinal fracture/paralysis;

Skin and Subcutaneous Tissue Disorders: hot flush, flushing, hyperhidrosis;

Reproductive System and Breast Disorders: prostate pain;

Vascular Disorders: hypertension, hypotension.

Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

See other LUPRON DEPOT and LUPRON Injection package inserts for other events reported in different patient populations.

No pharmacokinetic-based drug-drug interaction studies have been conducted; however, drug interactions are not expected to occur [see Clinical Pharmacology (12.3)].

Drug/Laboratory Test Interactions

Administration of Lupron Depot-PED in therapeutic doses results in suppression of the pituitary-gonadal system. Therefore, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and up to six months after discontinuation of Lupron Depot-PED may be affected. Normal pituitary-gonadal function is usually restored within six months after treatment with Lupron Depot-PED is discontinued.