Lupron Depot

GENERIC AVAILABLE: Yes.

The most common side effects of leuprolide are:

• aches and pain,
• fatigue,
• edema,
• headaches,
• hot flashes,
• chest pain, and
• irritation at the injection site.

Other important side effects of leuprolide include:

• impotence,
• shrinking of the testes, and
• breast enlargement in men (gynecomastia).

Depression, rare cases of suicidal behavior, low blood pressure, convulsions, joint pain and muscle aches have been reported in post-marketing surveillance.

Leuprolide can harm an unborn baby or cause birth defects. Do not use if you are pregnant.

You should not breast-feed while you are using leuprolide.

You should not use this medication if you are allergic to leuprolide or similar medications such as buserelin (Suprefact, Suprecor), goserelin (Zoladex), histrelin (Supprelin, Vantas), or nafarelin (Synarel).

You should not use leuprolide if you have abnormal vaginal bleeding that has not been diagnosed by a doctor.

Before using leuprolide, tell your doctor if you have epilepsy, asthma, migraines, heart or kidney disease, a history of depression, osteoporosis, bone cancer affecting your spine, blood in your urine, or if you are unable to urinate.

Tell your doctor if you have a personal or family history of osteoporosis, or if you have any risk factors for bone loss such as smoking, alcohol use, or taking steroid or seizure medications long term. Long-term use of this medication may decrease bone density, possibly leading to osteoporosis.

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

Certain brands or strengths of leuprolide are only for men.

Your symptoms may become temporarily worse when you first start using leuprolide. Tell your doctor if this continues for longer than 2 months.

Call your doctor at once if you have a seizure, or unusual changes in mood or behavior.

Do not use if you are pregnant.

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

In the U.S.

• Eligard
• Lupron
• Lupron Depot
• Lupron Depot-Ped
• Viadur

Available Dosage Forms:

• Powder for Suspension, 3 Month
• Solution
• Powder for Suspension, 1 Month
• Powder for Suspension, 4 Month
• Powder for Suspension, 6 Month
• Powder for Solution
• Kit
• Powder for Suspension

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Luteinizing Hormone Releasing Hormone Agonist

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.

Lupron Depot must be administered under the supervision of a physician.

In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of metastatic castration-resistant prostate cancer.

Lupron Depot 7.5 mg for 1-Month Administration

The recommended dose of Lupron Depot 7.5 mg for 1-month administration is one injection every 4 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics.

Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted and should be administered every 4 weeks as a single intramuscular injection.

For optimal performance of the prefilled dual chamber syringe (PDS), read and follow the instructions in Section 2.5.

Lupron Depot 22.5 mg for 3-Month Administration

The recommended dose of Lupron Depot 22.5 mg for 3-month administration is one injection every 12 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics.

Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted and should be administered every 12 weeks as a single intramuscular injection.

For optimal performance of the prefilled dual chamber syringe (PDS), read and follow the instructions in Section 2.5.

Lupron Depot 30 mg for 4-Month Administration

The recommended dose of Lupron Depot 30 mg for 4-month administration is one injection every 16 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics.

Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted and should be administered every 16 weeks as a single intramuscular injection.

For optimal performance of the prefilled dual chamber syringe (PDS), read and follow the instructions in Section 2.5.

Lupron Depot 45 mg for 6-Month Administration

The recommended dose of Lupron Depot 45 mg for 6-month administration is one injection every 24 weeks. Do not use concurrently a fractional dose, or a combination of doses of this or any depot formulation due to different release characteristics.

Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted and should be administered every 24 weeks as a single intramuscular injection.

For optimal performance of the prefilled dual chamber syringe (PDS), read and follow the instructions in Section 2.5.

Reconstitution and Administration for Injection of Lupron Depot

• Reconstitute and administer the lyophilized microspheres as a single intramuscular injection.
• Inject the suspension immediately or discard if not used within two hours, because Lupron Depot does not contain a preservative.

1. Visually inspect the Lupron Depot powder. DO NOT USE the syringe if clumping or caking is evident. A thin layer of powder on the wall of the syringe is considered normal prior to mixing with the diluent. The diluent should appear clear and colorless.
2. To prepare for injection, screw the white plunger into the end stopper until the stopper begins to turn (see Figure 1 and Figure 2).

   Figure 1

   Figure 2

3. Hold the syringe UPRIGHT. Release the diluent by SLOWLY PUSHING (6 to 8 seconds) the plunger until the first middle stopper is at the blue line in the middle of the barrel (see Figure 3).

   Figure 3

4. Keep the syringe UPRIGHT. Mix the microspheres (powder) thoroughly by gently shaking the syringe until the powder forms a uniform suspension. The suspension will appear milky. If the powder adheres to the stopper or caking/clumping is present, tap the syringe with your finger to disperse. DO NOT USE if any of the powder has not gone into suspension (see Figure 4).

   Figure 4

5. Keep the syringe UPRIGHT. With the opposite hand pull the needle cap upward without twisting.
6. Keep the syringe UPRIGHT. Advance the plunger to expel the air from the syringe. Now the syringe is ready for injection.
7. After cleaning the injection site with an alcohol swab, administer the intramuscular injection by inserting the needle at a 90 degree angle into the gluteal area, anterior thigh, or deltoid; injection sites should be alternated (see Figure 5).

   Figure 5

   NOTE: If a blood vessel is accidentally penetrated, aspirated blood will be visible just below the luer lock (see Figure 6) and can be seen through the transparent LuproLoc® safety device. If blood is present, remove the needle immediately. Do not inject the medication.

   Figure 6

8. Inject the entire contents of the syringe intramuscularly.
9. Withdraw the needle. Once the syringe has been withdrawn, immediately activate the LuproLoc® safety device by pushing the arrow on the lock upward towards the needle tip with the thumb or finger, as illustrated, until the needle cover of the safety device over the needle is fully extended and a CLICK is heard or felt (see Figure 7).

   Figure 7

   10. Dispose of the syringe according to local regulations/procedures.

No pharmacokinetic-based drug-drug interaction studies have been conducted with Lupron Depot.

Drug/Laboratory Test Interactions

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

Carcinogenesis, Mutagenesis, Impairment of Fertility

Two-year carcinogenicity studies were conducted 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 daily doses (0.6 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 leuprolide acetate-induced tumors or 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.

Genotoxicity studies were conducted with leuprolide acetate using bacterial and mammalian systems. These studies provided no evidence of mutagenic effects or chromosomal aberrations.

Leuprolide may reduce male and female fertility. Administration of leuprolide acetate to male and female rats at dose of 0.024, 0.24, 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.