LUPRON DEPOT (leuprolide Acetate For Depot Suspension)
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to useLUPRON DEPOT safely and effectively. See full prescribing informationfor LUPRON DEPOT.LUPRON DEPOT (leuprolide acetate for depot suspension)Initial U.S. Approval: 1989 -----------------------------RECENT MAJOR CHANGES------------------------Warnings and Precautions, Convulsions. (5.5)7/2013Warnings and Precautions, Effect on QT/QTc Interval. (5.4)6/2014---------------------------INDICATIONS AND USAGE---------------------------LUPRON DEPOT is a gonadotropin releasing hormone (GnRH) agonistindicated for: palliative treatment of advanced prostatic cancer. (1)--------------------------DOSAGE AND ADMINISTRATION-------------------LUPRON DEPOT must be administered under the supervision of a physician.Due to different release characteristics, the dosage strengths are not additiveand must be selected based upon the desired dosing schedule. (2) LUPRON DEPOT 7.5 mg for 1-month administration, given as a singleintramuscular injection every 4 weeks. (2.1) LUPRON DEPOT 22.5 mg for 3-month administration, given as a singleintramuscular injection every 12 weeks. (2.2) LUPRON DEPOT 30 mg for 4-month administration, given as a singleintramuscular injection every 16 weeks. (2.3) LUPRON DEPOT 45 mg for 6-month administration, given as a singleintramuscular injection every 24 weeks. (2.4)-------------------------DOSAGE FORMS AND STRENGTHS-----------------7.5 mg, 22.5 mg, 30 mg, and 45 mg injections in a kit with prefilled dualchamber syringe. S----------------------------- Hypersensitivity to GnRH, GnRH agonist or any of the excipients inLUPRON DEPOT. (4) Pregnancy. (4, 8.1)-------------------------WARNINGS AND PRECAUTIONS--------------------- Increased serum testosterone ( 50% above baseline) during first weekof treatment; monitor serum testosterone and PSA. (5.1, 5.6)oIsolated cases of transient worsening of symptoms, or additionalsigns and symptoms of prostate cancer during the first few weeksof treatment. (5.1)oA small number of patients may experience a temporary increasein bone pain which can be managed symptomatically. (5.1)oIsolated cases of ureteral obstruction and spinal cord compressionhave been reported with GnRH agonists, which may contribute toparalysis with or without fatal complications. (5.1)FULL PRESCRIBING INFORMATION: CONTENTS*1 INDICATIONS AND USAGE2 DOSAGE AND ADMINISTRATION2.1 LUPRON DEPOT 7.5 mg for 1-Month Administration2.2 LUPRON DEPOT 22.5 mg for 3-Month Administration2.3 LUPRON DEPOT 30 mg for 4-Month Administration2.4 LUPRON DEPOT 45 mg for 6-Month Administration2.5 Reconstitution and Administration for Injection of LUPRON DEPOT3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Tumor Flare5.2 Hyperglycemia and Diabetes5.3 Cardiovascular Diseases5.4 Effect on QT/QTc Interval5.5 Convulsions5.6 Laboratory Tests6 ADVERSE REACTIONS6.1 LUPRON DEPOT 7.5 mg for 1-Month Administration6.2 LUPRON DEPOT 22.5 mg for 3-Month Administration6.3 LUPRON DEPOT 30 mg for 4-Month Administration6.4 LUPRON DEPOT 45 mg for 6-Month Administration6.5 Postmarketing7 DRUG INTERACTIONS Hyperglycemia and Diabetes: Hyperglycemia and an increased risk ofdeveloping diabetes have been reported in men receiving GnRH analogs.Monitor blood glucose level and manage according to current clinicalpractice. (5.2)Cardiovascular Diseases: Increased risk of myocardial infarction, suddencardiac death and stroke has been reported in association with use ofGnRH analogs in men. Monitor for cardiovascular disease and manageaccording to current clinical practice. (5.3)Effect on QT/QTc Interval: Androgen deprivation therapy may prolongthe QT interval. Consider risks and benefits. (5.4)Convulsions have been observed in patients with or without a history ofpredisposing factors. Manage convulsions according to the currentclinical practice. (5.5)-----------------------------ADVERSE REACTIONS------------------------------- LUPRON DEPOT 7.5 mg for 1-month administration: The mostcommon adverse reactions ( 10%) were general pain, hotflashes/sweats, GI disorders, edema, respiratory disorder, urinarydisorder. (6.1) LUPRON DEPOT 22.5 mg for 3-month administration: The mostcommon adverse reactions ( 10%) were general pain, injection sitereaction, hot flashes/sweats, GI disorders, joint disorders, testicularatrophy, urinary disorders. (6.2) LUPRON DEPOT 30 mg for 4-month administration: The mostcommon adverse reactions ( 10%) were asthenia, flu syndrome, generalpain, headache, injection site reaction, hot flashes/sweats, GI disorders,edema, skin reaction, urinary disorders. (6.3) LUPRON DEPOT 45 mg for 6-month administration: The mostcommon adverse reactions ( 10%) were hot flush, injection site pain,upper respiratory infection, and fatigue. (6.4)In postmarketing experience, mood swings, depression, rare reports of suicidalideation and attempt, rare reports of pituitary apoplexy, and rare reports ofserious drug-induced liver injury have been reported. (6.5)To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc.at1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch------------------------USE IN SPECIFIC POPULATIONS---------------------- Pediatric: These LUPRON DEPOT formulations are not indicated foruse in children. See the LUPRON DEPOT PED package insert for theuse of leuprolide acetate in children with central precocious puberty. Geriatric: This label reflects clinical trials for LUPRON DEPOT inprostate cancer in which the majority of the subjects studied were atleast 65 years of age.See 17 for PATIENT COUNSELING INFORMATION.Revised: 06/20147.1 Drug/Laboratory Test Interactions8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Males of Reproductive Potential10 OVERDOSAGE11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility14 CLINICAL STUDIES14.1 LUPRON DEPOT 7.5 mg for 1-Month Administration14.2 LUPRON DEPOT 22.5 mg for 3-Month Administration14.3 LUPRON DEPOT 30 mg for 4-Month Administration14.4 LUPRON DEPOT 45 mg for 6-Month Administration16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are notlisted.
FULL PRESCRIBING INFORMATION1 INDICATIONS AND USAGELUPRON DEPOT 7.5 mg for 1-month administration, 22.5 mg for 3-month administration, 30mg for 4-month administration, and 45 mg for 6-month administration (leuprolide acetate) areindicated in the palliative treatment of advanced prostatic cancer.LUPRON DEPOT is a gonadotropin releasing hormone (GnRH) agonist.2 DOSAGE AND ADMINISTRATIONLUPRON DEPOT must be administered under the supervision of a physician.Table 1. LUPRON DEPOT Recommended Dosing7.5 mg for 1-Month 22.5 mg for 3-Month 30 mg for 4-Month45 mg for ationAdministrationRecommended 1 injection every 41 injection every 121 injection every 161 injection every 24 weeksdoseweeksweeksweeks2.1 LUPRON DEPOT 7.5 mg for 1-Month AdministrationThe recommended dose of LUPRON DEPOT 7.5 mg for 1-month administration is one injectionevery 4 weeks. Do not use concurrently a fractional dose, or a combination of doses of this orany depot formulation due to different release characteristics.Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted andshould be administered every 4 weeks as a single intramuscular injection.For optimal performance of the prefilled dual chamber syringe (PDS), read and follow theinstructions in Section 2.5.2.2 LUPRON DEPOT 22.5 mg for 3-Month AdministrationThe recommended dose of LUPRON DEPOT 22.5 mg for 3-month administration is oneinjection every 12 weeks. Do not use concurrently a fractional dose, or a combination of doses ofthis or any depot formulation due to different release characteristics.Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted andshould be administered every 12 weeks as a single intramuscular injection.
For optimal performance of the prefilled dual chamber syringe (PDS), read and follow theinstructions in Section 2.5.2.3 LUPRON DEPOT 30 mg for 4-Month AdministrationThe recommended dose of LUPRON DEPOT 30 mg for 4-month administration is one injectionevery 16 weeks. Do not use concurrently a fractional dose, or a combination of doses of this orany depot formulation due to different release characteristics.Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted andshould be administered every 16 weeks as a single intramuscular injection.For optimal performance of the prefilled dual chamber syringe (PDS), read and follow theinstructions in Section 2.5.2.4 LUPRON DEPOT 45 mg for 6-Month AdministrationThe recommended dose of LUPRON DEPOT 45 mg for 6-month administration is one injectionevery 24 weeks. Do not use concurrently a fractional dose, or a combination of doses of this orany depot formulation due to different release characteristics.Incorporated in a depot formulation, the lyophilized microspheres must be reconstituted andshould be administered every 24 weeks as a single intramuscular injection.For optimal performance of the prefilled dual chamber syringe (PDS), read and follow theinstructions in Section 2.5.2.5 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 LUPRONDEPOT does not contain a preservative.1. Visually inspect the LUPRON DEPOT powder. DO NOT USE the syringe if clumping orcaking is evident. A thin layer of powder on the wall of the syringe is considered normalprior 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 beginsto turn (see Figure 1 and Figure 2).
Figure 1Figure 23. 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 (seeFigure 3).Figure 34. Keep the syringe UPRIGHT. Mix the microspheres (powder) thoroughly by gently shakingthe 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 yourfinger to disperse. DO NOT USE if any of the powder has not gone into suspension (seeFigure 4).
Figure 45. Keep the syringe UPRIGHT. With the opposite hand pull the needle cap upward withouttwisting.6. Keep the syringe UPRIGHT. Advance the plunger to expel the air from the syringe. Now thesyringe is ready for injection.7. After cleaning the injection site with an alcohol swab, administer the intramuscular injectionby 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 5NOTE: If a blood vessel is accidentally penetrated, aspirated blood will be visible just belowthe luer lock (see Figure 6) and can be seen through the transparent LuproLoc safetydevice. If blood is present, remove the needle immediately. Do not inject the medication.
Figure 68. Inject the entire contents of the syringe intramuscularly.9. Withdraw the needle. Once the syringe has been withdrawn, immediately activate theLuproLoc safety device by pushing the arrow on the lock upward towards the needle tipwith the thumb or finger, as illustrated; until the needle cover of the safety device over theneedle is fully extended and a CLICK is heard or felt (see Figure 7).Figure 710. Dispose of the syringe according to local regulations/procedures.3 DOSAGE FORMS AND STRENGTHSLUPRON DEPOT 7.5 mg for 1-month administration, 22.5 mg for 3-month administration, 30mg for 4-month administration, and 45 mg for 6-month administration are each supplied as a kitwith prefilled dual chamber syringe.
4 CONTRAINDICATIONSLUPRON DEPOT is contraindicated in: HypersensitivityLUPRON DEPOT is contraindicated in individuals with known hypersensitivity toGnRH agonists or any of the excipients in LUPRON DEPOT. Reports of anaphylacticreactions to GnRH agonists have been reported in the medical literature. PregnancyLUPRON DEPOT may cause fetal harm when administered to a pregnant woman.Expected hormonal changes that occur with LUPRON DEPOT treatment increase therisk for pregnancy loss and fetal harm when administered to a pregnant woman.LUPRON DEPOT is contraindicated in women who are or may become pregnant. If thisdrug is used during pregnancy, or if the patient becomes pregnant while taking this drug,the patient should be apprised of the potential hazard to the fetus [see Use in SpecificPopulations (8.1)].5 WARNINGS AND PRECAUTIONS5.1 Tumor FlareInitially, LUPRON DEPOT, like other GnRH agonists, causes increases in serum levels oftestosterone to approximately 50% above baseline during the first weeks of treatment. Isolatedcases of ureteral obstruction and spinal cord compression have been observed, which maycontribute to paralysis with or without fatal complications. Transient worsening of symptomsmay develop. A small number of patients may experience a temporary increase in bone pain,which can be managed symptomatically.Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closelyobserved during the first few weeks of therapy.5.2 Hyperglycemia and DiabetesHyperglycemia and an increased risk of developing diabetes have been reported in men receivingGnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening ofglycemic control in patients with diabetes. Monitor blood glucose and/or glycosylatedhemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with currentpractice for treatment of hyperglycemia or diabetes.
5.3 Cardiovascular DiseasesIncreased risk of developing myocardial infarction, sudden cardiac death and stroke has beenreported in association with use of GnRH agonists in men. The risk appears low based on thereported odds ratios, and should be evaluated carefully along with cardiovascular risk factorswhen determining a treatment for patients with prostate cancer. Patients receiving a GnRHagonist should be monitored for symptoms and signs suggestive of development ofcardiovascular disease and be managed according to current clinical practice.5.4 Effect on QT/QTc IntervalAndrogen deprivation therapy may prolong the QT/QTc interval. Providers should considerwhether the benefits of androgen deprivation therapy outweigh the potential risks in patients withcongenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and inpatients taking drugs known to prolong the QT interval. Electrolyte abnormalities should becorrected. Consider periodic monitoring of electrocardiograms and electrolytes.5.5 ConvulsionsPostmarketing reports of convulsions have been observed in patients on leuprolide acetatetherapy. These included patients with a history of seizures, epilepsy, cerebrovascular disorders,central nervous system anomalies or tumors, and in patients on concomitant medications thathave been associated with convulsions such as bupropion and SSRIs. Convulsions have alsobeen reported in patients in the absence of any of the conditions mentioned above. Patientsreceiving a GnRH agonist who experience convulsion should be managed according to currentclinical practice.5.6 Laboratory TestsMonitor serum levels of testosterone following injection of LUPRON DEPOT 7.5 mg for 1month administration, 22.5 mg for 3-month administration, 30 mg for 4-month administration, or45 mg for 6-month administration. In the majority of patients, testosterone levels increasedabove baseline, and then declined thereafter to castrate levels ( 50 ng/dL) within four weeks.[see Clinical Studies (14) and Adverse Reactions (6)].6 ADVERSE REACTIONSBecause clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared to rates in the clinical trialsof another drug and may not reflect the rates observed in practice.
6.1 LUPRON DEPOT 7.5 mg for 1-Month AdministrationIn 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.Potential exacerbations of signs and symptoms during the first few weeks of treatment is aconcern in patients with vertebral metastases and/or urinary obstruction or hematuria which, ifaggravated, may lead to neurological problems such as temporary weakness and/or paresthesia ofthe lower limbs or worsening of urinary symptoms [see Warnings and Precautions (5.1)].In a clinical trial of LUPRON DEPOT 7.5 mg for 1-month administration, the following adversereactions were reported in 5% or more of the patients during the initial 24-week treatment period.Table 2. Adverse Reactions Reported in 5% of PatientsLUPRON DEPOT 7.5 mg for 1-Month Administration (N 56)Body As A WholeGeneral painInfectionCardiovascular SystemHot flashes/sweats*Digestive SystemGI disordersMetabolic and Nutritional DisordersEdemaNervous SystemLibido decreased*Respiratory SystemRespiratory disorderUrogenital SystemUrinary disorderImpotence*Testicular atrophy** Due to the expected physiologic effect of decreased testosterone .4)6(10.7)733(12.5)(5.4)(5.4)In this same study, the following adverse reactions were reported in less than 5% of the patientson LUPRON DEPOT 7.5 mg for 1-month administration.Body As A Whole - Asthenia, Cellulitis, Fever, Headache, Injection site reaction, NeoplasmCardiovascular System - Angina, Congestive heart failureDigestive System - Anorexia, Dysphagia, Eructation, Peptic ulcer
Hemic and Lymphatic System - EcchymosisMusculoskeletal System - MyalgiaNervous System - Agitation, Insomnia/sleep disorders, Neuromuscular disordersRespiratory System - Emphysema, Hemoptysis, Lung edema, Sputum increasedSkin and Appendages - Hair disorder, Skin reactionUrogenital System - Balanitis, Breast enlargement, Urinary tract infectionLaboratory AbnormalitiesAbnormalities of certain parameters were observed, but their relationship to drug treatment aredifficult to assess in this population. The following were recorded in 5% of patients at finalvisit: Decreased albumin, decreased hemoglobin/hematocrit, decreased prostatic acidphosphatase, decreased total protein, decreased urine specific gravity, hyperglycemia,hyperuricemia, increased BUN, increased creatinine, increased liver function tests (AST, LDH),increased phosphorus, increased platelets, increased prostatic acid phosphatase, increased totalcholesterol, increased urine specific gravity, leukopenia.6.2 LUPRON DEPOT 22.5 mg for 3-Month AdministrationIn two clinical trials of LUPRON DEPOT 22.5 mg for 3-month administration, the followingadverse reactions were reported to have a possible or probable relationship to drug as ascribed bythe treating physician in 5% or more of the patients receiving the drug. Often, causality isdifficult to assess in patients with metastatic prostate cancer. Reactions considered not drugrelated are excluded.Table 3. Adverse Reactions Reported in 5% of PatientsLUPRON DEPOT 22.5 mg for 3-Month AdministrationBody System/ReactionBody As A WholeAstheniaGeneral PainHeadacheInjection Site ReactionCardiovascular SystemHot flashes/SweatsDigestive SystemGI DisordersMusculoskeletal SystemN 94(%)725613(7.4)(26.6)(6.4)(13.8)55(58.5)15(16.0)
Joint DisordersCentral/Peripheral Nervous SystemDizziness/
1 INDICATIONS AND USAGE LUPRON DEPOT 7.5 mg for 1-month administration, 22.5 mg for 3-month administration, 30 mg for 4-month administration, and 45 mg for 6-month administration (leuprolide acetate) are
Aug 03, 2021 · Lupron Depot 3-Month 22.5 mg 1 injection 84 days Lupron Depot 4-Month 30 mg 1 injection 112 days Lupron Depot 6-Month 45 mg 1 injection 168 days Lupron Depot-Ped 1-month 7.5 mg 1 injection 28 days . Billing Code/Availability Information Drug Name Strength HCPCS* NDC Lupron Depot 1-Month 3.75 mg J1950 00074-3641-xxFile Size: 230KB
May 01, 2018 · Lupron Depot is administered intramuscularly (IM), Eligard is administered subcutaneously (SQ) VI. Billing Code/Availability Information Drug Name Strength HCPCS* NDC Lupron Depot 1-Month 3.75 mg J1950 00074-3641-xx Lupron Depot 1-Month 7.5 mg J9217 00074-3642-xx Lupron Depot 3-Month 11.25 mg J1950 00074-3663-xx
Sep 01, 2021 · J9155 Firmagon Degarelix J1572 Flebogamma Intravenous Immune Globulin Y J9307 Folotyn Pralatrexate Q5108 Fulphila Pegfilgrastim-jmdb . J1950 Lupron Depot Leuprolide acetate (for depot suspension) Y J1950 Lupron Depot Ped Leuprolide acetate (for depot suspension) Y A9513 Lutathera lutetium Lu 177 dotatate
Firmagon (degarelix) Lupaneta Pack (leuprolide acetate injection & norethindrone acetate tablets) Lupron Depot (leuprolide acetate) . The prescribing information for Lupron Depot and Zoladex state that the duration of initial t
Use of norethindrone acetate in combination with LUPRON DEPOT 11.25 mg is referred to as add-back therapy, and is intended to reduce the loss of bone mineral density (BMD) and to reduce vasomotor symptoms associated with use of LUPRON DEPOT 11.25 mg. Decide . between use of LUPRON DEPOT 11.25.mg alone or LUPRON DEPOT 11.25.mg plusFile Size: 630KB
water for injection, USP, and glacial acetic acid, USP to control pH. During the manufacture of LUPRON DEPOT–3 Month 11.25 mg, acetic acid is lost, leaving the peptide. CLINICAL PHARMACOLOGY . Leuprolide acetate is a long-act
Item Variable name Description Index Date index_date The date patients received degarelix (Firmagon) or leuprolide (Lupron depot) Index Medication index_med Patient’s first prescription of degarelix (Firmagon) or leuprolide (Lupron depot) Baseline Period baseline Any time before and including the index date used to establish a patient’s medical history
Quantum Field Theories: An introduction The string theory is a special case of a quantum field theory (QFT). Any QFT deals with smooth maps of Riemannian manifolds, the dimension of is the dimension of the theory. We also have an action function defined on the set Map of smooth maps. A QFT studies integrals Map ! #" % '&)( * &-, (1.1) Here ( * &-, stands for some measure on the space of .
