How to Acquire AVEED for Your Patients TM This guide provides helpful how-to information about: • Becoming an AVEED™ prescriber • Ordering AVEED • Locating billing and coding information for your AVEED order • Navigating reimbursement and insurance • Providing savings to your AVEED patients INDICATION AND IMPORTANT SAFETY INFORMATION WARNING: SERIOUS PULMONARY OIL MICROEMBOLISM (POME) REACTIONS AND ANAPHYLAXIS •S erious POME reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope; and episodes of anaphylaxis, including life-threatening reactions, have been reported to occur during or immediately after the administration of testosterone undecanoate injection. These reactions can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. •F ollowing each injection of AVEED™ (testosterone undecanoate) injection, for intramuscular use CIII, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis. •B ecause of the risks of serious POME reactions and anaphylaxis, AVEED is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the AVEED REMS Program. INDICATIONS AND USAGE AVEEDTM is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. •P rimary hypogonadism (congenital or acquired): testicular failure due to cryptochordism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. •H ypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range. AVEED should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis. Limitations of use: • Safety and efficacy of AVEED in males less than 18 years old have not been established. Please see full Important Safety Information on pages 9-11 and accompanying full Prescribing Information, including Boxed Warning. AVEED Provider Enrollment Program TM Why Is Enrollment Required? The AVEED™ Provider Enrollment Program is required by the FDA. The program is designed to train all healthcare professionals who prescribe and/or administer AVEED about the risk of immediate post-injection reactions, specifically pulmonary oil microembolism (POME) and anaphylaxis. Among 3,556 patients in worldwide clinical trials1: • 9 POME events occurred in 8 patients • 2 events of anaphylaxis occurred Program Requirements Healthcare settings must be certified in the AVEED REMS* Program to be able to order AVEED. One representative needs to enroll per healthcare setting (the “Authorized Representative”). Prescribing Healthcare Providers must be certified in the AVEED REMS Program to be able to prescribe AVEED. Non-prescribing Healthcare Providers who will administer AVEED to patients must be trained on the AVEED REMS Education Program for Healthcare Providers. *Risk Evaluation and Mitigation Strategy For further information and to enroll in the AVEED™ Provider Enrollment Program, please visit the AVEED Provider Enrollment Program website at AveedREMS.com or call 1-855-755-0494 to request materials. IMPORTANT SAFETY INFORMATION •A VEED is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate and women who are or may become pregnant, or who are breastfeeding. AVEED may cause serious adverse reactions in nursing infants. Testosterone can cause fetal harm when administered to a pregnant woman. Exposure of a fetus or nursing infant to androgens may result in varying degrees of virilization. •A VEED is contraindicated in men with known hypersensitivity to AVEED or any of its ingredients (testosterone undecanoate, refined castor oil, benzyl benzoate). •S erious POME reactions, involving cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular testosterone undecanoate 1000 mg (4 mL). The majority of these events lasted a few minutes and resolved; however, some lasted up to several hours and some required emergency care and/or hospitalization. To minimize the risk of intravascular injection of AVEED, care should be taken to inject the preparation deeply into the gluteal muscle, being sure to follow the recommended procedure for intramuscular administration. • I n addition to serious POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular testosterone undecanoate. 2 Steps for Healthcare Setting Enrollment 1 Get started at AveedREMS.com 2 Review Training Materials 3 Complete Enrollment Process 4 Implementation Designate an Authorized Representative. This may be a prescribing or non-prescribing HCP, practice manager, or any responsible individual in a healthcare setting. Review the AVEED REMS Education Program for Healthcare Settings, including Prescribing Information. Complete and sign the Healthcare Setting Enrollment Form. This enrollment must be renewed every 2 years. Implement the necessary staff training and processes to comply with the AVEED™ REMS Program requirements. Steps for Healthcare Provider Enrollment 1 Ensure that Your Healthcare Setting Is Enrolled 2 Get Started at AveedREMS.com 3 Review Training Materials 4 Complete Knowledge Assessment and Submit Enrollment Form Healthcare Providers can begin the process to becoming certified to prescribe AVEED™ by creating an account with the AVEED Provider Enrollment Program at AveedREMS.com. After creating an account, Healthcare Providers will be able to access and review the AVEED REMS Education Program for Healthcare Providers, including Prescribing Information. Successfully complete the 10-question Knowledge Assessment, then sign and submit the one-time Healthcare Provider Enrollment Form to begin prescribing AVEED. IMPORTANT SAFETY INFORMATION (CONT) •B oth serious POME reactions and anaphylaxis can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. Patients with suspected hypersensitivity reactions to AVEED should not be re-treated with AVEED. •F ollowing each injection of AVEED, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions and anaphylaxis. •A VEED is available only through a restricted program called the AVEED REMS Program because of the risk of serious POME and anaphylaxis. Please see full Important Safety Information on pages 9-11 and accompanying full Prescribing Information, including Boxed Warning. 3 – Reimbursement Hotline A Helpful Resource for Navigating Insurance, Acquiring AVEED™, Reimbursment, and More myAVEED is your one-stop source for product support. With myAVEED, healthcare professionals call just one phone number for assistance with: • Contacting patient health plan to verify benefit coverage and eligibility • Ordering and processing Specialty Pharmacy prescriptions • Ordering AVEED™ for your patients • Managing prior authorizations • Reimbursement support • Determining eligibility and enrollment in the AVEED Patient Savings Program • Questions about coding AVEED on health plan claims Get Started With myAVEED • In order to access the support provided by myAVEED, please contact a hotline representative at 1-855-myAVEED (692-8333) • To initiate a benefits investigation or a prescription via Specialty Pharmacy, complete and fax a Benefits Investigation and Enrollment Form and a Patient Authorization Form to 1-877-488-6701 •T o determine patient eligibility for the AVEED Patient Savings Program, have the patient sign the Patient Savings portion of the Patient Authorization Form and fax it along with the Benefits Investigation and Enrollment Form FAX A BENEFITS INVESTIGATION AND ENROLLMENT FORM TO 1-877-488-6701 OR CALL FOR ASSISTANCE 1-855-myAVEED (692-8333) 8 am to 8 pm EST • Forms are available through your sales representative or by visiting AveedUSA.com/PrescriberResources IMPORTANT SAFETY INFORMATION (CONT) Notable requirements of the AVEED REMS Program include the following: •H ealthcare providers who prescribe AVEED must be certified with the REMS program before ordering or dispensing AVEED. •H ealthcare settings must be certified with the REMS Program and have healthcare providers who are certified before ordering or dispensing AVEED. Healthcare settings must have on-site access to equipment and personnel trained to manage serious POME and anaphylaxis. Further information is available at www.AveedREMS.com or call 1-855-755-0494. •P atients with Benign Prostatic Hyperplasia (BPH) treated with androgens are at an increased risk of worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at an increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens. • Increases in hematocrit, reflective of increases in red blood cell mass, may require discontinuation of testosterone. Check hematocrit prior to initiating testosterone treatment. It would be appropriate to re-evaluate the hematocrit 3 to 6 months after starting testosterone treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable level. An increase in red blood cell mass may increase the risk of thromboembolic events. 4 Ordering AVEED TM Choose Buy-and-Bill or Specialty Pharmacy Depending on your preferences, and your patient’s health plans, you may order AVEED via one of these two methods: 1 uy-and-Bill: Buy AVEED exclusively through one of the Specialty Distributors listed below and B bill it to the patient or patient’s health plan along with professional services. Collect copay/coinsurance from the patient. Buy-and-Bill Distributors 2 Besse Medical Cardinal Specialty 888-252-5585 Acute Care: 866-476-1340 Urology: 866-300-3838 www.besse.com specialtyonlinecardinalhealth.com McKesson Specialty Smith Medical Partners 855-477-9800 800-292-9653 https://mscs.mckesson.com www.smpspecialty.com Specialty Pharmacy: Getting started via Specialty Pharmacy is as easy as completing and faxing a Benefits Investigation and Enrollment Form to myAVEED at 1-877-488-6701. With the help of myAVEED, you can acquire AVEED exclusively through a Specialty Pharmacy Provider, which bills the patient or patient’s health plan directly, then delivers the medication after payment is received. In this scenario, you only bill for your professional services. The prescription will be sent to a certified healthcare setting, such as your office or hospital. To order via Specialty Pharmacy, fax a Benefits Investigation and Enrollment Form to 1-877-488-6701, or call 1-855-myAVEED (692-8333) IMPORTANT SAFETY INFORMATION (CONT) •D ue to lack of controlled evaluations in women and potential virilizing effects, AVEED is not indicated for use in women. •W ith large doses of exogenous androgens, including AVEED, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH, which could possibly lead to adverse effects on semen parameters including sperm count. •P rolonged use of high doses of orally active 17-alpha-alkyl androgens has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. AVEED is not known to produce these adverse effects. Patients should report signs and symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue AVEED while the cause is evaluated. •A ndrogens, including AVEED, may promote retention of sodium and water. Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required. •G ynecomastia may develop and may persist in patients being treated with androgens, including AVEED, for hypogonadism. Please see full Important Safety Information on pages 9-11 and accompanying full Prescribing Information, including Boxed Warning. 5 AVEED Patient Savings Program TM $0 Copay on Your Patient’s First 2 Injections …and No More Than $30 Copay for Each Additional Injection* Eligible patients pay $0 copay on their first 2 injections with the AVEED Patient Savings Program.* The program will pay up to a maximum reimbursement of $165 for each of their first 2 AVEED injections— PLUS, up to a maximum reimbursement of $135 for each injection thereafter. If their total out of pocket expense exceeds these amounts they are responsible for the additional amounts. Some restrictions apply.† Offer not valid for prescriptions that may be reimbursed under a federal or state healthcare program, including Medicare, Medicaid, or any other federal or state healthcare programs. AveedUSA.com IMPORTANT SAFETY INFORMATION (CONT) 6 • The treatment of hypogonadal men with testosterone products may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases. • Changes in serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy. • Androgens, including AVEED, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients. • Androgens, including AVEED, may decrease concentrations of thyroxine-binding globulin resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. • Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of anti-diabetic medication. • Changes in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy. Here’s how patients receive the rebate If you choose the Buy-and-Bill method: If your patient is insured, copay will need to be collected by your practice. Your patient can then submit a rebate form, along with their Explanation of Benefits and the bill indicating the amount the patient paid for AVEED, to have the rebate mailed to them. Rebate forms are available from your Sales Representative or through AveedUSA.com/PatientSavings. Eligible patients paying cash can also receive a rebate of up to $165. If you choose to order via Specialty Pharmacy with processing by myAVEED: Patients will automatically be evaluated for copay savings eligibility, and the savings will be applied through the order, reducing the cost, once the signed Patient Authorization Form has been submitted. To get started, please contact a hotline representative at 1-855-myAVEED (692-8333), or complete and fax a Benefits Investigation and Enrollment Form to 1-877-488-6701. Download forms at AveedUSA.com/PhysicianResources or contact your AVEED sales representative. *On the first 2 AVEED injections, maximum savings is $165 per use. On subsequent injections, patient pays the first $30 of copay. Program pays up to a maximum of $135 per use. Patient is responsible for any balance remaining, and for reporting receipt of this coupon benefit to any insurer, health plan, or other third party who pays for or reimburses any part of the prescription filled using the coupon, as may be required. Patient and prescriber agree not to seek reimbursement for all or any part of the benefit received by the patient through this offer. Terms and Conditions: Offer good only in the USA and void where prohibited or otherwise restricted by law. Offer is valid for patients with private insurance or paying cash. Offer not valid for prescriptions that may be reimbursed under a federal or state healthcare program, including Medicare, Medicaid, or any other federal or state healthcare programs, including any state medical pharmaceutical assistance programs. If there are any questions please call 1-800-381-2638. † Limitations apply, Endo Pharmaceuticals reserves the right to rescind, revoke, or amend this program without notice. Patient is responsible for reporting receipt of program rewards to any private insurer that pays for or reimburses any part of the prescriptions filled with this program. Offer expires on 3/1/2015. IMPORTANT SAFETY INFORMATION (CONT) • The concurrent use of testosterone with corticosteroids may result in increased fluid retention and requires careful monitoring, particularly in patients with cardiac, renal or hepatic disease. • There have not been sufficient numbers of geriatric patients in controlled clinical studies with AVEED to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. • AVEED contains testosterone undecanoate, a Scheduled III controlled substance in the Controlled Substances Act. • Anabolic steroids, such as testosterone, are abused. Please see full Important Safety Information on pages 9-11 and accompanying full Prescribing Information, including Boxed Warning. 7 AVEED Coding Information TM Commonly Used Codes for AVEED™ Product Code (HCPCS) J3490 Unclassified drugs Unclassified drugs product code can be used for AVEED until a specific AVEED code has been issued. National Drug Code (NDC) 67979-511-43 (10-digit) 67979-0511-43 (11-digit) AVEED 750 mg/3 mL (250 mg/mL) The 11-digit billing format is an electronic transaction standard required by many health plans that require NDC codes for billing. Check with the health plan for the requirements specific to your patient. Diagnosis Code (ICD-9-CM) 257.2 Testicular dysfunction (other testicular hypofunction) – includes testicular hypogonadism CPT Code (Intramuscular Injection of AVEED) 96372 8 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular INDICATION AND IMPORTANT SAFETY INFORMATION WARNING: SERIOUS PULMONARY OIL MICROEMBOLISM (POME) REACTIONS AND ANAPHYLAXIS •S erious POME reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope; and episodes of anaphylaxis, including life-threatening reactions, have been reported to occur during or immediately after the administration of testosterone undecanoate injection. These reactions can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. •F ollowing each injection of AVEED™ (testosterone undecanoate) injection, for intramuscular use CIII, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis. •B ecause of the risks of serious POME reactions and anaphylaxis, AVEED is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the AVEED REMS Program. INDICATIONS AND USAGE AVEEDTM is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. •P rimary hypogonadism (congenital or acquired): testicular failure due to cryptochordism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. •H ypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range. AVEED should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis. Limitations of use: •S afety and efficacy of AVEED in males less than 18 years old have not been established. IMPORTANT SAFETY INFORMATION •A VEED is contraindicated in men with carcinoma of the breast or known or suspected carcinoma of the prostate and women who are or may become pregnant, or who are breastfeeding. AVEED may cause serious adverse reactions in nursing infants. Testosterone can cause fetal harm when administered to a pregnant woman. Exposure of a fetus or nursing infant to androgens may result in varying degrees of virilization. •A VEED is contraindicated in men with known hypersensitivity to AVEED or any of its ingredients (testosterone undecanoate, refined castor oil, benzyl benzoate). •S erious POME reactions, involving cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular testosterone undecanoate 1000 mg (4 mL). The majority of these events lasted a few minutes and resolved; however, some lasted up to several hours and some required emergency care and/or hospitalization. To minimize the risk of intravascular injection of AVEED, care should be taken to inject the preparation deeply into the gluteal muscle, being sure to follow the recommended procedure for intramuscular administration. • I n addition to serious POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular testosterone undecanoate. •B oth serious POME reactions and anaphylaxis can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. Patients with suspected hypersensitivity reactions to AVEED should not be re-treated with AVEED. •F ollowing each injection of AVEED, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions and anaphylaxis. •A VEED is available only through a restricted program called the AVEED REMS Program because of the risk of serious POME and anaphylaxis. Notable requirements of the AVEED REMS Program include the following: •H ealthcare providers who prescribe AVEED must be certified with the REMS program before ordering or dispensing AVEED. •H ealthcare settings must be certified with the REMS Program and have healthcare providers who Please see additional full Important Safety Information on pages 10-11 and accompanying full Prescribing Information, including Boxed Warning. 9 IMPORTANT SAFETY INFORMATION (CONT) are certified before ordering or dispensing AVEED. Healthcare settings must have on-site access to equipment and personnel trained to manage serious POME and anaphylaxis. Further information is available at www.AveedREMS.com or call 1-855-755-0494. •P atients with Benign Prostatic Hyperplasia (BPH) treated with androgens are at an increased risk of worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at an increased risk for prostate cancer. Evaluate patients for prostate cancer prior to initiating and during treatment with androgens. • Increases in hematocrit, reflective of increases in red blood cell mass, may require discontinuation of testosterone. Check hematocrit prior to initiating testosterone treatment. It would be appropriate to re-evaluate the hematocrit 3 to 6 months after starting testosterone treatment, and then annually. If hematocrit becomes elevated, stop therapy until hematocrit decreases to an acceptable level. An increase in red blood cell mass may increase the risk of thromboembolic events. •D ue to lack of controlled evaluations in women and potential virilizing effects, AVEED is not indicated for use in women. •W ith large doses of exogenous androgens, including AVEED, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH, which could possibly lead to adverse effects on semen parameters including sperm count. •P rolonged use of high doses of orally active 17-alphaalkyl androgens has been associated with serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms, cholestatic hepatitis, and jaundice). Peliosis hepatis can be a life-threatening or fatal complication. Long-term therapy with intramuscular testosterone enanthate has produced multiple hepatic adenomas. AVEED is not known to produce these adverse effects. Patients should report signs and symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue AVEED while the cause is evaluated. •A ndrogens, including AVEED, may promote retention of sodium and water. Edema with or without congestive heart failure may be a serious complication in patients with preexisting cardiac, renal, or hepatic disease. In addition to discontinuation of the drug, diuretic therapy may be required. •G ynecomastia may develop and may persist in patients being treated with androgens, including AVEED, for hypogonadism. 10 •T he treatment of hypogonadal men with testosterone products may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung diseases. •C hanges in serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy. •A ndrogens, including AVEED, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Regular monitoring of serum calcium concentrations is recommended in these patients. •A ndrogens, including AVEED, may decrease concentrations of thyroxine-binding globulin resulting in decreased total T4 serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone concentrations remain unchanged, however, and there is no clinical evidence of thyroid dysfunction. •C hanges in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may necessitate a decrease in the dose of anti-diabetic medication. •C hanges in anticoagulant activity may be seen with androgens, therefore more frequent monitoring of international normalized ratio (INR) and prothrombin time are recommended in patients taking warfarin, especially at the initiation and termination of androgen therapy. •T he concurrent use of testosterone with corticosteroids may result in increased fluid retention and requires careful monitoring, particularly in patients with cardiac, renal or hepatic disease. •T here have not been sufficient numbers of geriatric patients in controlled clinical studies with AVEED to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. •A VEED contains testosterone undecanoate, a Scheduled III controlled substance in the Controlled Substances Act. •A nabolic steroids, such as testosterone, are abused. •T here have been no reports of overdosage in the AVEED clinical trials. There is one report of acute overdosage with use of an approved injectable testosterone product. Treatment of overdosage would consist of discontinuation of AVEED with appropriate symptomatic and supportive care. •A VEED was evaluated in an 84-week clinical study using a dose regimen of 750 mg (3 mL) at initiation, at 4 weeks, and every 10 weeks thereafter in 153 hypogonadal men. The most commonly reported adverse reactions (>2%) were: acne (5.2%), injection site pain (4.6%), prostate specific antigen increased (4.6%), hypogonadism (2.6%) and estradiol increased (2.6%). IMPORTANT SAFETY INFORMATION (CONT) •P ostmarketing Experience The following adverse events have been identified during post-approval use of AVEED. Because the reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or to establish a causal relationship to drug exposure. Serious pulmonary oil microembolism (POME) reactions, involving cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope, have been reported to occur during or immediately after the injection of intramuscular testosterone undecanoate 1000 mg (4 mL) in postapproval use outside the United States. The majority of these events lasted a few minutes and resolved with supportive measures; however, some lasted up to several hours and some required emergency care and/ or hospitalization. In addition to serious POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported to occur following the injection of intramuscular testosterone undecanoate in postapproval use outside of the United States. Both serious POME reactions and anaphylaxis have been reported to occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. Other Events The following treatment emergent adverse events or adverse reactions have been identified during postmarketing clinical trials and during post-approval use outside the United States of intramuscular testosterone undecanoate. In most cases, the dose being used was 1000 mg. Blood and Lymphatic System Disorders: polycythemia, thrombocytopenia Cardiac Disorders: angina pectoris, cardiac arrest, cardiac failure, coronary artery disease, coronary artery occlusion, myocardial infarction, tachycardia Ear and Labyrinth Disorders: sudden hearing loss, tinnitus Endocrine Disorders: hyperparathyroidism, hypoglycemia Gastrointestinal Disorders: abdominal pain upper, diarrhea, vomiting General Disorders and Administrative Site Conditions: chest pain, edema peripheral, injection site discomfort, injection site hematoma, injection site irritation, injection site pain, injection site reaction, malaise, paresthesia, procedural pain Immune System Disorders: anaphylactic reaction, anaphylactic shock, asthma, dermatitis allergic, hypersensitivity, leukocytoclastic vasculitis Infections and Infestations: injection site abscess, prostate infection Investigations: alanine aminotransferase increased, aspartate aminotransferase increased, blood bilirubin increased, blood glucose increased, blood pressure increased, blood prolactin increased, blood testosterone decreased, blood testosterone increased, blood triglycerides increased, gammaglutamyltransferase increased, hematocrit increased, intraocular pressure increased, liver function test abnormal, prostate examination abnormal, prostatic specific antigen increased, transaminases increased Metabolism and Nutrition Disorders: diabetes mellitus, fluid retention, hyperlipidemia, hypertriglyceridemia Musculoskeletal and Connective Tissue Disorders: musculoskeletal chest pain, musculoskeletal pain, myalgia, osteopenia, osteoporosis, systemic lupus erythematosus Neoplasms Benign, Malignant and Unspecified (including cysts and polyps): prostate cancer, prostatic intraepithelial neoplasia Nervous System Disorders: cerebrovascular insufficiency, reversible ischemic neurological deficiency, transient ischemic attack Psychiatric Disorders: aggression, anxiety, depression, insomnia, irritability, Korsakoff’s psychosis nonalcoholic, male orgasmic disorder, nervousness, restlessness, sleep disorder Renal and Urinary Disorders: calculus urinary, dysuria, hematuria, nephrolithiasis, pollakiuria, renal colic, renal pain, urinary tract disorder Reproductive System and Breast Disorders: benign prostatic hyperplasia, breast induration, breast pain, erectile dysfunction, gynecomastia, libido decreased, libido increased, prostate induration, prostatitis, spermatocele, testicular pain Respiratory, Thoracic and Mediastinal Disorders: asthma, chronic obstructive pulmonary disease, cough, dysphonia, dyspnea, hyperventilation, obstructive airway disorder, pharyngeal edema, pharyngolaryngeal pain, pulmonary microemboli, pulmonary embolism, respiratory distress, rhinitis, sleep apnea syndrome, snoring Skin and Subcutaneous Tissue Disorders: acne, alopecia, angioedema, angioneurotic edema, dermatitis allergic, erythema, hyperhidrosis, pruritus, rash Vascular Disorders: cerebral infarction, cerebrovascular accident, circulatory collapse, deep venous thrombosis, hot flush, hypertension, syncope, thromboembolism, thrombosis, venous insufficiency Please see accompanying full Prescribing Information, including Boxed Warning. 11 AveedUSA.com To learn how you can become a certified AVEED™ prescriber, call 1-855-755-0494, or go to AveedREMS.com. For questions about acquiring AVEED, billing and reimbursement related information, or how to provide savings for your patients, call 1-855-myAVEED (692-8333), anytime between 8 am and 8 pm EST. To learn more and to download forms, visit AveedUSA.com. INDICATION AND IMPORTANT SAFETY INFORMATION WARNING: SERIOUS PULMONARY OIL MICROEMBOLISM (POME) REACTIONS AND ANAPHYLAXIS •S erious POME reactions, involving urge to cough, dyspnea, throat tightening, chest pain, dizziness, and syncope; and episodes of anaphylaxis, including life-threatening reactions, have been reported to occur during or immediately after the administration of testosterone undecanoate injection. These reactions can occur after any injection of testosterone undecanoate during the course of therapy, including after the first dose. •F ollowing each injection of AVEED™ (testosterone undecanoate) injection, for intramuscular use CIII, observe patients in the healthcare setting for 30 minutes in order to provide appropriate medical treatment in the event of serious POME reactions or anaphylaxis. •B ecause of the risks of serious POME reactions and anaphylaxis, AVEED is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the AVEED REMS Program. INDICATIONS AND USAGE AVEEDTM is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. •P rimary hypogonadism (congenital or acquired): testicular failure due to cryptochordism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter’s syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (follicle-stimulating hormone [FSH], luteinizing hormone [LH]) above the normal range. •H ypogonadotropic hypogonadism (congenital or acquired): idiopathic gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency or pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low testosterone serum concentrations but have gonadotropins in the normal or low range. AVEED should only be used in patients who require testosterone replacement therapy and in whom the benefits of the product outweigh the serious risks of pulmonary oil microembolism and anaphylaxis. Limitations of use: • Safety and efficacy of AVEED in males less than 18 years old have not been established. Please see full Important Safety Information on pages 9-11 and accompanying full Prescribing Information, including Boxed Warning. REFERENCE: 1. AVEED™ (Prescribing Information). Malvern, PA: Endo Pharmaceuticals Inc; 2014. Rx Only AVEED™ is a trademark of Endo Pharmaceuticals Inc. © 2014 Endo Pharmaceuticals Inc. All Rights Reserved. Malvern, PA 19355 AV-03047a/March 2014 www.AveedUSA.com 1-800-462-ENDO (3636)