DailyMed Label: Aveed

DailyMed Label: Aveed

2021

DailyMed Prescription

Aveed

testosterone undecanoate

ENDO USA, Inc.

NDC: 67979-511

NDC: 67979-511

NDC: 67979-511

NDC: 67979-511

NDC: 67979-511

NDC: 67979-511

NDC: 67979-511

AVEED (testosterone undecanoate) injection contains testosterone undecanoate (17β-undecanoyloxy-4-androsten-3-one) which is an ester of the androgen, testosterone. Testosterone is formed by cleavage of the ester side chain of testosterone undecanoate.  Testosterone undecanoate is a white to off-white crystalline substance. The empirical formula of testosterone undecanoate is C 30 H 48 O 3 and a molecular weight of 456.7.  The structural formula is:                                                             Figure 2:           Testosterone Undecanoate                                                                                                           C 30 H 48 O 3                             MW:  456.7 AVEED is a clear, yellowish, sterile oily solution containing testosterone undecanoate, a testosterone ester, for intramuscular injection. Each single use vial contains 3 mL of 250 mg/mL testosterone undecanoate solution in a mixture of 1500 mg of benzyl benzoate and 885 mg of refined castor oil. Figure2

AVEED is indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone. Primary hypogonadism (congenital or acquired): testicular failure due to cryptorchidism, 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. Hypogonadotropic hypogonadism (congenital or acquired): 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 POME and anaphylaxis. Limitations of Use Safety and efficacy of AVEED in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established. Safety and efficacy of AVEED in males less than 18 years old have not been established [see Use in Specific Populations ( 8.4 )]. Aveed (testosterone undecanoate) injection is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone: Primary hypogonadism (congenital or acquired) ( 1 ) Hypogonadotropic hypogonadism (congenital or acquired) ( 1 ) 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 ( 1 ). Limitations of Use Safety and efficacy of Aveed in men with “age-related hypogonadism” have not been established ( 1 ).  Safety and efficacy of Aveed in males less than 18 years old have not been established ( 1 , 8.4 ).

Prior to initiating AVEED, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least 2 separate days and that these serum testosterone concentrations are below the normal range. Prior to initiating Aveed, confirm the diagnosis of hypogonadism by ensuring that serum testosterone has been measured in the morning on at least two separate days and that these concentrations are below the normal range ( 2 ). For intramuscular use only ( 2.1 ). Three (3) mL (750 mg) is to be injected intramuscularly at initiation, at 4 weeks, and every 10 weeks thereafter ( 2.1 ). Following 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 or anaphylaxis ( 2.3 ). Inject Aveed deeply into the gluteal muscle following the usual precautions for intramuscular administration of oily solutions ( 2.3 ). AVEED is for intramuscular use only.  Dosage titration is not necessary. Inject AVEED deeply into the gluteal muscle following the usual precautions for intramuscular administration; care must be taken to avoid intravascular injection [see Dosage and Administration ( 2.3 )] . Intravascular injection of AVEED may lead to POME [see Warnings and Precautions ( 5.1 )]. The recommended dose of AVEED is 3 mL (750 mg) injected intramuscularly, followed by 3 mL (750 mg) injected after 4 weeks, then 3 mL (750 mg) injected every 10 weeks thereafter. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Carefully remove the gray plastic cap from the top of the vial by lifting it up from the edges with your fingers or by pushing the bottom edge of the cap upward using the top of your thumb.  Remove only the gray plastic cap while leaving the aluminum metal ring and crimp seal around the gray rubber stopper in place. To facilitate the removal of medication from the vial, attach an 18-gauge needle and draw 3 mL of air into the syringe. Hold the needle at a 45° angle to the stopper with the bevel in the up orientation. Inject through the gray rubber stopper into the vial to create positive pressure within the vial chamber. Withdraw 3 mL (750 mg) of AVEED solution from the vial.  Expel excess air bubbles from the syringe.  Replace the syringe needle used to draw up the solution from the vial with a new intramuscular needle and inject.  Discard any unused portion in the vial. The site for injection for AVEED is the gluteus medius muscle site located in the upper outer quadrant of the buttock.  Care must be taken to avoid the needle hitting the superior gluteal arteries and sciatic nerve.  Between consecutive injections, alternate the injection site between left and right buttock.                                                             Figure 1:  Identifying the Injection Site                                        Following antiseptic skin preparation, enter the muscle and maintain the syringe at a 90° angle with the needle in its deeply imbedded position.  Grasp the barrel of the syringe firmly with one hand.  With the other hand, pull back on the plunger and aspirate for several seconds to ensure that no blood appears.  If any blood is drawn into the syringe, immediately withdraw and discard the syringe and prepare another dose.    If no blood is aspirated, reinforce the current needle position to avoid any movement of the needle and slowly (over 60 to 90 seconds) depress the plunger carefully and at a constant rate, until all the medication has been delivered.  Be sure to depress the plunger completely with sufficient controlled force.  Withdraw the needle.  Immediately upon removal of the needle from the muscle, apply gentle pressure with a sterile pad to the injection site.  If there is bleeding at the site of injection, apply a bandage. Following 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 or anaphylaxis [see Warnings and Precautions ( 5.1 )]. Figure1

750 mg/3 mL (250 mg/mL) testosterone undecanoate sterile injectable solution is provided in an amber glass, single use vial with silver-colored crimp seal and gray plastic cap. 750 mg/3 mL (250 mg/mL) testosterone undecanoate sterile injectable solution is provided in an amber glass, single use vial with silver-colored crimp seal and gray plastic cap ( 3 ).

AVEED should not be used in any of the following patients: Men with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions ( 5.3 )]. Women who are pregnant. Testosterone can cause virilization of the female fetus when administered to a pregnant woman [see Use in Specific Populations ( 8.1 , 8.2 )] .  Men with known hypersensitivity to AVEED or any of its ingredients (testosterone undecanoate, refined castor oil, benzyl benzoate). Men with carcinoma of the breast or known or suspected carcinoma of the prostate ( 4 , 5.3 ). Women who are pregnant. Testosterone may cause fetal harm ( 4 , 5.8 , 8.1 , 8.2 ). Known hypersensitivity to Aveed or its ingredients (testosterone undecanoate, refined castor oil, benzyl benzoate) ( 4 ).

Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH ( 5.3 ). Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Evaluate patients with signs or symptoms consistent with DVT or PE ( 5.5 ). Some postmarketing studies have shown an increased risk of myocardial infarction and stroke associated with use of testosterone replacement therapy ( 5.6 ). Exogenous administration of androgens may lead to azoospermia ( 5.9 ). Edema with or without congestive heart failure may be a complication in patients with preexisting cardiac, renal, or hepatic disease ( 5.11 ). Sleep apnea may occur in those with risk factors ( 5.13 ). Monitor prostatic specific antigen (PSA), hemoglobin, hematocrit, and lipid concentrations periodically ( 5.3 , 5.4 , 5.14 ). Serious 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 with supportive measures; 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 [see Dosage and Administration ( 2.2 , 2.3 ) and Adverse Reactions ( 6.2 )] . 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.  Both 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.   Following 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. AVEED 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: Healthcare providers who prescribe AVEED must be certified with the REMS Program before ordering or dispensing AVEED. Healthcare 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. Patients with 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 [see Contraindications ( 4 )] . 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. There have been postmarketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone products, such as AVEED. Evaluate patients who report symptoms of pain, edema, warmth and erythema in the lower extremity for DVT and those who present with acute shortness of breath for PE. If a venous thromboembolic event is suspected, discontinue treatment with AVEED and initiate appropriate workup and management. Long-term clinical safety trials have not been conducted to assess the cardiovascular outcomes of testosterone replacement therapy in men. To date, epidemiologic studies and randomized controlled trials have been inconclusive for determining the risk of major adverse cardiovascular events (MACE), such as non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death, with the use of testosterone compared to non-use. Some studies, but not all, have reported an increased risk of MACE in association with use of testosterone replacement therapy in men. Patients should be informed of this possible risk when deciding whether to use or to continue to use AVEED. Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids.  Anabolic androgenic steroid abuse can lead to serious cardiovascular and psychiatric adverse reactions [see Drug Abuse and Dependence ( 9 )]. If testosterone abuse is suspected, check serum testosterone concentrations to ensure they are within therapeutic range. However, testosterone levels may be in the normal or subnormal range in men abusing synthetic testosterone derivatives. Counsel patients concerning the serious adverse reactions associated with abuse of testosterone and anabolic androgenic steroids. Conversely, consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events. Due to lack of controlled evaluations in women and potential virilizing effects, AVEED is not indicated for use in women [see Contraindications ( 4 ) and Use in Specific Populations ( 8.1 , 8.2 )] . With 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. Prolonged use of high doses of orally active 17-alpha-alkyl androgens (eg, methyltestosterone) 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, which elevates blood levels for prolonged periods, has produced multiple hepatic adenomas.  AVEED is not known to produce these adverse effects. Nonetheless, patients should be instructed to report any signs or symptoms of hepatic dysfunction (eg, jaundice).  If these occur, promptly discontinue AVEED while the cause is evaluated. Androgens, 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. Gynecomastia occasionally develops and occasionally persists in patients being treated for hypogonadism [see Adverse Reactions ( 6.1 )] . 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.

The most commonly reported adverse reactions (≥2%) are acne, injection site pain, prostatic specific antigen (PSA) increased, estradiol increased, hypogonadism, fatigue, irritability, hemoglobin increased, insomnia, and mood swings (

Androgens may decrease blood glucose, and therefore may decrease insulin requirements in diabetic patients ( 7.1 ). Changes in anticoagulant activity may be seen with androgens.  More frequent monitoring of international normalized ratio (INR) and prothrombin time is recommended in patients taking warfarin ( 7.2 ). Use of testosterone with corticosteroids may result in increased fluid retention.  Use with caution, particularly in patients with cardiac, renal, or hepatic disease ( 7.3 ). 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. 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.

Geriatric Patients: There are insufficient long-term safety data to assess the potential risks of cardiovascular disease and prostate cancer ( 8.5 ). Risk Summary AVEED is contraindicated in pregnant women. Testosterone is teratogenic and may cause fetal harm based on data from animal studies and its mechanism of action [see Contraindications ( 4 ) and Clinical Pharmacology ( 12.1 )] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal development studies, exposure to testosterone in utero resulted in hormonal and behavioral changes in offspring and structural impairments of reproductive tissues in female and male offspring. These studies did not meet current standards for nonclinical development toxicity studies. Data Animal Data In developmental studies conducted in rats, rabbits, pigs, sheep and rhesus monkeys, pregnant animals received intramuscular injection of testosterone during the period of organogenesis. Testosterone treatment at doses that were comparable to those used for testosterone replacement therapy resulted in structural impairments in both female and male offspring. Structural impairments observed in females included increased anogenital distance, phallus development, empty scrotum, no external vagina, intrauterine growth retardation, reduced ovarian reserve, and increased ovarian follicular recruitment. Structural impairments seen in male offspring included increased testicular weight, larger seminal tubular lumen diameter, and higher frequency of occluded tubule lumen. Increased pituitary weight was seen in both sexes. Testosterone exposure in utero also resulted in hormonal and behavioral changes in offspring. Hypertension was observed in pregnant female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy. Risk Summary AVEED is not indicated for use in females. Infertility During treatment with large doses of exogenous androgens, including AVEED, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see Warnings and Precautions ( 5.9 )] , possibly leading to adverse effects on semen parameters including sperm count. Reduced fertility is observed in some men taking testosterone replacement therapy. Testicular atrophy, subfertility, and infertility have also been reported in men who abuse anabolic androgenic steroids [see Drug Abuse and Dependence ( 9.2 )] . With either type of use, the impact on fertility may be irreversible. Safety and effectiveness of AVEED in pediatric patients less than 18 years old have not been established.  Improper use may result in acceleration of bone age and premature closure of epiphyses. 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. Of the 153 patients enrolled in the pivotal clinical study utilizing AVEED, 26 (17.0%) were over 65 years of age. Additionally, there are insufficient long-term safety data in geriatric patients to assess the potentially increased risk of cardiovascular disease and prostate cancer . Geriatric patients treated with androgens may also be at risk for worsening of signs and symptoms of BPH [see Warnings and Precautions ( 5.3 )] . No studies were conducted in patients with renal impairment. No studies were conducted in patients with hepatic impairment.

AVEED, NDC 67979-511-43: 750 mg/3 mL (250 mg/mL) testosterone undecanoate sterile injectable solution is provided in an amber glass vial with silver-colored crimp seal and gray plastic cap.  Each vial is individually packaged in a carton box. Store at controlled room temperature 25ºC (77ºF); excursions permitted to 15ºC - 30ºC (59ºF - 86ºF) [See USP controlled room temperature] in its original carton until the date indicated. Before use, each vial should be visually inspected.  Only vials free from particles should be used.  Single Use Vial.  Discard unused portion.

Endogenous androgens, including testosterone and dihydrotestosterone (DHT) are responsible for the normal growth and development of the male sex organs and for maintenance of secondary sex characteristics.  These effects include the growth and maturation of prostate, seminal vesicles, penis, and scrotum; the development of male hair distribution, such as facial, pubic, chest, and axillary hair; laryngeal enlargement; vocal cord thickening; and alterations in body musculature and fat distribution.  Male hypogonadism, a clinical syndrome resulting from insufficient secretion of testosterone, has 2 main etiologies.  Primary hypogonadism is caused by defects of the gonads, such as Klinefelter’s syndrome or Leydig cell aplasia, whereas secondary hypogonadism is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH). Absorption AVEED 750 mg delivers physiologic amounts of testosterone, producing circulation testosterone concentrations that approximate normal concentrations (300-1000 ng/dL) seen in healthy men. Testosterone esters in oil injected intramuscularly are absorbed from the lipid phase.  Cleavage of the undecanoic acid side chain of AVEED by tissue esterases releases testosterone. Following intramuscular injection of 750 mg of AVEED, serum testosterone concentrations reach a maximum after a median of 7 days (range 4 to 42 days) then slowly decline (Figure 3).  Steady-state serum testosterone concentration was achieved with the third injection of AVEED at 14 weeks.       Figure 3 shows the mean serum total testosterone concentration-time profile during the third injection interval (at steady state, 14 to 24 weeks) for hypogonadal men (less than 300 ng/dL) given 750 mg AVEED at initiation, at 4 weeks, and every 10 weeks thereafter.  Intramuscular injection of 750 mg of AVEED generates mean steady-state serum total testosterone concentrations in the normal range for 10 weeks.                                                         Figure 3:   Mean (SD) Serum Total Testosterone                                                                  Concentrations (ng/dL) at 14 to 24 Weeks                                                      Distribution Circulating testosterone is chiefly bound in the serum to sex hormone-binding globulin (SHBG) and albumin. Approximately 40% of testosterone in plasma is bound to SHBG, 2% remains unbound (free), and the rest is loosely bound to albumin and other proteins.  Metabolism Testosterone undecanoate is metabolized to testosterone via ester cleavage of the undecanoate group. The mean (SD) maximum concentration of testosterone undecanoate was 90.9 (68.8) ng/dL on Day 4 following injection of AVEED. Testosterone undecanoate was nearly undetectable 42 days following injection of AVEED. Testosterone is metabolized to various 17-keto steroids through 2 different pathways.  The major active metabolites of testosterone are estradiol and DHT.  DHT concentrations increased in parallel with testosterone concentrations during AVEED treatment.  Average DHT concentrations during a dosing interval ranged from 244 to 451 ng/dL. The mean DHT to testosterone ratios ranged from 0.05 to 0.07. Excretion There is considerable variation in the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes. About 90% of a testosterone dose given intramuscularly is excreted in the urine as glucuronic and sulfuric acid-conjugates of testosterone or as metabolites.  About 6% of a dose is excreted in the feces, mostly in the unconjugated form. Inactivation of testosterone occurs primarily in the liver.  Effect of Body Weight and Body Mass Index (BMI) Analysis of serum testosterone concentrations from 117 hypogonadal men in the 84-week clinical study of AVEED indicated that serum testosterone concentrations achieved were inversely correlated with the patient’s body weight.  In 60 patients with pretreatment body weight of ≥100 kg, the mean (±SD) serum testosterone average concentration was 426 ± 104 ng/dL.  A higher serum testosterone average concentration (568 ± 139 ng/dL) was observed in 57 patients weighing 65 to 100 kg.  A similar trend was also observed for maximum serum testosterone concentrations. In 70 patients with pretreatment BMIs of >30 kg/m 2 , the mean (±SD) serum testosterone average concentration was 445 ± 116 ng/dL.  Higher serum testosterone average concentrations (579 ± 101 ng/dL and 567± 155ng/dL) were observed in patients with BMIs <26 kg/m 2 and 26 to 30 kg/m 2 , respectively.  A similar trend was also observed for maximum serum testosterone concentrations. Figure3

Carcinogenesis Testosterone has been tested by subcutaneous injection and implantation in mice and rats. In mice, the implant induced cervical-uterine tumors, which metastasized in some cases. There is suggestive evidence that injection of testosterone into some strains of female mice increases their susceptibility to hepatoma. Testosterone is also known to increase the number of tumors and decrease the degree of differentiation of chemically induced carcinomas of the liver in rats. Mutagenesis AVEED was negative in the in vitro Ames assays, the chromosomal aberration assay in human lymphocytes, and in the in vivo mouse micronucleus assay. Impairment of Fertility The administration of exogenous testosterone has been reported to suppress spermatogenesis in the rat, dog, and non-human primates, which was reversible on cessation of the treatment.

AVEED was evaluated for efficacy in an 84-week, single-arm, open-label, multicenter study of 130 hypogonadal men.  Eligible patients weighed at least 65 kg, were 18 years of age and older (mean age 54.2 years), and had a morning serum total testosterone concentration <300 ng/dL (mean screening testosterone concentration 215 ng/dL).  Patients were caucasian (74.6%), black (12.3%), Hispanic (10.8%), and of other ethnicities (2.3%).  The mean BMI was 32 kg/m 2 .  All patients received injections of AVEED 750 mg at baseline, at 4 weeks, and then every 10 weeks thereafter. The primary endpoint was the percentage of patients with average serum total testosterone concentration (C avg ) within the normal range (300-1000 ng/dL) after the third injection, at steady state.  The secondary endpoint was the percentage of patients with maximum total testosterone concentration (C max ) above 3 pre-determined limits: greater than 1500 ng/dL, between 1800 and 2499 ng/dL, and greater than 2500 ng/dL. A total of 117 out of 130 hypogonadal men completed study procedures through Week 24 and were included in the evaluation of testosterone pharmacokinetics after the third AVEED injection. Ninety-four percent (94%) of patients maintained a C avg within the normal range (300 to 1000 ng/dL).  The percentages of patients with C avg below the normal range (less than 300 ng/dL) and above the normal range (greater than 1000 ng/dL) were 5.1% and 0.9%, respectively. Table 2 summarizes the mean (SD) serum total testosterone pharmacokinetic parameters at steady state for these 117 patients. Table 2: Mean (SD) Serum Total Testosterone Concentrations at Steady State   AVEED 750 mg (N=117) C avg (0 to 10 weeks) (ng/dL) 495 (142) C max (ng/dL) 891 (345) C min (ng/dL) 324 (99) C avg = average concentration; C max = maximum concentration; C min = minimum concentration The percentage of patients with C max >1500 ng/dL was 7.7%.  No patient had a C max >1800 ng/dL.

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