turn into [4:4 ng/mL during the 84-week treatment period. A total of 725 hypogonadal men received intramuscular testosterone undecanoate in a total of 7 controlled clinical trials. In these clinical trials, the dose and dose frequency of intramuscular testosterone undecanoate varied from 750 mg to 1000 mg, and from every 9 weeks to every 14 weeks. Several of these clinical trials incorporated additional doses upon initiation of therapy (e.g., loading doses). In addition to those adverse reactions noted in Table 1, the following adverse events were reported by at least 3% of patients in these trials, irrespective of the investigator s assessment of relationship to study medication: sinusitis, prostatitis, arthralgia, nasopharyngitis, upper respiratory tract infection, bronchitis, back pain, hypertension, diarrhea and headache. Pulmonary Oil Microembolism (POME) and Anaphylaxis in Controlled Clinical Studies Adverse events attributable to pulmonary oil microembolism and anaphylaxis were reported in a small number of patients in controlled clinical trials. In the 84-week clinical trial of Aveed, 1 patient experienced a mild coughing fit lasting 10 minutes after his third injection, which was retrospectively attributed to POME. In another clinical trial of intramuscular testosterone undecanoate (1000 mg), a hypogonadal male patient experienced the urge to cough and respiratory distress at 1 minute after his tenth injection, which was also retrospectively attributed to POME. During a review that involved adjudication of all cases meeting specific criteria, 9 POME events in 8 patients and 2 events of anaphylaxis among 3,556 patients treated with intramuscular testosterone undecanoate in 18 clinical trials were judged to have occurred. 6.2 Postmarketing Experience The following adverse reactions 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 establish a causal relationship to drug exposure. Pulmonary Oil Microembolism (POME) and Anaphylaxis 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 post-approval 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 post-approval 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 post-marketing clinical trials and during post-approval use 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, gamma-glutamyltransferase 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: stroke, cerebrovascular insufficiency, reversible ischemic neurological deficiency, transient ischemic attack Psychiatric Disorders: aggression, anxiety, depression, insomnia, irritability, Korsakoff s psychosis non-alcoholic, 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: azoospermia, 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. Drug Interactions 7.1 Insulin 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. 7.2 Oral Anticoagulants 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. 7.3 Corticosteroids 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. USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category X: Aveed is contraindicated in pregnant women or in women who may become pregnant. Testosterone is teratogenic and may cause fetal harm . Exposure of a fetus to androgens, such as testosterone, may result in varying degrees of virilizations. If this drug is used in pregnancy or if the patient becomes pregnant while taking this drug, the patient should be made aware of the potential hazard to the fetus. 8.3 Nursing Mothers Although it is not known how much testosterone transfers into human milk, Aveed is contraindicated in nursing women because of the potential for serious adverse reactions in nursing infants . 8.4 Pediatric Use 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. 8.5 Geriatric Use 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 the153 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 )] . 8.6 Renal Impairment No studies were conducted in patients with renal impairment. 8.7 Hepatic Impairment No studies were conducted in patients with hepatic impairment. Drug Abuse and Dependence 9.1 Controlled Substance Aveed contains testosterone, a Schedule III controlled substance in the Controlled Substances Act. 9.2 Abuse Drug abuse is intentional non-therapeutic use of a drug, even once, for its rewarding psychological and physiological effects. Abuse and misuse of testosterone are seen in male and female adults and adolescents. Testosterone, often in combination with other anabolic androgenic steroids (AAS), and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse of men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice. Abuse-Related Adverse Reactions Serious adverse reactions have been reported in individuals who abuse anabolic androgenic steroids, and include cardiac arrest, myocardial infarction, hypertrophic cardiomyopathy, congestive heart failure, cerebrovascular accident, hepatotoxicity, and serious psychiatric manifestations, including major depression, mania, paranoia, psychosis, delusions, hallucinations, hostility and aggression. The following adverse reactions have also been reported in men: transient ischemic attacks, convulsions, hypomania, irritability, dyslipidemias, testicular atrophy, subfertility, and infertility. The following additional adverse reactions have been reported in women: hirsutism, virilization, deepening of voice, clitoral enlargement, breast atrophy, male-pattern baldness, and menstrual irregularities. The following adverse reactions have been reported in male and female adolescents: premature closure of bony epiphyses with termination of growth, and precocious puberty. Because these reactions are reported voluntarily from a population of uncertain size and may include abuse of other agents, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. 9.3 Dependence Behaviors Associated with Addiction Continued abuse of testosterone and other anabolic steroids, leading to addiction is characterized by the following behaviors: Taking greater dosages than prescribed Continued drug use despite medical and social problems due to drug use Spending significant time to obtain the drug when supplies of the drug are interrupted Giving a higher priority to drug use than other obligations Having difficulty in discontinuing the drug despite desires and attempts to do so Experiencing withdrawal symptoms upon abrupt discontinuation of use Physical dependence is characterized by withdrawal symptoms after abrupt drug discontinuation or a significant dose reduction of a drug. Individuals taking supratherapeutic doses of testosterone may experience withdrawal symptoms lasting for weeks or months which include depressed mood, major depression, fatigue, craving, restlessness, irritability, anorexia, insomnia, decreased libido and hypogonadotropic hypogonadism. Drug dependence in individuals using approved doses of testosterone for approved indications has not been documented. . Overdosage There 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: this subject had serum testosterone levels of up to 11,400 ng/dL with a cerebrovascular accident. Treatment of overdosage would consist of discontinuation of Aveed together with appropriate symptomatic and supportive care. Aveed Description 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. Aveed - Clinical Pharmacology 12.1 Mechanism of Action 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 two 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). 12.3 Pharmacokinetics 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 42 days) then slowly decline (Figure 3). Steady state serum testosterone concentration was achieved with the 3 rd injection of Aveed at 14 weeks. Figure 3 shows the mean serum total testosterone concentration-time profile during the 3 rd injection interval (at steady state, 14-24 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 14-24 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 two 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:T 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 body mass index 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]} FEATURED: CAR-T Cell Therapy Overview Mechanism of Action KTE-C19 Studies KTE-C19 Cancer Targets Adverse Events Manufacturing Drug Status Rx Availability Prescription only X Pregnancy Category Not for use in pregnancy 3 CSA Schedule Moderate abuse potential Approval History Drug history at FDA WADA Class Anti-Doping Classification Manufacturer Endo Pharmaceuticals Inc. Drug Class Androgens and anabolic steroids Related Drugs androgens and anabolic steroids testosterone , AndroGel , Depo-Testosterone , Axiron , Androderm Hypogonadism, Male testosterone , AndroGel , Depo-Testosterone , Axiron , Androderm , Testim , HCG , Fortesta , Testopel , methyltestosterone , Pregnyl , Ovidrel , chorionic gonadotropin (hcg) , Novarel , Gonal-f , Delatestryl , Natesto , Android , Striant , Methitest , Halotestin , Follistim , Chorex , More... Aveed Rating 4 User Reviews 5.2 /10 4 User Reviews 5.2 Rate it!} } traditional
on no account Aveed most suitable
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