INTERACTIONS 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 ). Concomitant administration of medications that are known to increase blood pressure may lead to additional increases in blood pressure when used with JATENZO ( 7.4 ).
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 Vitamin K Antagonist 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.
7.4 Medications that May Also Increase Blood Pressure Some prescription medications and nonprescription analgesic and cold medications contain drugs known to increase blood pressure. Concomitant administration of these medications with JATENZO may lead to additional increases in blood pressure <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.4 )]</span>.
TLANDO is contraindicated in: Patients with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions ( 5.4 )] . 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 )] . Known hypersensitivity to testosterone undecanoate or any of TLANDO’s ingredients [see Description ( 11 )]. Men with hypogonadal conditions, such as “age-related hypogonadism”, that are not associated with structural or genetic etiologies. The efficacy of TLANDO has not been established for these conditions, and TLANDO can increase BP that can increase the risk of MACE [see Boxed Warning and Warning and Precautions ( 5.1 )] . Carcinoma of the breast or known or suspected carcinoma of the prostate ( 4 ) Women who are pregnant. Testosterone may cause fetal harm ( 4 , 5.7 , 8.1 ) Hypersensitivity to TLANDO or any of its ingredients ( 4 ) Hypogonadal conditions not associated with structural or genetic etiologies ( 4 )
AND PRECAUTIONS Venous thromboembolism (VTE): 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 ( 5.4 ). Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer: Monitor patients with BPH for worsening of signs and symptoms of BPH ( 5.5 ).
Blood Pressure
Increases: Testosterone can increase blood pressure, which can increase cardiovascular risk over time. Measure blood pressure periodically. Not recommended for use in men with uncontrolled hypertension ( 5.6 ) Abuse of Testosterone: Testosterone has been subject to abuse, typically at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids ( 5.7 ). Potential for Adverse Effects on Spermatogenesis: Exogenous administration of androgens may lead to azoospermia ( 5.9 ). Edema: Edema with or without congestive heart failure may be a complication in patients with preexisting cardiac, renal, or hepatic disease ( 5.11 ). Sleep apnea: Sleep apnea may occur in those with risk factors ( 5.13 ). Monitor prostatic specific antigen (PSA), hemoglobin, hematocrit, and lipid concentrations periodically ( 5.3 , 5.5 , 5.14 ).
5.1 Serious Pulmonary Oil Microembolism (POME) Reactions and Anaphylaxis 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 <span class="opacity-50 text-xs">[see Dosage and Administration ( 2.2 , 2.3 ) and Adverse Reactions ( 6.2 )]</span> . 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.
5.2 AVEED Risk Evaluation and Mitigation Strategy (REMS) Program 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.
5.3 Polycythemia 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.
5.4 Venous Thromboembolism (VTE) 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. In the Testosterone Replacement therapy for Assessment of long-term Vascular Events and efficacy ResponSE in hypogonadal men (TRAVERSE) Study, a randomized, double-blind, placebo-controlled, cardiovascular (CV) outcomes study, compared to placebo, topical testosterone gel was associated with a numerically higher incidence of VTE (1.7% vs 1.2%) which included DVT (0.6% vs 0.5%) and PE events (0.9% vs 0.5%) <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span>. 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.
5.5 Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer 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 <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> .
5.6 Blood Pressure Increases AVEED can increase blood pressure. In an ambulatory blood pressure monitoring (ABPM) study, AVEED increased the mean systolic/diastolic blood pressure by 3.1/2.0 mm Hg from baseline after 16 weeks of treatment. In patients with hypertension on antihypertensive therapy, AVEED increased the mean systolic/diastolic BP by 2.1/1.5 mm Hg from baseline. Blood pressure increases can increase cardiovascular (CV) risk over time. The CV risk associated with topical testosterone gel was evaluated in TRAVERSE, a randomized, double-blind, placebo-controlled, CV outcomes study in men with a history of CV disease or multiple CV risk factors. In TRAVERSE, topical testosterone gel increased mean systolic blood pressure by 1.0 mm Hg from baseline to 36 months, whereas a mean decrease from baseline of 0.5 mm Hg was observed in the placebo group at this timepoint, for a mean between-group difference of 1.5 mm Hg. However, the incidences of major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction [MI] and non-fatal stroke, were similar between treatment groups (7% for topical testosterone gel vs 7.3% for placebo) [See Adverse Reactions ( 6.1 )]. Monitor blood pressure periodically in men using AVEED, especially men with hypertension. AVEED is not recommended for use in patients with uncontrolled hypertension.
5.7 Abuse of Testosterone and Monitoring of Serum Testosterone Concentrations 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 <span class="opacity-50 text-xs">[see Drug Abuse and Dependence ( 9 )]</span>. 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.
5.8 Not for Use in Women Due to lack of controlled evaluations in women and potential virilizing effects, AVEED is not indicated for use in women <span class="opacity-50 text-xs">[see Contraindications ( 4 ) and Use in Specific Populations ( 8.1 , 8.2 )]</span> .
5.9 Potential for Adverse Effects on Spermatogenesis 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.
5.10 Hepatic Adverse Effects 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.
5.11 Edema 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.
5.12 Gynecomastia Gynecomastia occasionally develops and occasionally persists in patients being treated for hypogonadism <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.1 )]</span> .
5.13 Sleep Apnea 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.
5.14 Lipid Changes Changes in serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy, such as AVEED. Monitor the lipid profile periodically, particularly after starting testosterone therapy.
5.15 Hypercalcemia 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.
5.16 Decreased Thyroxine-binding Globulin 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.