Testosterone: uses, appearance and warnings

TLANDO 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 conditions such as 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 [see Dosage and Administration ( 2.2 )]. 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 [see Dosage and Administration ( 2.2 )]. Limitations of Use Safety and efficacy of TLANDO in males less than 18 years old have not been established [see Use in Specific Populations ( 8.4 )] . Safety and efficacy of TLANDO in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established [see Use in Specific Populations ( 8.5 )] . TLANDO is an androgen indicated for testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone ( 1 ). Limitations of Use Safety and efficacy of TLANDO in males less than 18 years old have not been established ( 1 ). Safety and efficacy of TLANDO in men with “age-related hypogonadism” have not been established ( 1 ).

Capsules: 112.5 mg, white opaque body imprinted with “112” in black ink and grey opaque cap, banded with a colorless gelatin band. Capsules: 112.5 mg ( 3 )

TLANDO capsules for oral administration are available containing 112.5 mg of testosterone undecanoate. The capsules have a white opaque body imprinted with “112” in black ink and a grey opaque cap, banded with a colorless band. TLANDO capsules are supplied in HDPE bottles with a foil liner and a child resistant cap. Bottles of 120 capsules: NDC 74676-0112-2. Store at 20ºC to 25°C (68ºF to 77°F); excursions permitted to 15ºC to 30°C (59ºF to 86°F). [See USP Controlled Room Temperature]. Dispose of unused TLANDO via a take-back option. If a take-back option is unavailable, follow FDA instructions at www.fda.gov/drugdisposal.

TLANDO is contraindicated in: Patients 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 )] . Known hypersensitivity to testosterone undecanoate or any of TLANDO’s ingredients [see Description ( 11 )]. Carcinoma of the breast or known or suspected carcinoma of the prostate ( 4 ) Women who are pregnant. Testosterone may cause fetal harm ( 4 , 5.6 , 8.1 ) Hypersensitivity to TLANDO or any of its ingredients ( 4 )

Polycythemia : Monitor hematocrit approximately every 3 months during the first year after beginning TLANDO and then every 6 months thereafter during treatment. Discontinue TLANDO if necessary ( 5.1 ). Venous thromboembolism (VTE) : VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients using testosterone products. Discontinue TLANDO if VTE is suspected and initiate appropriate workup and management ( 5.2 ). Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer : Monitor patients with benign prostatic hyperplasia (BPH) for worsening of signs and symptoms of BPH. Evaluate patients for prostate cancer, including monitoring prostate specific antigen (PSA) prior to initiating and during treatment with androgens ( 5.3 ) Blood Pressure Increases: TLANDO can increase blood pressure, which can increase cardiovascular risk over time. Measure blood pressure periodically. Not recommended for use in men with uncontrolled hypertension ( 5.4 ) Abuse of Testosterone and Monitoring of Serum Testosterone : If testosterone use at doses higher than recommended for the approved indication and in combination with other anabolic androgenic steroids is suspected, check serum testosterone concentration ( 5.5 ). Potential for Adverse Effects on Spermatogenesis : TLANDO may cause azoospermia ( 5.7 , 8.3 ). Edema : Edema, with or without congestive heart failure (CHF) may occur in patients with preexisting cardiac, renal, or hepatic disease. Discontinue TLANDO and initiate appropriate workup ( 5.9 ). Sleep Apnea: TLANDO may potentiate sleep apnea in those with risk factors ( 5.10 ). Lipid Changes : Testosterone may affect serum lipid profile. Monitor patient lipid concentrations; if necessary, adjust dosage of lipid lowering drug(s) or discontinue TLANDO ( 5.12 ). Increases in Prolactin : Monitor serum prolactin levels prior to initiation of TLANDO and 3 to 4 months after starting TLANDO. Discontinue TLANDO if serum prolactin levels remain elevated ( 5.15 ). 5.1 Polycythemia Increases in hematocrit levels, reflective of increases in red blood cell mass, may require discontinuation of TLANDO. Check hematocrit prior to initiating TLANDO. Evaluate hematocrit approximately every 3 months during the first year of treatment, and then every 6 months thereafter while the patient is taking TLANDO. If hematocrit becomes elevated, stop TLANDO until hematocrit decreases to an acceptable concentration. If TLANDO is restarted and again causes hematocrit to become elevated, stop TLANDO permanently. An increase in red blood cell mass may increase the risk of thromboembolic events [ see Warnings and Precautions ( 5.2 ) ] . 5.2 Venous Thromboembolism There have been post marketing reports of venous thromboembolic events, including deep vein thrombosis (DVT) and pulmonary embolism (PE), in patients using testosterone replacement products such as TLANDO. 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%) [see Adverse Reactions ( 6.1 )]. 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 TLANDO and initiate appropriate workup and management [see Adverse Reactions ( 6.2 )] . 5.3 Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer Patients with BPH treated with androgens are at an increased risk for worsening of signs and symptoms of BPH. Monitor patients with BPH for worsening signs and symptoms. Patients treated with androgens may be at increased risk for prostate cancer. Evaluate patients for prostate cancer, including measurement of prostate specific antigen (PSA), prior to initiating and during treatment with androgens [see Contraindications ( 4 )] . 5.4 Blood Pressure Increases TLANDO can increase blood pressure. Based on ambulatory blood pressure monitoring in Study 18-001, TLANDO increased mean systolic/diastolic BP by 4.3/1.4 mmHg from baseline after 4 months of treatment. In patients with hypertension on antihypertensive therapy, TLANDO increased the mean systolic/diastolic BP by 4.8/1.6 mm Hg from baseline. [see Adverse Reactions ( 6.1 )] . 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 mmHg from baseline to 36 months, whereas a mean decrease from baseline of 0.5 mmHg was observed in the placebo group at this timepoint, for a mean between group difference of 1.5 mmHg. 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 BP periodically in men using TLANDO, especially men with hypertension. TLANDO is not recommended for use in patients with uncontrolled hypertension. 5.5 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. …

Most common adverse reactions (incidence ≥ 2%): increased blood prolactin, hypertension, increased hematocrit, upper respiratory tract infection, weight increased, headache, and musculoskeletal pain ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Verity Pharma at 1-844-837-4891 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . The following clinically significant adverse reactions are discussed elsewhere in the labeling: Polycythemia [see Warnings and Precautions ( 5.1 )] Venous Thromboembolism [see Warnings and Precautions ( 5.2 )] Worsening of Benign Prostatic Hyperplasia (BPH) and Potential Risk of Prostate Cancer [see Warnings and Precautions ( 5.3 )] Blood Pressure Increases [see Warnings and Precautions ( 5.4 )] Hepatic Adverse Effects [see Warnings and Precautions ( 5.8 )] Edema [see Warnings and Precautions ( 5.9 )] Sleep Apnea [see Warnings and Precautions ( 5.10 )] Gyn …

Insulin: In patients with diabetes, concomitant use with TLANDO may decrease blood glucose and insulin requirements ( 7.1) . Oral Anticoagulants: Concomitant use with TLANDO may cause changes in anticoagulant activity. Monitor International Normalized Ratio and prothrombin time frequently ( 7.2 ). Corticosteroids: Concomitant use with TLANDO may result in increased fluid retention. Use with caution, particularly in patients with cardiac, renal, or hepatic disease ( 7.3 ). Drugs that May Also Increase Blood Pressure: Concomitant use with TLANDO may lead to additional increases in blood pressure ( 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, insulin requirements. …