Testosterone Undecanoate
FDA Drug Information • Also known as: Aveed, Jatenzo, Kyzatrex, Tlando
- Brand Names
- Aveed, Jatenzo, Kyzatrex, Tlando
- Route
- ORAL
- Dosage Form
- CAPSULE, LIQUID FILLED
- Product Type
- HUMAN PRESCRIPTION DRUG
Description
11 DESCRIPTION TLANDO (testosterone undecanoate) capsules contain 112.5 mg testosterone undecanoate, an ester of testosterone, for oral administration. Testosterone, an androgen, is formed by cleavage of the ester side chain of testosterone undecanoate. The chemical name of testosterone undecanoate is 17β-undecanoyloxy-4-androsten-3-one. It has an empirical formula of C 30 H 48 O 3 and a molecular weight of 456.7. The structural formula is: Testosterone undecanoate is a white to off-white crystalline substance. The inactive ingredients in TLANDO capsules are ascorbyl palmitate, glyceryl monolinoleate, polyethylene glycol 8000, and polyoxyl 40 hydrogenated castor oil. The capsule shell contains black iron oxide, gelatin, and titanium dioxide. The capsule is imprinted with black ink that contains ammonium hydroxide, black iron oxide, propylene glycol, and shellac. Structure
What Is Testosterone Undecanoate Used For?
1 INDICATIONS AND USAGE 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 ).
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Prior to initiating TLANDO, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range ( 2.2 ). Recommended dosage is 225 mg orally twice daily with food ( 2.3 ). Monitor serum testosterone after initiating TLANDO to determine if TLANDO should be continued or discontinued ( 2.3 ). 2.1 Important Dosage Information TLANDO is not substitutable with other oral testosterone undecanoate products. 2.2 Confirmation of Hypogonadism Before Initiation of TLANDO Prior to initiating TLANDO, confirm the diagnosis of hypogonadism by ensuring that serum testosterone concentrations have been measured in the morning on at least two separate days and that these serum testosterone concentrations are below the normal range. 2.3 Recommended Dosage The recommended dosage of TLANDO is 225 mg (taken as two 112.5 mg capsules), orally twice daily, once in the morning and once in the evening. Take with food. Monitoring for Continued Use or Discontinuation Monitor serum testosterone (8 to 9 hours after the morning dose) 3 to 4 weeks after initiating TLANDO, and periodically thereafter. Based on serum testosterone measurements, determine if TLANDO should be continued or discontinued: Serum testosterone 300 - 1080 ng/dL: continue TLANDO Serum testosterone < 300 ng/dL: discontinue TLANDO Serum testosterone > 1080 ng/dL: discontinue TLANDO
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS 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 )] Gynecomastia [see Warnings and Precautions ( 5.11 )] Lipid Changes [see Warnings and Precautions ( 5.12 )] Hypercalcemia [see Warnings and Precautions ( 5.13 )] Decreased Thyroxine-binding Globulin [see Warnings and Precautions ( 5.14 )] Increases in Prolactin [see Warnings and Precautions ( 5.15 )] 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of TLANDO 225 mg twice daily, without dose titration, was evaluated in 233 hypogonadal males during two clinical studies: Study LPCN 1021-18-001 (18-001) and Study LPCN 1021-16-002 (16-002) [see Clinical Studies ( 14 )]. In Study 18-001, an uncontrolled ambulatory blood pressure monitoring (ABPM) study, 138 hypogonadal males were treated with TLANDO 225 mg twice daily with morning and evening meals for approximately four months. Patients had a median age of 54 years (range 26-75), 79% were White, 18% were Black, and 2% were Asian. In 138 hypogonadal male patients, 70% (n=96) were obese (BMI≥30 kg/m 2 ), 24% (n=33) reported a history of type 2 diabetes, and 48% (n=66) reported a history of hypertension. Table 1 summarizes adverse reactions ( > 2%) reported in patients receiving TLANDO in Study 18-001. Table 1. Adverse Reactions ≥ 2% in Patients Receiving TLANDO in Study 18-001 Adverse Reaction Overall (N=138) n (%) Hypertension 7 (5.1) Hematocrit increased 6 (4.3) Upper respiratory tract infection 5 (3.6) Four of the 138 patients (2.9%) in Study 18-001 reported adverse reactions that led to premature discontinuation from the study, including dizziness (n=1), weight increased (n=1), insomnia (n=1), and hypertension (n=2). In Study 16-002, 95 hypogonadal males were treated with TLANDO 225 mg twice daily with morning and evening meals for approximately 24 days. The dose of TLANDO was not titrated. Patients had a median age of 56 years (range 29-74), 81% were White, 16% were Black, 2% were mixed race, and 1% were Asian; 26% were Hispanic. In 95 hypogonadal male patients, 70% (n=66) were obese (BMI≥30 kg/m 2 ), 23% (n=22) reported a history of type 2 diabetes, and 50% (n=47) reported a history of hypertension. Table 2 summarized adverse reactions ( > 2%) reported during Study 16-002 in patients receiving TLANDO. Table 2. Adverse Reactions ≥2% in Patients Receiving TLANDO in Study 16-002 Adverse Reaction Overall (N=95) n (%) Blood prolactin increased 6 (6.3) Weight increased 2 (2.1) Headache 2 (2.1) Musculoskeletal pain 2 (2.1) One of the 95 patients (1.1%) in the 24-day study reported an adverse reaction (gastric ulcer hemorrhage) that led to premature discontinuation from the study. Blood Pressure Increases In Study 18-001 24-hour ambulatory blood pressure monitoring (ABPM) was conducted in 138 male patients, 126 of whom completed the study. ABPM was conducted at 2 distinct 24-hour time periods: at baseline and following approximately 16...
Drug Interactions
7 DRUG INTERACTIONS 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. 7.2 Oral Anticoagulants Changes in anticoagulant activity may be seen with androgens. Frequent monitoring of INR and prothrombin time may be necessary in patients taking anticoagulants, 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 should be monitored cautiously, particularly in patients with cardiac, renal or hepatic disease. 7.4 Drugs that May Also Increase Blood Pressure Some prescription drugs and nonprescription analgesic and cold medications can increase blood pressure. Concomitant administration of these medications with TLANDO may lead to additional increases in blood pressure [ see Warnings and Precautions ( 5.4 ) ] .
Contraindications
4 CONTRAINDICATIONS 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 )
Pregnancy and Breastfeeding
8.1 Pregnancy Risk Summary TLANDO is contraindicated in pregnant women and not indicated for use in females [ see Contraindications ( 4 )] . Testosterone is teratogenic and may cause fetal harm when administered to a pregnant woman based on data from animal studies (see Data ) and its mechanism of action [ see Clinical Pharmacology ( 12.1 ) ] . Exposure of a female fetus to androgens may result in varying degrees of virilization. In animal developmental 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 females and offspring in rats exposed to doses approximately twice those used for testosterone replacement therapy.
Overdosage
10 OVERDOSAGE 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 consists of discontinuation of TLANDO and appropriate symptomatic and supportive care.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING 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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.