Jatenzo

RECENT MAJOR CHANGES Boxed Warning, Increases in Blood Pressure Removed 03/2025 Indications and Usage (1) 03/2025 Contraindications, Men with “age related hypogonadism” (4) Removed 03/2025 Warnings and Precautions , Venous Thromboembolism (5.2) 03/2025 Warnings and Precautions, Blood Pressure Increases (5.4) 03/2025 Warnings and Precautions, Cardiovascular Risk (5.3) Removed 03/2025 Boxed Warning, Increases in Blood Pressure Removed 07/2025 Indications and Usage ( 1 ) 07/2025 Contraindications, Men with “age related hypogonadism” ( 4 ) Removed 07/2025 Warnings and Precautions, Venous Thromboembolism ( 5.2 ) 07/2025 Warnings and Precautions, Blood Pressure Increases ( 5.4 ) 07/2025 Warnings and Precautions, Cardiovascular Risk ( 5.3 ) Removed 07/2025

1 INDICATIONS AND USAGE JATENZO (testosterone undecanoate) 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): testicular failure due to conditions such as cryptorchidism, bilateral torsion, orchitis, vanishing testis syndrome, orchiectomy, Klinefelter 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. Limitations of use: Safety and efficacy of JATENZO in men with “age-related hypogonadism” have not been established. Safety and efficacy of JATENZO in males less than 18 years old have not been established [ see Use in Specific Populations ( 8.4 ) ]. JATENZO (testosterone undecanoate) 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 JATENZO in men with “age-related hypogonadism” have not been established ( 1 ) Safety and efficacy of JATENZO in males less than 18 years old have not been established ( 1 , 8.4 ).

2 DOSAGE AND ADMINISTRATION Prior to initiating JATENZO, 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 concentrations are below the normal range ( 2.1 ). Take JATENZO with food ( 2.2 ). Starting dose: 237 mg orally once in the morning and once in the evening. Adjust the dose to a minimum of 158 mg twice daily and a maximum of 396 mg twice daily based on serum testosterone drawn 6 hours after the morning dose at least 7 days after starting treatment or following dose adjustment and periodically thereafter ( 2.2 ). 2.1 Confirmation of Hypogonadism Before Initiation of JATENZO Prior to initiating JATENZO, 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 testosterone concentrations are below the normal range. 2.2 Dosing and Dose Adjustment Information Individualize the dosage of JATENZO based on the patient's serum testosterone concentration response to the drug. The recommended starting dose is 237 mg taken orally twice daily, once in the morning and once in the evening. Take JATENZO with food. Dose Adjustment To ensure proper dose adjustment, measure serum testosterone concentrations 6 hours after the morning dose in plain tubes, clotted at room temperature for 30 minutes prior to centrifugation. Adjust the JATENZO dose based on this serum testosterone measurement as shown in Table 1. Wait seven days after starting treatment or adjusting the dose before checking the serum testosterone concentration. Thereafter, periodically monitor serum testosterone concentrations 6 hours after the morning dose. Administer the same dose in the morning and evening. The minimum recommended dose is 158 mg twice daily. The maximum recommended dose is 396 mg (two 198 mg capsules) twice daily. Table 1: JATENZO Dose Adjustment Scheme Testosterone Concentration in Serum From Plain Tube Drawn 6 hours After Morning Dose Current JATENZO Dose (mg, twice daily) New JATENZO Dose (mg, twice daily) Less than 425 ng/dL 158 198 198 237 237 316 (two 158 mg capsules) 316 (two 158 mg capsules) 396 (two 198 mg capsules) 425 ng/dL – 970 ng/dL No Dose Change More than 970 ng/dL 396 (two 198 mg capsules) 316 (two 158 mg capsules) 316 (two 158 mg capsules) 237 237 198 198 158 158 Discontinue Treatment

3 DOSAGE FORMS AND STRENGTHS JATENZO capsules for oral use are available in three strengths: The 158 mg testosterone undecanoate capsules are opaque red and imprinted with “158” in white ink. The 198 mg testosterone undecanoate capsules are opaque white and imprinted with “198” in red ink. The 237 mg testosterone undecanoate capsules are opaque orange and imprinted with “237” in white ink. JATENZO (testosterone undecanoate) capsules for oral use are available in the following strengths: 158 mg, 198 mg, 237 mg ( 3 ).

4 CONTRAINDICATIONS JATENZO is contraindicated in: 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 ) ]. Men with known hypersensitivity to JATENZO or any of its ingredients [ see Description ( 11 ) ]. Men with breast cancer or known or suspected prostate cancer ( 4 , 5.3 ). Women who are pregnant. Testosterone may cause fetal harm ( 4 , 5.6 , 8.1 , 8.2 ). Known hypersensitivity to JATENZO or any of its ingredients ( 4 ).

6 ADVERSE REACTIONS Most common adverse reactions (incidence > 2%): polycythemia, diarrhea, dyspepsia, eructation, peripheral edema, nausea, increased hematocrit, headache, prostatomegaly, and hypertension ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Tolmar, Inc. at 1-844-4TO-LMAR or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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 JATENZO was evaluated in a randomized, controlled clinical study with 166 patients treated with JATENZO twice daily with morning and evening meals for approximately 4 months. All patients were started on 237 mg twice daily, then the dose was titrated to 158 mg, 198 mg, 316 mg, or 396 mg twice daily to achieve testosterone concentrations in the eugonadal range. Table 2 summarizes adverse reactions (≥2%) reported in this 4-month study. Table 2: Number (%) of Patients with Adverse Reactions ≥ 2% in a 4-Month Study with JATENZO Among the 569 patients who received JATENZO in all Phase 2 and 3 trials combined, the following adverse reactions were reported in >2% of patients: polycythemia, diarrhea, dyspepsia, eructation, peripheral edema, nausea, increased hematocrit, headache, prostatomegaly, and hypertension. Three of the 166 patients (1.8%) in the 4-month study experienced adverse reactions that led to premature discontinuation from the study, including rash (n=1) and headache (n=2). Preferred Term Overall (N = 166) n (%) Headache 8 (4.8) Hematocrit increased 8 (4.8) Hypertension 6 (3.6) High-density lipoprotein decreased 5 (3.0) Nausea 4 (2.4) BP Increases In the 4-month clinical study, 24-hour ABPM was conducted on 166 patients. ABPM was conducted at baseline and at Day 139 of JATENZO therapy. A total of 135 patients had acceptable ABPM recordings at both time periods and were at least 85% compliant with study drug. In that group, the mean change in 24-hour systolic BP and diastolic BP from baseline to final on-treatment visit on Day 139 (n=135) was +4.9 mm Hg (95% CI 3.5, 6.4) and +2.5 mm Hg (95% CI 1.5, 3.6), respectively. In patients with a history of hypertension who were receiving antihypertensive therapy, the mean ABPM systolic and diastolic BP increased by 5.4 mm Hg [95% CI 3.3, 7.6] and 3.2 mm Hg [95% CI 1.7, 4.7], respectively [n=67]. In patients with no history of hypertension, the mean ABPM systolic and diastolic blood pressure increased by 4.4 mm Hg [95% CI 2.3, 6.4] and 1.8 mm Hg [95% CI 0.2, 3.3], respectively [n=63]. Twelve (7.2%) patients on JATENZO either started antihypertensive medications or had their antihypertensive regimen increased during the study. A total of 6 patients were reported to have an adverse reaction of hypertension (2 patients with hypertension and 4 patients with worsening hypertension), and 3 were reported to have an adverse reaction of increased blood pressure. HR Increases JATENZO increased mean heart rate by an average of 2.2 beats per minute (bpm) [95% CI (1.0, 3.3), N=135] during the study. Patients without a history of hypertension had a greater average increase in mean heart rate (2.7 bpm [95% CI (0.8, 4.6), N=63]) compared to patients with treated hypertension (1.9 bpm [95% CI (0.3, 3.5), N=67)]). Increases in Hematocrit Increases in hematocrit were reported in 8 of the 166 (4.8%) patients, which occurred in the second half of the study. None of these increases led to premature discontinuation of JATENZO. Headaches Headaches were reported in 8 of the 166 patients (4.8%) of which three required treatment with analgesics or non-steroidal anti-inflammatory drugs and 2 led to premature discontinuation from the study. Five of these 8 patients had headache events that resolved within 1 to 2 days. Depression and suicidal ideation Two of the 166 pati …

7 DRUG 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 [see Warnings and Precautions ( 5.4 )].

8 USE IN SPECIFIC POPULATIONS Geriatric Patients: There are insufficient long-term safety data to assess the potential risks of cardiovascular disease and prostate cancer ( 8.5 ). 8.1 Pregnancy Risk Summary JATENZO 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 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 female rats and their offspring exposed to doses approximately twice those used for testosterone replacement therapy. 8.2 Lactation Risk Summary JATENZO is not indicated for use in women. 8.3 Females and Males of Reproductive Potential Infertility During treatment with large doses of exogenous androgens, including JATENZO, spermatogenesis may be suppressed through feedback inhibition of the hypothalamic-pituitary-testicular axis [see Warnings and Precautions ( 5.7 )] , 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. 8.4 Pediatric Use The safety and efficacy of JATENZO 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 involved in controlled clinical studies utilizing JATENZO to determine whether efficacy or safety in those over 65 years of age differs from younger subjects. No patients over 65 years of age were enrolled in the 4-month efficacy and safety clinical study utilizing JATENZO. Additionally, there is insufficient long-term safety data in geriatric patients utilizing JATENZO 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 )].

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, 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 syndrome or Leydig cell aplasia, whereas secondary hypogonadism (also known as hypogonadotropic hypogonadism) is the failure of the hypothalamus (or pituitary) to produce sufficient gonadotropins (FSH, LH).

11 DESCRIPTION JATENZO (testosterone undecanoate) for oral use is provided as a gelatin capsule containing testosterone undecanoate, a fatty-acid ester of testosterone. Testosterone undecanoate is a white to off-white yellow crystalline powder. Testosterone, an androgen, is formed by cleavage of the ester side chain of testosterone undecanoate. Testosterone undecanoate is chemically described as 17β-hydroxyandrost-4-en-3-one undecanoate. It has the empirical formula of C 30 H 48 O 3 and the molecular weight of 456.7. The structural formula for testosterone undecanoate is presented in Figure 1. Figure 1: Testosterone Undecanoate JATENZO capsules are available in three strengths of 158 mg, 198 mg, and 237 mg. The 158 mg strength is an opaque red capsule that contains 158 mg of testosterone undecanoate and is imprinted with “158” in white ink. The 198 mg strength is an opaque white capsule that contains 198 mg of testosterone undecanoate and is imprinted with “198” in red ink. The 237 mg strength is an opaque orange capsule that contains 237 mg of testosterone undecanoate and is imprinted with “237” in white ink. All capsule strengths also contain oleic acid, polyoxyl 40 hydrogenated castor oil (Cremophor RH 40), borage seed oil, peppermint oil, and butylated hydroxytoluene as inactive ingredients. Gelatin capsule shells are composed of the following inactive ingredients: Gelatin, sorbitol, glycerin, and purified water in all strengths, iron oxide red in 158 mg, FD&C Yellow #6 in 158 and 237 mg, and titanium dioxide in 198 and 237 mg capsules. Figure 1

10 OVERDOSAGE There is a single report of acute overdosage with use of an approved injectable testosterone product: this subject had serum testosterone concentrations of up to 11,400 ng/dL which were implicated in a cerebrovascular accident. One case of overdose with JATENZO was reported in clinical trials. This patient inadvertently took a higher dose than prescribed (474 mg twice daily, which is 20% higher than the maximum recommended dose). He did not report any adverse reactions associated with the overdose. Treatment of overdosage consists of discontinuation of JATENZO and appropriate symptomatic and supportive care.

16 HOW SUPPLIED/STORAGE AND HANDLING JATENZO (testosterone undecanoate) capsules are available in three strengths of 158 mg, 198 mg, and 237 mg. Capsules are packaged as 120 units in wide-mouth, round, white HDPE bottles with white, polypropylene, child resistant caps and induction-sealed liner. 158 mg capsules are opaque red capsules imprinted with “158” in white ink and are supplied in bottles: NDC 69087-158-12. 198 mg capsules are opaque white capsules imprinted with “198” in red ink and are supplied in bottles: NDC 69087-198-12. 237 mg capsules are opaque orange capsules imprinted with “237” in white ink and are supplied in bottles: NDC 69087-237-12. Keep JATENZO out of reach of children. Store at 20°C to 25oC (68°F to 77oF), excursions permitted to 15oC to 30oC (59oF to 86oF). Avoid exposing the capsules to moisture (store in a dry place).