These Highlights Do Not Include All The Information Needed To Use Kyzatrex® Safely And Effectively. See Full Prescribing Information For Kyzatrex®.

Boxed Warnings, Blood Pressure Increases Removed 07/2025

Contraindications, Hypogonadal conditions not

associated with structural or genetic etiologies (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 (5.4) Removed 07/2025

Limitations of Use

Safety and efficacy of KYZATREX® in males less than 18 years old have not been established [see Use in Specific Populations (8.4)] .

Safety and efficacy of KYZATREX® in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.

Store at 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store the capsules in a dry place avoiding exposure to excessive moisture and humid conditions.

Dispose of unused KYZATREX® via a take-back option. If a take-back option is unavailable, follow FDA instructions at www.fda.gov/drugdisposal.

Androgens, including KYZATREX®, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease [see Adverse Reactions (6.1)]. In addition to discontinuation of the drug, diuretic therapy may be required.

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, and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice.

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 necessitate a decrease in the dose of anti-diabetic medication.

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 KYZATREX® and appropriate symptomatic and supportive care.

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KYZATREX® 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 ₃₀H ₄₈O ₃ and a molecular weight of 456.7 g/mol. The structural formula for testosterone undecanoate is presented in Figure 1.

Figure 1: Testosterone Undecanoate

KYZATREX® (testosterone undecanoate) capsules for oral use are available in three dosage strengths- 100 mg, 150 mg, and 200 mg. The 100 mg strength is an opaque, white capsule imprinted with "MP100" in red ink. The 150 mg strength is an opaque white capsule imprinted with "MP150" in red ink. The 200 mg strength is an opaque white capsule imprinted with "MP200" in red ink. All capsule strengths also contain DL-alpha-tocopheryl acetate (Vitamin E), phytosterol esters, polyoxyl 40 hydrogenated castor oil, and propylene glycol monolaurate as inactive ingredients.

Gelatin capsule shells are composed of the following inactive ingredients: gelatin, glycerin, purified water, sorbitol, and titanium dioxide.

Androgens, including KYZATREX®, can cause increase in hemoglobin or hematocrit, reflective of increase in red blood cell mass. Check hematocrit prior to initiating KYZATREX®. An increase in red blood cell mass may increase the risk of thromboembolic events [see Warnings and Precautions ( 5.2)]. Evaluate hematocrit approximately every 3 months while the patient is on KYZATREX®. If hematocrit becomes elevated, stop KYZATREX® until the hematocrit decreases to an acceptable concentration. If KYZATREX® is restarted and again causes hematocrit to become elevated, permanently discontinue KYZATREX®.

The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung disease.

Gynecomastia may develop and persist in patients being treated for hypogonadism.

The safety and efficacy of KYZATREX® in pediatric patients less than 18 years old have not been established. KYZATREX® is not recommended for use in patients less than 18 years of age because of the potential for acceleration of bone age and premature closure of epiphyses.

Clinical studies of KYZATREX® did not include any patients 65 years of age and older. Therefore, it cannot be determined whether these patients respond differently from younger adult patients. 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 including KYZATREX® may be at risk for worsening of signs and symptoms of BPH [see (see Warnings and Precautions (5.3)] .

In clinical trials, patients receiving KYZATREX® experienced reductions in lipid parameters, including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides [see Adverse Reactions (6.1)]. Changes in the serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy. Monitor the lipid profile periodically, particularly after starting testosterone therapy.

Androgens, including KYZATREX®, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Monitor serum calcium concentrations periodically during treatment with KYZATREX® in these patients.

The efficacy and safety of KYZATREX® were evaluated in Study MRS-TU-2019EXT (NCT04467697) a multi-center, open-label study of approximately 6 months of duration in 155 hypogonadal males.

Patients received KYZATREX® at a starting dose of 200 mg twice daily with meals. The dosage was adjusted on Days 28 and 56 between a minimum dose of 100 mg (single morning dose) and a maximum dose of 800 mg (400 mg twice daily) based on plasma testosterone concentration from a single blood draw between 3 to 5 hours after the morning dose.

The primary efficacy endpoint was the percentage of KYZATREX®-treated patients with mean plasma total testosterone concentration (C _avg) over 24-hours within the normal range of 222-800 ng/dL on the final PK visit of the study at Day 90.

The efficacy population consisted of 139 hypogonadal, males with a median age of 50 years (range 22 to 66 years), 79% were White, 16% were Black, 3% were Asian, and 2% were American Indian, Alaskan Native or Other.

Primary efficacy results are summarized in Table 6.

Secondary endpoints were the percentage of patients with a maximum total testosterone concentration (C _max) meeting three predetermined limits: less than or equal to 1.5 times the upper limit of normal range (ULN) (1200 ng/dL), between 1.8 and 2.5 times ULN (1440-2000 ng/dL), and greater than 2.5 times ULN (2000 ng/dL).

The percentage of patients who received KYZATREX® and had testosterone Cmax threshold less than or equal to 1200 ng/dL, between 1440 and 2000 ng/dL, and greater than 2000 ng/dL at the final PK visit were 88%, 4%, and 0%, respectively.

KYZATREX® is contraindicated in:

• Patients with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (5.34)] .
• 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) ].
• Patients with known hypersensitivity to KYZATREX® or any of its ingredients [see Description (11)] .

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)]

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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.

There is insufficient data to characterize an exposure-response relationship or time course of pharmacodynamics.

-

KYZATREX® 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 syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (folliclestimulating hormone (FSH), luteinizing hormone (LH)) above the normal range.
• Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low serum testosterone concentrations but have gonadotropins in the normal or low range.

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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 gland) to produce sufficient gonadotropins (FSH, LH).

Due to lack of controlled studies in women and potential virilizing effects, KYZATREX® is not indicated for use in women [see Contraindications (4) and Use in Specific Populations ( 8.1 , 8.2 )].

KYZATREX® contains testosterone undecanoate, a Schedule III controlled substance

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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 KYZATREX®.

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 KYZATREX® and initiate appropriate workup and management [see Adverse Reactions ( 6.2)].

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KYZATREX® is not a 17-alpha-alkyl androgen and is not known to cause hepatic adverse effects. However, prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., 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 has produced multiple hepatic adenomas. Patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue KYZATREX® while the cause is evaluated.

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Capsules:

• 100 mg, oval, opaque, white, imprinted with "MP100" in red ink
• 150 mg, oblong, opaque, white, imprinted with "MP150" in red ink
• 200 mg, oblong, opaque, white, imprinted with "MP200" in red ink

KYZATREX® can increase blood pressure. Based on ambulatory blood monitoring in Study MRS-TU-2019EXT, KYZATREX® increased mean systolic/diastolic blood pressure by 1.7/0.6 mm Hg from baseline after 4 months of treatment and 1.8/0.6 mm Hg from baseline after 6 months of treatment [see Adverse Reactions (6.1) ]. In patients with hypertension on antihypertensive therapy, KYZATREX® increased the mean systolic/diastolic BP by 3.4/0.7 mm Hg from baseline after 4 months of treatment and 3.1/1.0 mm Hg from baseline after 6 months of treatment. [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 mm Hg from baseline to 36 months, whereas a mean decrease from baseline of 0.5 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 BP periodically in men using KYZATREX®, especially men with hypertension. KYZATREX® is not recommended for use in patients with uncontrolled hypertension.

The following adverse reactions have been identified during post-approval use of testosterone. Because these 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.

Cardiovascular Disorders: myocardial infarction, stroke

Vascular Disorders: Venous thromboembolism

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 KYZATREX® was evaluated in Study MRS-TU-2019EXT in 155 hypogonadal males [see Clinical Studies (14)]. All patients initially received KYZATREX® 200 mg orally twice daily. If needed, the dosage was titrated to 100 mg once daily in the morning or 100 mg, 300 mg, or 400 mg twice daily to achieve testosterone concentrations in the normal range . After the dosage titration period, patients continued their optimized dose for the remainder of the duration of the 6-month study. The mean duration of exposure was 168 days (range: 1 to 180 days). The median age was 52 years (range: 22 to 66 years); 77% were White, 19% were Black, 3% were Asian, and 2% were American Indian, Alaskan Native or Other.

Table 2 summarizes adverse reactions reported in ≥2% of patients in this 6-month study.

One (0.8%) patient who received KYZATREX® experienced an adverse reaction (acne) that lead to premature discontinuation from the study.

In a 12-month, open-label study in hypogonadal adult males (N=212) who received KYZATREX® 200 mg once daily to 400 mg twice daily (n=202) the following additional adverse reactions were reported: headache, arthralgia, diarrhea, hemoglobin increased, anxiety, constipation, peripheral edema, and PSA increased.

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KYZATREX® is not substitutable with other oral testosterone undecanoate products.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

KYZATREX® capsules are available in three strengths of 100 mg, 150 mg, and 200 mg packaged as 60, 90 and 120 units in wide-mouth, round, white HDPE bottles with white, polypropylene, child resistant caps and induction-sealed liner

100 mg: Oval, opaque, white capsules imprinted with "MP100" in red ink supplied in bottles; NDC 80603-101-11 for 90 capsules and NDC 80603-101-22 for 120 capsules.

150 mg: Oblong, opaque, white capsules imprinted with "MP150" in red ink supplied in bottles; NDC 80603-103-11 for 90 capsules and NDC 80603-103-22 for 120 capsules.

200 mg: Oblong, opaque, white capsules imprinted with "MP200" in red ink supplied in bottles; NDC 80603-105-33 for 60 capsules , NDC 80603-105-11 for 90 capsules and NDC 80603-105-22 for 120 capsules .

Individualize the dosage of KYZATREX® based on the patient's serum testosterone concentration response to the drug.

The recommended starting dose is 200 mg orally twice daily, once in the morning and once in the evening. Take KYZATREX® with food.

A 3-month repeat-dose oral toxicity study in male eugonadal dogs was conducted to evaluate whether phytosterol esters present in the KYZATREX® formulation influenced target organ toxicity due to their structural similarities to sex steroids like testosterone. KYZATREX® doses 2 times the MRHDD (based on mean AUC exposure to testosterone) produced similar effects on androgen-responsive tissues as testosterone undecanoate without phytosterol esters. These included mild to marked effects on the testes (decreased size, germ cell depletion, Leydig cell atrophy), epididymides (aspermia), adrenal glands (vacuolation in the zona fasciculata) and prostate (increased size and glandular hypertrophy/hyperplasia). Following a 4-week treatment-free period, findings in the testes, epididymides, and adrenal glands were not fully reversible at doses of 2 times the MRHDD of KYZATREX® as compared to treatment with the excipients alone, including phytosterol esters. Reversibility was not assessed in testosterone undecanoate groups without phytosterol esters.

Androgens, including KYZATREX®, may decrease concentrations of thyroxin-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.

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.

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With large doses of exogenous androgens, including KYZATREX®, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH, possibly leading to adverse effects on semen parameters including sperm count [see Use in Specific Populations (8.3) ]. Inform patients of this possible risk when deciding whether to use or to continue to use KYZATREX®.

Some prescription medications and nonprescription analgesic and cold medications contain drugs known to increase blood pressure. Concomitant administration of these medications with KYZATREX® may lead to additional increases in blood pressure [see Warnings and Precautions (5.4)].

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Prior to initiating KYZATRE®, 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.

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 [see Drug Abuse and Dependence (9)].

If testosterone abuse is suspected, check testosterone concentrations to ensure they are within therapeutic range [see Dosage and Administration ( 2.2)]. Testosterone levels may remain 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. Also consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

• Patients with BPH who are 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 prior to initiating and during treatment with androgens [see Contraindications (4)].

Limitations of Use

Safety and efficacy of KYZATREX® in males less than 18 years old have not been established [see Use in Specific Populations (8.4)] .

Safety and efficacy of KYZATREX® in men with “age-related hypogonadism” (also referred to as “late-onset hypogonadism”) have not been established.

Store at 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Store the capsules in a dry place avoiding exposure to excessive moisture and humid conditions.

Dispose of unused KYZATREX® via a take-back option. If a take-back option is unavailable, follow FDA instructions at www.fda.gov/drugdisposal.

Androgens, including KYZATREX®, may promote retention of sodium and water. Edema, with or without congestive heart failure, may be a serious complication in patients with pre-existing cardiac, renal, or hepatic disease [see Adverse Reactions (6.1)]. In addition to discontinuation of the drug, diuretic therapy may be required.

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, and not obtained by prescription through a pharmacy, may be abused by athletes and bodybuilders. There have been reports of misuse by men taking higher doses of legally obtained testosterone than prescribed and continuing testosterone despite adverse events or against medical advice.

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 necessitate a decrease in the dose of anti-diabetic medication.

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 KYZATREX® and appropriate symptomatic and supportive care.

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KYZATREX® 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 ₃₀H ₄₈O ₃ and a molecular weight of 456.7 g/mol. The structural formula for testosterone undecanoate is presented in Figure 1.

Figure 1: Testosterone Undecanoate

KYZATREX® (testosterone undecanoate) capsules for oral use are available in three dosage strengths- 100 mg, 150 mg, and 200 mg. The 100 mg strength is an opaque, white capsule imprinted with "MP100" in red ink. The 150 mg strength is an opaque white capsule imprinted with "MP150" in red ink. The 200 mg strength is an opaque white capsule imprinted with "MP200" in red ink. All capsule strengths also contain DL-alpha-tocopheryl acetate (Vitamin E), phytosterol esters, polyoxyl 40 hydrogenated castor oil, and propylene glycol monolaurate as inactive ingredients.

Gelatin capsule shells are composed of the following inactive ingredients: gelatin, glycerin, purified water, sorbitol, and titanium dioxide.

Androgens, including KYZATREX®, can cause increase in hemoglobin or hematocrit, reflective of increase in red blood cell mass. Check hematocrit prior to initiating KYZATREX®. An increase in red blood cell mass may increase the risk of thromboembolic events [see Warnings and Precautions ( 5.2)]. Evaluate hematocrit approximately every 3 months while the patient is on KYZATREX®. If hematocrit becomes elevated, stop KYZATREX® until the hematocrit decreases to an acceptable concentration. If KYZATREX® is restarted and again causes hematocrit to become elevated, permanently discontinue KYZATREX®.

The treatment of hypogonadal men with testosterone may potentiate sleep apnea in some patients, especially those with risk factors such as obesity or chronic lung disease.

Gynecomastia may develop and persist in patients being treated for hypogonadism.

The safety and efficacy of KYZATREX® in pediatric patients less than 18 years old have not been established. KYZATREX® is not recommended for use in patients less than 18 years of age because of the potential for acceleration of bone age and premature closure of epiphyses.

Clinical studies of KYZATREX® did not include any patients 65 years of age and older. Therefore, it cannot be determined whether these patients respond differently from younger adult patients. 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 including KYZATREX® may be at risk for worsening of signs and symptoms of BPH [see (see Warnings and Precautions (5.3)] .

In clinical trials, patients receiving KYZATREX® experienced reductions in lipid parameters, including total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides [see Adverse Reactions (6.1)]. Changes in the serum lipid profile may require dose adjustment of lipid lowering drugs or discontinuation of testosterone therapy. Monitor the lipid profile periodically, particularly after starting testosterone therapy.

Androgens, including KYZATREX®, should be used with caution in cancer patients at risk of hypercalcemia (and associated hypercalciuria). Monitor serum calcium concentrations periodically during treatment with KYZATREX® in these patients.

The efficacy and safety of KYZATREX® were evaluated in Study MRS-TU-2019EXT (NCT04467697) a multi-center, open-label study of approximately 6 months of duration in 155 hypogonadal males.

Patients received KYZATREX® at a starting dose of 200 mg twice daily with meals. The dosage was adjusted on Days 28 and 56 between a minimum dose of 100 mg (single morning dose) and a maximum dose of 800 mg (400 mg twice daily) based on plasma testosterone concentration from a single blood draw between 3 to 5 hours after the morning dose.

The primary efficacy endpoint was the percentage of KYZATREX®-treated patients with mean plasma total testosterone concentration (C _avg) over 24-hours within the normal range of 222-800 ng/dL on the final PK visit of the study at Day 90.

The efficacy population consisted of 139 hypogonadal, males with a median age of 50 years (range 22 to 66 years), 79% were White, 16% were Black, 3% were Asian, and 2% were American Indian, Alaskan Native or Other.

Primary efficacy results are summarized in Table 6.

Secondary endpoints were the percentage of patients with a maximum total testosterone concentration (C _max) meeting three predetermined limits: less than or equal to 1.5 times the upper limit of normal range (ULN) (1200 ng/dL), between 1.8 and 2.5 times ULN (1440-2000 ng/dL), and greater than 2.5 times ULN (2000 ng/dL).

The percentage of patients who received KYZATREX® and had testosterone Cmax threshold less than or equal to 1200 ng/dL, between 1440 and 2000 ng/dL, and greater than 2000 ng/dL at the final PK visit were 88%, 4%, and 0%, respectively.

KYZATREX® is contraindicated in:

• Patients with carcinoma of the breast or known or suspected carcinoma of the prostate [see Warnings and Precautions (5.34)] .
• 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) ].
• Patients with known hypersensitivity to KYZATREX® or any of its ingredients [see Description (11)] .

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)]

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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.

Boxed Warnings, Blood Pressure Increases Removed 07/2025

Contraindications, Hypogonadal conditions not

associated with structural or genetic etiologies (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 (5.4) Removed 07/2025

There is insufficient data to characterize an exposure-response relationship or time course of pharmacodynamics.

-

KYZATREX® 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 syndrome, chemotherapy, or toxic damage from alcohol or heavy metals. These men usually have low serum testosterone concentrations and gonadotropins (folliclestimulating hormone (FSH), luteinizing hormone (LH)) above the normal range.
• Hypogonadotropic hypogonadism (congenital or acquired): gonadotropin or luteinizing hormone-releasing hormone (LHRH) deficiency, pituitary-hypothalamic injury from tumors, trauma, or radiation. These men have low serum testosterone concentrations but have gonadotropins in the normal or low range.

-

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 gland) to produce sufficient gonadotropins (FSH, LH).

Due to lack of controlled studies in women and potential virilizing effects, KYZATREX® is not indicated for use in women [see Contraindications (4) and Use in Specific Populations ( 8.1 , 8.2 )].

KYZATREX® contains testosterone undecanoate, a Schedule III controlled substance

-

-

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 KYZATREX®.

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 KYZATREX® and initiate appropriate workup and management [see Adverse Reactions ( 6.2)].

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KYZATREX® is not a 17-alpha-alkyl androgen and is not known to cause hepatic adverse effects. However, prolonged use of high doses of orally active 17-alpha-alkyl androgens (e.g., 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 has produced multiple hepatic adenomas. Patients should be instructed to report any signs or symptoms of hepatic dysfunction (e.g., jaundice). If these occur, promptly discontinue KYZATREX® while the cause is evaluated.

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Capsules:

• 100 mg, oval, opaque, white, imprinted with "MP100" in red ink
• 150 mg, oblong, opaque, white, imprinted with "MP150" in red ink
• 200 mg, oblong, opaque, white, imprinted with "MP200" in red ink

KYZATREX® can increase blood pressure. Based on ambulatory blood monitoring in Study MRS-TU-2019EXT, KYZATREX® increased mean systolic/diastolic blood pressure by 1.7/0.6 mm Hg from baseline after 4 months of treatment and 1.8/0.6 mm Hg from baseline after 6 months of treatment [see Adverse Reactions (6.1) ]. In patients with hypertension on antihypertensive therapy, KYZATREX® increased the mean systolic/diastolic BP by 3.4/0.7 mm Hg from baseline after 4 months of treatment and 3.1/1.0 mm Hg from baseline after 6 months of treatment. [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 mm Hg from baseline to 36 months, whereas a mean decrease from baseline of 0.5 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 BP periodically in men using KYZATREX®, especially men with hypertension. KYZATREX® is not recommended for use in patients with uncontrolled hypertension.

The following adverse reactions have been identified during post-approval use of testosterone. Because these 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.

Cardiovascular Disorders: myocardial infarction, stroke

Vascular Disorders: Venous thromboembolism

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 KYZATREX® was evaluated in Study MRS-TU-2019EXT in 155 hypogonadal males [see Clinical Studies (14)]. All patients initially received KYZATREX® 200 mg orally twice daily. If needed, the dosage was titrated to 100 mg once daily in the morning or 100 mg, 300 mg, or 400 mg twice daily to achieve testosterone concentrations in the normal range . After the dosage titration period, patients continued their optimized dose for the remainder of the duration of the 6-month study. The mean duration of exposure was 168 days (range: 1 to 180 days). The median age was 52 years (range: 22 to 66 years); 77% were White, 19% were Black, 3% were Asian, and 2% were American Indian, Alaskan Native or Other.

Table 2 summarizes adverse reactions reported in ≥2% of patients in this 6-month study.

One (0.8%) patient who received KYZATREX® experienced an adverse reaction (acne) that lead to premature discontinuation from the study.

In a 12-month, open-label study in hypogonadal adult males (N=212) who received KYZATREX® 200 mg once daily to 400 mg twice daily (n=202) the following additional adverse reactions were reported: headache, arthralgia, diarrhea, hemoglobin increased, anxiety, constipation, peripheral edema, and PSA increased.

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KYZATREX® is not substitutable with other oral testosterone undecanoate products.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

KYZATREX® capsules are available in three strengths of 100 mg, 150 mg, and 200 mg packaged as 60, 90 and 120 units in wide-mouth, round, white HDPE bottles with white, polypropylene, child resistant caps and induction-sealed liner

100 mg: Oval, opaque, white capsules imprinted with "MP100" in red ink supplied in bottles; NDC 80603-101-11 for 90 capsules and NDC 80603-101-22 for 120 capsules.

150 mg: Oblong, opaque, white capsules imprinted with "MP150" in red ink supplied in bottles; NDC 80603-103-11 for 90 capsules and NDC 80603-103-22 for 120 capsules.

200 mg: Oblong, opaque, white capsules imprinted with "MP200" in red ink supplied in bottles; NDC 80603-105-33 for 60 capsules , NDC 80603-105-11 for 90 capsules and NDC 80603-105-22 for 120 capsules .

Individualize the dosage of KYZATREX® based on the patient's serum testosterone concentration response to the drug.

The recommended starting dose is 200 mg orally twice daily, once in the morning and once in the evening. Take KYZATREX® with food.

A 3-month repeat-dose oral toxicity study in male eugonadal dogs was conducted to evaluate whether phytosterol esters present in the KYZATREX® formulation influenced target organ toxicity due to their structural similarities to sex steroids like testosterone. KYZATREX® doses 2 times the MRHDD (based on mean AUC exposure to testosterone) produced similar effects on androgen-responsive tissues as testosterone undecanoate without phytosterol esters. These included mild to marked effects on the testes (decreased size, germ cell depletion, Leydig cell atrophy), epididymides (aspermia), adrenal glands (vacuolation in the zona fasciculata) and prostate (increased size and glandular hypertrophy/hyperplasia). Following a 4-week treatment-free period, findings in the testes, epididymides, and adrenal glands were not fully reversible at doses of 2 times the MRHDD of KYZATREX® as compared to treatment with the excipients alone, including phytosterol esters. Reversibility was not assessed in testosterone undecanoate groups without phytosterol esters.

Androgens, including KYZATREX®, may decrease concentrations of thyroxin-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.

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.

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With large doses of exogenous androgens, including KYZATREX®, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH, possibly leading to adverse effects on semen parameters including sperm count [see Use in Specific Populations (8.3) ]. Inform patients of this possible risk when deciding whether to use or to continue to use KYZATREX®.

Some prescription medications and nonprescription analgesic and cold medications contain drugs known to increase blood pressure. Concomitant administration of these medications with KYZATREX® may lead to additional increases in blood pressure [see Warnings and Precautions (5.4)].

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Prior to initiating KYZATRE®, 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.

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 [see Drug Abuse and Dependence (9)].

If testosterone abuse is suspected, check testosterone concentrations to ensure they are within therapeutic range [see Dosage and Administration ( 2.2)]. Testosterone levels may remain 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. Also consider the possibility of testosterone and anabolic androgenic steroid abuse in suspected patients who present with serious cardiovascular or psychiatric adverse events.

• Patients with BPH who are 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 prior to initiating and during treatment with androgens [see Contraindications (4)].