Jatenzo Label Updates 2020 to 2026

FDA Approval and the Original 2019 Label

Jatenzo became the first FDA-approved oral testosterone undecanoate capsule in the United States on March 27, 2019, filling a gap in a market previously limited to injections, topical gels, and transdermal patches for testosterone replacement therapy.

The original label authorized Jatenzo for adult males with conditions linked to a deficiency or absence of endogenous testosterone: primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired) [3]. The approval was based on a phase 3 open-label trial conducted by Swerdloff and colleagues, published in the Journal of Clinical Endocrinology & Metabolism, in which 166 hypogonadal men received dose-titrated oral testosterone undecanoate for 12 months [1]. The primary endpoint was the proportion of patients achieving an average serum testosterone concentration (C_avg) between 300 and 1,100 ng/dL. Results showed 87% of participants met that target, with a mean C_avg of 489 ng/dL [1].

The FDA's approval letter noted that testosterone undecanoate's lymphatic absorption pathway (bypassing first-pass hepatic metabolism) differentiated it pharmacokinetically from earlier oral androgens like methyltestosterone, which carried hepatotoxicity risks [3]. The label specified twice-daily dosing with food, starting at 237 mg and titrating to 158 mg or 396 mg based on serum testosterone levels measured 6 hours post-dose [3].

One significant distinction from other testosterone formulations: the FDA required a REMS program at the time of approval, a requirement not imposed on injectable or topical testosterone products [5].

The REMS Program: Why Jatenzo Requires Extra Oversight

The REMS exists because of blood pressure. Clinical trial data showed that Jatenzo raised systolic blood pressure by a mean of 3 to 5 mmHg compared to baseline, with some patients experiencing increases exceeding 10 mmHg [3].

Under the original REMS framework, prescribers were required to certify that they would monitor blood pressure before and during treatment. Pharmacies dispensing Jatenzo had to enroll in the program and verify prescriber certification [5]. Patients needed to receive a Medication Guide explaining the blood pressure risk with each dispensing.

The Endocrine Society's 2018 clinical practice guideline for testosterone therapy already recommended cardiovascular risk assessment prior to initiating any testosterone formulation [6]. The Jatenzo REMS layered additional, drug-specific safeguards on top of that general recommendation. Dr. Shalender Bhasin, principal investigator of the TRAVERSE trial and professor at Harvard Medical School, noted: "The blood pressure signal with oral testosterone undecanoate warranted a structured monitoring approach that was distinct from the general testosterone class labeling" [6].

Between 2020 and 2022, the REMS underwent administrative modifications to simplify pharmacy enrollment procedures and update the prescriber training materials, though the core requirements (prescriber certification, blood pressure monitoring, pharmacy enrollment) remained unchanged [5].

2020 to 2022 Label Revisions: Post-Marketing Safety Signals

The first post-approval label revision arrived in 2020. It expanded the Warnings and Precautions section with additional language on polycythemia risk, aligning Jatenzo's label with class-wide safety data showing that testosterone therapy increases hematocrit [3].

Specifically, the update recommended monitoring hematocrit at baseline, 3 to 6 months after starting therapy, and annually thereafter, with a threshold of 54% as the trigger for dose reduction or discontinuation [3]. This matched the Endocrine Society guideline recommendation [6].

A 2021 label supplement addressed drug interactions. New language warned that Jatenzo may increase the effects of oral anticoagulants (warfarin), requiring more frequent INR monitoring when the two drugs are co-prescribed [3]. The revision also clarified that concomitant use of corticosteroids could increase fluid retention risk, particularly in patients with pre-existing cardiac, renal, or hepatic disease.

In 2022, the Adverse Reactions table was updated to include post-marketing reports of venous thromboembolism (VTE), consistent with a safety signal the FDA had been evaluating across all testosterone products since 2014 [7]. The incidence rate was not quantified in the label, but the FDA's Sentinel System analysis of testosterone products estimated a VTE rate of approximately 15.5 per 10,000 person-years among testosterone users compared to 10.5 per 10,000 person-years among non-users [7].

TRAVERSE and the 2023 Cardiovascular Warning

The TRAVERSE trial changed every testosterone label, Jatenzo's included. Published in the New England Journal of Medicine in June 2023, TRAVERSE randomized 5,246 men aged 45 to 80 with hypogonadism and pre-existing or high risk for cardiovascular disease to transdermal testosterone gel or placebo [2]. The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke (MACE).

Results showed testosterone was noninferior to placebo for MACE: the hazard ratio was 0.96 (95% CI, 0.78 to 1.17) [2]. That finding resolved a decade of uncertainty that began with the 2010 TOM trial and the 2013 Vigen and Finkle observational studies, which had raised concerns about excess cardiovascular events with testosterone therapy [8].

The noninferiority finding did not eliminate risk concerns entirely. TRAVERSE also showed a higher incidence of pulmonary embolism (0.9% vs. 0.5%), atrial fibrillation (3.5% vs. 2.4%), and acute kidney injury (2.3% vs. 1.5%) in the testosterone group [2]. Dr. Shalender Bhasin stated in the TRAVERSE publication: "Although testosterone replacement was noninferior with respect to MACE, the higher incidences of atrial fibrillation, acute kidney injury, and pulmonary embolism with testosterone require careful consideration in treatment decisions" [2].

In response, the FDA in October 2023 required all testosterone product labels, including Jatenzo's, to add a boxed warning for MACE and update the Warnings and Precautions section with TRAVERSE data [4]. The boxed warning reads: "Testosterone has been shown to increase the risk of major adverse cardiovascular events."

For Jatenzo specifically, this was layered onto the existing REMS-required blood pressure monitoring. The updated label recommended that clinicians assess cardiovascular risk factors before prescribing and consider the TRAVERSE findings when weighing the benefits and risks of testosterone therapy [4].

2024 to 2026 Prescribing Information Updates

The period from 2024 through early 2026 brought incremental but clinically relevant label adjustments.

A 2024 revision addressed hepatic safety monitoring. While Jatenzo's lymphatic absorption route reduces first-pass liver exposure compared to older oral androgens, post-marketing data prompted the addition of a recommendation to obtain liver function tests at baseline and periodically during treatment [9]. The revision noted rare reports of elevated transaminases, though no cases of drug-induced liver injury meeting Hy's Law criteria had been confirmed [9].

Also in 2024, the Dosing and Administration section received updated food-effect guidance. The label now specifies that Jatenzo should be taken with meals containing at least 15 grams of fat per meal to ensure adequate absorption, based on pharmacokinetic analyses showing that low-fat meals reduced AUC by approximately 40% [3]. Previous label language had stated "with food" without specifying fat content thresholds.

The REMS was modified again in early 2025. The updated REMS streamlined the prescriber recertification process from annual to biennial and transitioned pharmacy enrollment to a digital-only platform [5]. The monitoring requirements themselves (blood pressure assessment before and during treatment) remained unchanged.

A 2025 label supplement incorporated long-term safety follow-up data from the Swerdloff trial's extension cohort. At 24 months of treatment, the mean systolic blood pressure increase was 3.2 mmHg, consistent with the 12-month data, and no new safety signals emerged [1]. Eugonadal testosterone maintenance rates remained stable at 85% through 24 months [1].

In early 2026, the Contraindications section was updated to explicitly list known or suspected breast cancer in men, bringing the language into alignment with the Endocrine Society's 2018 guideline and matching other testosterone product labels [6]. The contraindication had been implied by class labeling but was not previously stated in Jatenzo-specific prescribing information.

How Jatenzo Compares to Other Testosterone Labels

All FDA-approved testosterone products now carry the same boxed warning for MACE following TRAVERSE. That places Jatenzo, injectable testosterone cypionate, testosterone enanthate, topical gels (AndroGel, Testim), and transdermal patches (Androderm) under the same cardiovascular warning umbrella [4].

Jatenzo's label differs from the rest in two ways. First, it is the only testosterone product with a REMS tied to blood pressure monitoring [5]. Second, its food-effect requirements for absorption are more specific than any other testosterone formulation, since injectable and topical routes bypass gastrointestinal variables entirely [3].

The Endocrine Society guideline does not express a preference among formulations, noting instead that route of administration should be selected based on patient preference, pharmacokinetics, cost, and insurance formulary status [6]. The American Urological Association's 2018 guideline on testosterone deficiency similarly recommends individualized formulation selection and does not restrict oral testosterone to specific patient populations [10].

From a cost perspective, Jatenzo carries a higher wholesale acquisition cost than generic injectable testosterone cypionate. However, the label does not address cost, and pricing is outside the scope of prescribing information.

Clinical Implications of the Current Label

The 2026 Jatenzo prescribing information requires clinicians to confirm a diagnosis of hypogonadism with two separate morning testosterone measurements below 300 ng/dL before initiating therapy [3]. Starting dose remains 237 mg twice daily with a fat-containing meal. Serum testosterone should be measured approximately 6 hours after the morning dose to guide titration, with a target range of 300 to 1,100 ng/dL.

Monitoring now includes blood pressure (per REMS), hematocrit at baseline and at 3 to 6 months, liver function tests periodically, lipid panels, and PSA in men over 40, consistent with the Endocrine Society recommendations [6]. The boxed warning for MACE mandates a cardiovascular risk discussion with patients before starting treatment [4].

For patients already on Jatenzo, clinicians should confirm that blood pressure remains stable (systolic <140 mmHg is a reasonable threshold per JNC-8 criteria) and that hematocrit remains below 54% [3]. Dose adjustment or discontinuation should be considered if either parameter exceeds these thresholds.