Tlando Drug Information

Important Dosage Information

TLANDO is not substitutable with other oral testosterone undecanoate products.

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.

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

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). 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 Hematocrit increased 6 Upper respiratory tract infection 5 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 Weight increased 2 Headache 2 Musculoskeletal pain 2 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 weeks of treatment with TLANDO. A total of 123 patients had acceptable 24-hour ABPM recordings at both time periods. In that group, the mean change in systolic BP from Baseline to End of Study was + 4.3 mmHg (95% CI 2.1, 6.5) and the mean change in diastolic BP was 1.4 mmHg (95% CI 0.5, 2.3). In patients with a history of hypertension at baseline, the mean ABPM systolic and diastolic blood pressure increased by 4.8 mmHg (95% CI 1.0, 8.5) and 1.6 mmHg (95% CI 0.1, 3.0), respectively (n=60). In patients with no history of hypertension at baseline systolic and diastolic blood pressure increased by 3.9 mmHg (95% CI 0.9, 6.8) and 1.2 mmHg (95% CI -0.1, 2.5), respectively (n =63). 2 patients (1.4 %) in the TLANDO safety set (n=138) either started new antihypertensive medications (n=2) or had their antihypertensive medication regimen adjusted (n=0) during Study 18-001. Of the 138 patients in Study 18-001 who used TLANDO, 7 patients (5.1%) were reported to have either an adverse reaction of hypertension (7 patients, 5.1%) or increased blood pressure (0 patients, 0.0%). Cardiovascular Outcomes TRAVERSE was a randomized, double-blind, cardiovascular outcomes study to assess the cardiovascular (CV) safety of topical testosterone gel compared to placebo in 5198 hypogonadal men aged 45 to 80 years with a history of CV disease or with multiple CV risk factors.

The primary outcome was the incidence of the composite endpoint of major adverse cardiovascular events (MACE), consisting of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. The mean duration of therapy was approximately 22 months. The mean duration of follow-up was 33 months.

Approximately 61% of all patients discontinued topical testosterone gel or placebo therapy. The mean patient age (±SD) was 63.3 years, with 2452 patients aged 65 years or more (47%), 2847 (about 55%) patients had pre-existing cardiovascular disease, whereas 2357 patients (about 45%) had an elevated cardiovascular risk at baseline, and mean BMI was 35 kg/m 2. Approximately 80% of patients were White, 17% were Black, and 3% were of other races or ethnic groups. Approximately 69%, 84%, and 93% had diabetes mellitus, hyperlipidemia, and hypertension, respectively.

The mean serum testosterone concentration at baseline in patients receiving topical testosterone gel was 220.4 ng/dL (n=2596). The mean serum testosterone concentrations at 12 months, 24 months, 36 months, and 48 months in patients receiving topical testosterone gel were 440.5 ng/dL (n=1683), 420.9 ng/dl (n=1125), 428.7 ng/dL (n=731), and 365.2 ng/dL (n=220), respectively. For patients treated with topical testosterone gel, the incidence of MACE was 7.0% (n=182 events) and for those receiving placebo, the incidence of MACE was 7.3% (n=190 events). The study demonstrated non-inferiority of topical testosterone gel versus placebo because the upper bound of 95% CI was less than the pre-specified risk margin, of 1.5 for MACE (Hazard Ratio 0.96 ). Additional Adverse Reactions Reported in TRAVERSE Additional adverse reactions reported in TRAVERSE at an incidence rate >2% in either treatment group and greater in topical testosterone gel versus placebo included: nonfatal arrythmias warranting intervention (5.2% vs 3.3%), atrial fibrillation (3.5% vs 2.4%), acute kidney injury (2.3% vs 1.5%) and bone fracture (3.5% vs 2.5%). For the adverse reaction of bone fracture, each event was adjudicated by clinical review. Increases in Hematocrit Increases in hematocrit were reported in 6 of the 138 patients (4.3%) in Study 18-001. None of these increases led to premature discontinuation of TLANDO. Increases in Prolactin Increases in serum prolactin were reported in 6 (6.3%) of the 95 patients in the 24-day clinical study.

The mean increase from baseline in serum prolactin was 7.0 ng/mL (n=93). The 4-month clinical study did not assess serum prolactin concentrations after the screening visit.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of testosterone replacement products. 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

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.

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.

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.

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 .

Pregnancy Risk Summary TLANDO is contraindicated in pregnant women and not indicated for use in females . 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 . 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.

Pediatric Use The safety and effectiveness of TLANDO 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.

is contraindicated in: Patients with carcinoma of the breast or known or suspected carcinoma of the prostate . Women who are pregnant. Testosterone can cause virilization of the female fetus when administered to a pregnant woman . Known hypersensitivity to testosterone undecanoate or any of TLANDO’s ingredients. Carcinoma of the breast or known or suspected carcinoma of the prostate Women who are pregnant.

Testosterone may cause fetal harm Hypersensitivity to TLANDO or any of its ingredients

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.